Picolinamide compounds with fungicidal activity

Abstract

This disclosure relates to picolinamides of Formula I and their use as fungicides. ##STR00001##

Claims

1. A compound selected from: ##STR00578## ##STR00579##

2. A compound selected from: ##STR00580##

3. A compound of the formula: ##STR00581## produced from either of the following chemical reactions: ##STR00582## wherein: a is treatment of compound 9.0 with a suspension of a copper(I) salt and 4-fluoro-phenylmagnesium bromide in a polar aprotic solvent; b is treatment of compound 6.1 with a hydride reagent in the presence of a catalyst; and R.sub.3 and R.sub.12 are both 4-fluorophenyl.

Description

DETAILED DESCRIPTION

(1) The compounds of the present disclosure may be applied by any of a variety of known techniques, either as the compounds or as formulations comprising the compounds. For example, the compounds may be applied to the roots or foliage of plants for the control of various fungi, without damaging the commercial value of the plants. The materials may be applied in the form of any of the generally used formulation types, for example, as solutions, dusts, wettable powders, flowable concentrate, or emulsifiable concentrates.

(2) Preferably, the compounds of the present disclosure are applied in the form of a formulation, comprising one or more of the compounds of Formula I with a phytologically acceptable carrier. Concentrated formulations may be dispersed in water, or other liquids, for application, or formulations may be dust-like or granular, which may then be applied without further treatment. The formulations can be prepared according to procedures that are conventional in the agricultural chemical art.

(3) The present disclosure contemplates all vehicles by which one or more of the compounds may be formulated for delivery and use as a fungicide. Typically, formulations are applied as aqueous suspensions or emulsions. Such suspensions or emulsions may be produced from water-soluble, water-suspendible, or emulsifiable formulations which are solids, usually known as wettable powders; or liquids, usually known as emulsifiable concentrates, aqueous suspensions, or suspension concentrates. As will be readily appreciated, any material to which these compounds may be added may be used, provided it yields the desired utility without significant interference with the activity of these compounds as antifungal agents.

(4) Wettable powders, which may be compacted to form water-dispersible granules, comprise an intimate mixture of one or more of the compounds of Formula I, an inert carrier and surfactants. The concentration of the compound in the wettable powder may be from about 10 percent to about 90 percent by weight based on the total weight of the wettable powder, more preferably about 25 weight percent to about 75 weight percent. In the preparation of wettable powder formulations, the compounds may be compounded with any finely divided solid, such as prophyllite, talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clays, diatomaceous earths, purified silicates or the like. In such operations, the finely divided carrier and surfactants are typically blended with the compound(s) and milled.

(5) Emulsifiable concentrates of the compounds of Formula I may comprise a convenient concentration, such as from about 1 weight percent to about 50 weight percent of the compound, in a suitable liquid, based on the total weight of the concentrate. The compounds may be dissolved in an inert carrier, which is either a water-miscible solvent or a mixture of water-immiscible organic solvents, and emulsifiers. The concentrates may be diluted with water and oil to form spray mixtures in the form of oil-in-water emulsions. Useful organic solvents include aromatics, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, for example, terpenic solvents, including rosin derivatives, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2-ethoxyethanol.

(6) Emulsifiers which may be advantageously employed herein may be readily determined by those skilled in the art and include various nonionic, anionic, cationic and amphoteric emulsifiers, or a blend of two or more emulsifiers. Examples of nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene. Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts. Anionic emulsifiers include the oil-soluble salts (e.g., calcium) of alkylaryl sulfonic acids, oil-soluble salts or sulfated polyglycol ethers and appropriate salts of phosphated polyglycol ether.

(7) Representative organic liquids which may be employed in preparing the emulsifiable concentrates of the compounds of the present disclosure are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, the methyl ether of triethylene glycol, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; vegetable oils such as soybean oil, rapeseed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of the above vegetable oils; and the like. Mixtures of two or more organic liquids may also be employed in the preparation of the emulsifiable concentrate. Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases. Surface-active dispersing agents are typically employed in liquid formulations and in an amount of from 0.1 to 20 percent by weight based on the combined weight of the dispersing agent with one or more of the compounds. The formulations can also contain other compatible additives, for example, plant growth regulators and other biologically active compounds used in agriculture.

(8) Aqueous suspensions comprise suspensions of one or more water-insoluble compounds of Formula I, dispersed in an aqueous vehicle at a concentration in the range from about 1 to about 50 weight percent, based on the total weight of the aqueous suspension. Suspensions are prepared by finely grinding one or more of the compounds, and vigorously mixing the ground material into a vehicle comprised of water and surfactants chosen from the same types discussed above. Other components, such as inorganic salts and synthetic or natural gums, may also be added to increase the density and viscosity of the aqueous vehicle.

(9) The compounds of Formula I can also be applied as granular formulations, which are particularly useful for applications to the soil. Granular formulations generally contain from about 0.5 to about 10 weight percent, based on the total weight of the granular formulation of the compound(s), dispersed in an inert carrier which consists entirely or in large part of coarsely divided inert material such as attapulgite, bentonite, diatomite, clay or a similar inexpensive substance. Such formulations are usually prepared by dissolving the compounds in a suitable solvent and applying it to a granular carrier which has been preformed to the appropriate particle size, in the range of from about 0.5 to about 3 mm. A suitable solvent is a solvent in which the compound is substantially or completely soluble. Such formulations may also be prepared by making a dough or paste of the carrier and the compound and solvent, and crushing and drying to obtain the desired granular particle.

(10) Dusts containing the compounds of Formula I may be prepared by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.

(11) The formulations may additionally contain adjuvant surfactants to enhance deposition, wetting, and penetration of the compounds onto the target crop and organism. These adjuvant surfactants may optionally be employed as a component of the formulation or as a tank mix. The amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume, based on a spray-volume of water, preferably 0.05 to 0.5 volume percent. Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulfosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines, blends of surfactants with mineral or vegetable oils, crop oil concentrate (mineral oil (85%)+emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C.sub.9-C.sub.11 alkylpolyglycoside; phosphated alcohol ethoxylate; natural primary alcohol (C.sub.12-C.sub.16) ethoxylate; di-sec-butylphenol EO-PO block copolymer; polysiloxane-methyl cap; nonylphenol ethoxylate+urea ammonium nitrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate (8EO); tallow amine ethoxylate (15 EO); PEG(400) dioleate-99. The formulations may also include oil-in-water emulsions such as those disclosed in U.S. patent application Ser. No. 11/495,228, the disclosure of which is expressly incorporated by reference herein.

(12) The formulations may optionally include combinations that contain other pesticidal compounds. Such additional pesticidal compounds may be fungicides, insecticides, herbicides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds. Accordingly, in such embodiments, the other pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use. The compounds of Formula I and the pesticidal compound in the combination can generally be present in a weight ratio of from 1:100 to 100:1.

(13) The compounds of the present disclosure may also be combined with other fungicides to form fungicidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure are often applied in conjunction with one or more other fungicides to control a wider variety of undesirable diseases. When used in conjunction with other fungicide(s), the presently claimed compounds may be formulated with the other fungicide(s), tank-mixed with the other fungicide(s) or applied sequentially with the other fungicide(s). Such other fungicides may include 2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol, 8-hydroxyquinoline sulfate, ametoctradin, amisulbrom, antimycin, Ampelomyces quisqualis, azaconazole, azoxystrobin, Bacillus subtilis, Bacillus subtilis strain QST713, benalaxyl, benomyl, benthiavalicarb-isopropyl, benzovindiflupyr, benzylaminobenzene-sulfonate (BABS) salt, bicarbonates, biphenyl, bismerthiazol, bitertanol, bixafen, blasticidin-S, borax, Bordeaux mixture, boscalid, bromuconazole, bupirimate, calcium polysulfide, captafol, captan, carbendazim, carboxin, carpropamid, carvone, chlazafenone, chloroneb, chlorothalonil, chlozolinate, Coniothyrium minitans, copper hydroxide, copper octanoate, copper oxychloride, copper sulfate, copper sulfate (tribasic), coumoxystrobin, cuprous oxide, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dazomet, debacarb, diammonium ethylenebis-(dithiocarbamate), dichlofluanid, dichlorophen, diclocymet, diclomezine, dichloran, diethofencarb, difenoconazole, difenzoquat ion, diflumetorim, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinobuton, dinocap, diphenylamine, dipymetitrone, dithianon, dodemorph, dodemorph acetate, dodine, dodine free base, edifenphos, enestrobin, enestroburin, enoxastrobin, epoxiconazole, ethaboxam, ethoxyquin, etridiazole, famoxadone, fenamidone, fenaminostrobin, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flufenoxystrobin, flumorph, fluopicolide, fluopyram, fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, fluxapyroxad, folpet, formaldehyde, fosetyl, fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, guazatine, guazatine acetates, GY-81, hexachlorobenzene, hexaconazole, hymexazol, imazalil, imazalil sulfate, imibenconazole, iminoctadine, iminoctadine triacetate, iminoctadine tris(albesilate), iodocarb, ipconazole, ipfenpyrazolone, iprobenfos, iprodione, iprovalicarb, isofetamid, isoprothiolane, isopyrazam, isotianil, kasugamycin, kasugamycin hydrochloride hydrate, kresoxim-methyl, laminarin, mancopper, mancozeb, mandestrobin, mandipropamid, maneb, mefenoxam, mepanipyrim, mepronil, meptyl-dinocap, mercuric chloride, mercuric oxide, mercurous chloride, metalaxyl, metalaxyl-M, metam, metam-ammonium, metam-potassium, metam-sodium, metconazole, methasulfocarb, methyl iodide, methyl isothiocyanate, metiram, metominostrobin, metrafenone, mildiomycin, myclobutanil, nabam, nitrothal-isopropyl, nuarimol, octhilinone, ofurace, oleic acid (fatty acids), orysastrobin, oxadixyl, oxathiapiprolin, oxine-copper, oxpoconazole fumarate, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen, pentachlorophenol, pentachlorophenyl laurate, penthiopyrad, phenylmercury acetate, phosphonic acid, phthalide, picarbutrazox, picoxystrobin, polyoxin B, polyoxins, polyoxorim, potassium bicarbonate, potassium hydroxyquinoline sulfate, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, proquinazid, prothioconazole, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyraziflumid, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyrisoxazole, pyroquilon, quinoclamine, quinoxyfen, quintozene, Reynoutria sachalinensis extract, sedaxane, silthiofam, simeconazole, sodium 2-phenylphenoxide, sodium bicarbonate, sodium pentachlorophenoxide, spiroxamine, sulfur, SYP-Z048, tar oils, tebuconazole, tebufloquin, tecnazene, tetraconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolprocarb, tolylfluanid, triadimefon, triadimenol, triazoxide, triclopyricarb, tricyclazole, tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, validamycin, valifenalate, valiphenal, vinclozolin, zineb, ziram, zoxamide, Candida oleophila, Fusarium oxysporum, Gliocladium spp., Phlebiopsis gigantea, Streptomyces griseoviridis, Trichoderma spp., (RS)—N-(3,5-dichlorophenyl)-2-(methoxymethyl)-succinimide, 1,2-dichloropropane, 1,3-dichloro-1,1,3,3-tetrafluoroacetone hydrate, 1-chloro-2,4-dinitronaphthalene, 1-chloro-2-nitropropane, 2-(2-heptadecyl-2-imidazolin-1-yl)ethanol, 2,3-dihydro-5-phenyl-1,4-dithi-ine 1,1,4,4-tetraoxide, 2-methoxyethylmercury acetate, 2-methoxyethylmercury chloride, 2-methoxyethylmercury silicate, 3-(4-chlorophenyl)-5-methylrhodanine, 4-(2-nitroprop-1-enyl)phenyl thiocyanateme, ampropylfos, anilazine, azithiram, barium polysulfide, Bayer 32394, benodanil, benquinox, bentaluron, benzamacril, benzamacril-isobutyl, benzamorf, binapacryl, bis(methylmercury) sulfate, bis(tributyltin) oxide, buthiobate, cadmium calcium copper zinc chromate sulfate, carbamorph, CECA, chlobenthiazone, chloraniformethan, chlorfenazole, chlorquinox, climbazole, copper bis(3-phenylsalicylate), copper zinc chromate, cufraneb, cupric hydrazinium sulfate, cuprobam, cyclafuramid, cypendazole, cyprofuram, decafentin, dichlone, dichlozoline, diclobutrazol, dimethirimol, dinocton, dinosulfon, dinoterbon, dipyrithione, ditalimfos, dodicin, drazoxolon, EBP, ESBP, etaconazole, etem, ethirim, fenaminosulf, fenapanil, fenitropan, fluotrimazole, furcarbanil, furconazole, furconazole-cis, furmecyclox, furophanate, glyodine, griseofulvin, halacrinate, Hercules 3944, hexylthiofos, ICIA0858, isopamphos, isovaledione, mebenil, mecarbinzid, metazoxolon, methfuroxam, methylmercury dicyandiamide, metsulfovax, milneb, mucochloric anhydride, myclozolin, N-3,5-dichlorophenyl-succinimide, N-3-nitrophenylitaconimide, natamycin, N-ethylmercurio-4-toluenesulfonanilide, nickel bis(dimethyldithiocarbamate), OCH, phenylmercury dimethyldithiocarbamate, phenylmercury nitrate, phosdiphen, prothiocarb, prothiocarb hydrochloride, pyracarbolid, pyridinitril, pyroxychlor, pyroxyfur, quinacetol, quinacetol sulfate, quinazamid, quinconazole, rabenzazole, salicylanilide, SSF-109, sultropen, tecoram, thiadifluor, thicyofen, thiochlorfenphim, thiophanate, thioquinox, tioxymid, triamiphos, triarimol, triazbutil, trichlamide, urbacid, zarilamid, and any combinations thereof.

(14) Additionally, the compounds described herein may be combined with other pesticides, including insecticides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure may be applied in conjunction with one or more other pesticides to control a wider variety of undesirable pests. When used in conjunction with other pesticides, the presently claimed compounds may be formulated with the other pesticide(s), tank-mixed with the other pesticide(s) or applied sequentially with the other pesticide(s). Typical insecticides include, but are not limited to: 1,2-dichloropropane, abamectin, acephate, acetamiprid, acethion, acetoprole, acrinathrin, acrylonitrile, afidopyropen, alanycarb, aldicarb, aldoxycarb, aldrin, allethrin, allosamidin, allyxycarb, alpha-cypermethrin, alpha-ecdysone, alpha-endosulfan, amidithion, aminocarb, amiton, amiton oxalate, amitraz, anabasine, athidathion, azadirachtin, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, barium hexafluorosilicate, barthrin, bendiocarb, benfuracarb, bensultap, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bistrifluron, borax, boric acid, broflanilide, bromfenvinfos, bromocyclen, bromo-DDT, bromophos, bromophos-ethyl, bufencarb, buprofezin, butacarb, butathiofos, butocarboxim, butonate, butoxycarboxim, cadusafos, calcium arsenate, calcium polysulfide, camphechlor, carbanolate, carbaryl, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, cartap, cartap hydrochloride, chlorantraniliprole, chlorbicyclen, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorethoxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, chloroform, chloropicrin, chlorphoxim, chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, chromafenozide, cinerin I, cinerin II, cinerins, cismethrin, clacyfos, cloethocarb, closantel, clothianidin, copper acetoarsenite, copper arsenate, copper naphthenate, copper oleate, coumaphos, coumithoate, crotamiton, crotoxyphos, crufomate, cryolite, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyclaniliprole, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin, cyromazine, cythioate, DDT, decarbofuran, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, diafenthiuron, dialifos, diatomaceous earth, diazinon, dicapthon, dichlofenthion, dichlorvos, dicloromezotiaz, dicresyl, dicrotophos, dicyclanil, dieldrin, diflubenzuron, dilor, dimefluthrin, dimefox, dimetan, dimethoate, dimethrin, dimethylvinphos, dimetilan, dinex, dinex-diclexine, dinoprop, dinosam, dinotefuran, diofenolan, dioxabenzofos, dioxacarb, dioxathion, disulfoton, dithicrofos, d-limonene, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, doramectin, ecdysterone, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothion, endrin, EPN, epofenonane, eprinomectin, esdepallethrine, esfenvalerate, etaphos, ethiofencarb, ethion, ethiprole, ethoate-methyl, ethoprophos, ethyl formate, ethyl-DDD, ethylene dibromide, ethylene dichloride, ethylene oxide, etofenprox, etrimfos, EXD, famphur, fenamiphos, fenazaflor, fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, fenobucarb, fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin, fensulfothion, fenthion, fenthion-ethyl, fenvalerate, fipronil, flometoquin, flonicamid, flubendiamide, flucofuron, flucycloxuron, flucythrinate, flufenerim, flufenoxuron, flufenprox, flufiprole, fluhexafon, flupyradifurone, fluvalinate, fonofos, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosmethilan, fospirate, fosthietan, furathiocarb, furethrin, gamma-cyhalothrin, gamma-HCH, halfenprox, halofenozide, HCH, HEOD, heptachlor, heptafluthrin, heptenophos, heterophos, hexaflumuron, HHDN, hydramethylnon, hydrogen cyanide, hydroprene, hyquincarb, imidacloprid, imiprothrin, indoxacarb, iodomethane, IPSP, isazofos, isobenzan, isocarbophos, isodrin, isofenphos, isofenphos-methyl, isoprocarb, isoprothiolane, isothioate, isoxathion, ivermectin, jasmolin I, jasmolin II, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kappa-bifenthrin, kappa-tefluthrin, kelevan, kinoprene, lambda-cyhalothrin, lead arsenate, lepimectin, leptophos, lindane, lirimfos, lufenuron, lythidathion, malathion, malonoben, mazidox, mecarbam, mecarphon, menazon, mephosfolan, mercurous chloride, mesulfenfos, metaflumizone, methacrifos, methamidophos, methidathion, methiocarb, methocrotophos, methomyl, methoprene, methoxychlor, methoxyfenozide, methyl bromide, methyl isothiocyanate, methylchloroform, methylene chloride, metofluthrin, metolcarb, metoxadiazone, mevinphos, mexacarbate, milbemectin, milbemycin oxime, mipafox, mirex, molosultap, momfluorothrin, monocrotophos, monomehypo, monosultap, morphothion, moxidectin, naftalofos, naled, naphthalene, nicotine, nifluridide, nitenpyram, nithiazine, nitrilacarb, novaluron, noviflumuron, omethoate, oxamyl, oxydemeton-methyl, oxydeprofos, oxydisulfoton, para-dichlorobenzene, parathion, parathion-methyl, penfluron, pentachlorophenol, permethrin, phenkapton, phenothrin, phenthoate, phorate, phosalone, phosfolan, phosmet, phosnichlor, phosphamidon, phosphine, phoxim, phoxim-methyl, pirimetaphos, pirimicarb, pirimiphos-ethyl, pirimiphos-methyl, potassium arsenite, potassium thiocyanate, pp′-DDT, prallethrin, precocene I, precocene II, precocene II, primidophos, profenofos, profluralin, promacyl, promecarb, propaphos, propetamphos, propoxur, prothidathion, prothiofos, prothoate, protrifenbute, pyflubumide, pyraclofos, pyrafluprole, pyrazophos, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyridaben, pyridalyl, pyridaphenthion, pyrifluquinazon, pyrimidifen, pyriminostrobin, pyrimitate, pyriprole, pyriproxyfen, quassia, quinalphos, quinalphos-methyl, quinothion, rafoxanide, resmethrin, rotenone, ryania, sabadilla, schradan, selamectin, silafluofen, silica gel, sodium arsenite, sodium fluoride, sodium hexafluorosilicate, sodium thiocyanate, sophamide, spinetoram, spinosad, spiromesifen, spirotetramat, sulcofuron, sulcofuron-sodium, sulfluramid, sulfotep, sulfoxaflor, sulfuryl fluoride, sulprofos, tau-fluvalinate, tazimcarb, TDE, tebufenozide, tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin, temephos, TEPP, terallethrin, terbufos, tetrachloroethane, tetrachlorvinphos, tetramethrin, tetramethylfluthrin, tetraniliprole, theta-cypermethrin, thiacloprid, thiamethoxam, thicrofos, thiocarboxime, thiocyclam, thiocyclam oxalate, thiodicarb, thiofanox, thiometon, thiosultap, thiosultap-disodium, thiosultap-monosodium, thuringiensin, tioxazafen, tolfenpyrad, tralomethrin, transfluthrin, transpermethrin, triarathene, triazamate, triazophos, trichlorfon, trichlormetaphos-3, trichloronat, trifenofos, triflumezopyrim, triflumuron, trimethacarb, triprene, vamidothion, vaniliprole, XMC, xylylcarb, zeta-cypermethrin, zolaprofos, and any combinations thereof.

(15) Additionally, the compounds described herein may be combined with herbicides that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure may be applied in conjunction with one or more herbicides to control a wide variety of undesirable plants. When used in conjunction with herbicides, the presently claimed compounds may be formulated with the herbicide(s), tank-mixed with the herbicide(s) or applied sequentially with the herbicide(s). Typical herbicides include, but are not limited to: 4-CPA; 4-CPB; 4-CPP; 2,4-D; 3,4-DA; 2,4-DB; 3,4-DB; 2,4-DEB; 2,4-DEP; 3,4-DP; 2,3,6-TBA; 2,4,5-T; 2,4,5-TB; acetochlor, acifluorfen, aclonifen, acrolein, alachlor, allidochlor, alloxydim, allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidosulfuron, aminocyclopyrachlor, aminopyralid, amiprofos-methyl, amitrole, ammonium sulfamate, anilofos, anisuron, asulam, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC, beflubutamid, benazolin, bencarbazone, benfluralin, benfuresate, bensulfuron, bensulide, bentazone, benzadox, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzoylprop, benzthiazuron, bicyclopyrone, bifenox, bilanafos, bispyribac, borax, bromacil, bromobonil, bromobutide, bromofenoxim, bromoxynil, brompyrazon, butachlor, butafenacil, butamifos, butenachlor, buthidazole, buthiuron, butralin, butroxydim, buturon, butylate, cacodylic acid, cafenstrole, calcium chlorate, calcium cyanamide, cambendichlor, carbasulam, carbetamide, carboxazole, chlorprocarb, carfentrazone, CDEA, CEPC, chlomethoxyfen, chloramben, chloranocryl, chlorazifop, chlorazine, chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenprop, chlorflurazole, chlorflurenol, chloridazon, chlorimuron, chlornitrofen, chloropon, chlorotoluron, chloroxuron, chloroxynil, chlorpropham, chlorsulfuron, chlorthal, chlorthiamid, cinidon-ethyl, cinmethylin, cinosulfuron, cisanilide, clethodim, cliodinate, clodinafop, clofop, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, cloransulam, CMA, copper sulfate, CPMF, CPPC, credazine, cresol, cumyluron, cyanatryn, cyanazine, cycloate, cyclopyrimorate, cyclosulfamuron, cycloxydim, cycluron, cyhalofop, cyperquat, cyprazine, cyprazole, cypromid, daimuron, dalapon, dazomet, delachlor, desmedipham, desmetryn, di-allate, dicamba, dichlobenil, dichloralurea, dichlormate, dichlorprop, dichlorprop-P, diclofop, diclosulam, diethamquat, diethatyl, difenopenten, difenoxuron, difenzoquat, diflufenican, diflufenzopyr, dimefuron, dimepiperate, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimexano, dimidazon, dinitramine, dinofenate, dinoprop, dinosam, dinoseb, dinoterb, diphenamid, dipropetryn, diquat, disul, dithiopyr, diuron, DMPA, DNOC, DSMA, EBEP, eglinazine, endothal, epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethametsulfuron, ethidimuron, ethiolate, ethofumesate, ethoxyfen, ethoxysulfuron, etinofen, etnipromid, etobenzanid, EXD, fenasulam, fenoprop, fenoxaprop, fenoxaprop-P, fenoxasulfone, fenquinotrione, fenteracol, fenthiaprop, fentrazamide, fenuron, ferrous sulfate, flamprop, flamprop-M, flazasulfuron, florasulam, fluazifop, fluazifop-P, fluazolate, flucarbazone, flucetosulfuron, fluchloralin, flufenacet, flufenican, flufenpyr, flumetsulam, flumezin, flumiclorac, flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen, fluoromidine, fluoronitrofen, fluothiuron, flupoxam, flupropacil, flupropanate, flupyrsulfuron, fluridone, flurochloridone, fluroxypyr, flurtamone, fluthiacet, fomesafen, foramsulfuron, fosamine, furyloxyfen, glufosinate, glufosinate-P, glyphosate, halauxifen, halosafen, halosulfuron, haloxydine, haloxyfop, haloxyfop-P, hexachloroacetone, hexaflurate, hexazinone, imazamethabenz, imazamox, imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, indanofan, indaziflam, iodobonil, iodomethane, iodosulfuron, iofensulfuron, ioxynil, ipazine, ipfencarbazone, iprymidam, isocarbamid, isocil, isomethiozin, isonoruron, isopolinate, isopropalin, isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole, isoxapyrifop, karbutilate, ketospiradox, lactofen, lenacil, linuron, MAA, MAMA, MCPA, MCPA-thioethyl, MCPB, mecoprop, mecoprop-P, medinoterb, mefenacet, mefluidide, mesoprazine, mesosulfuron, mesotrione, metam, metamifop, metamitron, metazachlor, metazosulfuron, metflurazon, methabenzthiazuron, methalpropalin, methazole, methiobencarb, methiozolin, methiuron, methometon, methoprotryne, methyl bromide, methyl isothiocyanate, methyldymron, metobenzuron, metobromuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, molinate, monalide, monisouron, monochloroacetic acid, monolinuron, monuron, morfamquat, MSMA, naproanilide, napropamide, napropamide-M, naptalam, neburon, nicosulfuron, nipyraclofen, nitralin, nitrofen, nitrofluorfen, norflurazon, noruron, OCH, orbencarb, ortho-dichlorobenzene, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon, oxasulfuron, oxaziclomefone, oxyfluorfen, parafluron, paraquat, pebulate, pelargonic acid, pendimethalin, penoxsulam, pentachlorophenol, pentanochlor, pentoxazone, perfluidone, pethoxamid, phenisopham, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenylmercury acetate, picloram, picolinafen, pinoxaden, piperophos, potassium arsenite, potassium azide, potassium cyanate, pretilachlor, primisulfuron, procyazine, prodiamine, profluazol, profluralin, profoxydim, proglinazine, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham, propisochlor, propoxycarbazone, propyrisulfuron, propyzamide, prosulfalin, prosulfocarb, prosulfuron, proxan, prynachlor, pydanon, pyraclonil, pyraflufen, pyrasulfotole, pyrazolynate, pyrazosulfuron, pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridate, pyriftalid, pyriminobac, pyrimisulfan, pyrithiobac, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quinoclamine, quinonamid, quizalofop, quizalofop-P, rhodethanil, rimsulfuron, saflufenacil, S-metolachlor, sebuthylazine, secbumeton, sethoxydim, siduron, simazine, simeton, simetryn, SMA, sodium arsenite, sodium azide, sodium chlorate, sulcotrione, sulfallate, sulfentrazone, sulfometuron, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA, tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim, terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, terbutryn, tetrafluron, thenylchlor, thiazafluron, thiazopyr, thidiazimin, thidiazuron, thiencarbazone-methyl, thifensulfuron, thiobencarb, tiafenacil, tiocarbazil, tioclorim, tolpyralate, topramezone, tralkoxydim, triafamone, tri-allate, triasulfuron, triaziflam, tribenuron, tricamba, triclopyr, tridiphane, trietazine, trifloxysulfuron, trifludimoxazin, trifluralin, triflusulfuron, trifop, trifopsime, trihydroxytriazine, trimeturon, tripropindan, tritac, tritosulfuron, vernolate, and xylachlor.

(16) Another embodiment of the present disclosure is a method for the control or prevention of fungal attack. This method comprises applying to the soil, plant, roots, foliage, or locus of the fungus, or to a locus in which the infestation is to be prevented (for example applying to cereal or grape plants), a fungicidally effective amount of one or more of the compounds of Formula I. The compounds are suitable for treatment of various plants at fungicidal levels, while exhibiting low phytotoxicity. The compounds may be useful both in a protectant and/or an eradicant fashion.

(17) The compounds have been found to have significant fungicidal effect particularly for agricultural use. Many of the compounds are particularly effective for use with agricultural crops and horticultural plants.

(18) It will be understood by those skilled in the art that the efficacy of the compound for the foregoing fungi establishes the general utility of the compounds as fungicides.

(19) The compounds have broad ranges of activity against fungal pathogens. Exemplary pathogens may include, but are not limited to, causing agent of wheat leaf blotch (Zymoseptoria tritici), wheat brown rust (Puccinia triticina), wheat stripe rust (Puccinia striiformis), scab of apple (Venturia inaequalis), powdery mildew of grapevine (Uncinula necator), barley scald (Rhynchosporium secalis), blast of rice (Pyricularia oryzae), rust of soybean (Phakopsora pachyrhizi), glume blotch of wheat (Leptosphaeria nodorum), powdery mildew of wheat (Blumeria graminis f. sp. tritici), powdery mildew of barley (Blumeria graminis f. sp. hordei), powdery mildew of cucurbits (Erysiphe cichoracearum), anthracnose of cucurbits (Colletotrichum lagenarium), leaf spot of beet (Cercospora beticola), early blight of tomato (Alternaria solani), and spot blotch of barley (Cochliobolus sativus). The exact amount of the active material to be applied is dependent not only on the specific active material being applied, but also on the particular action desired, the fungal species to be controlled, and the stage of growth thereof, as well as the part of the plant or other product to be contacted with the compound. Thus, all the compounds, and formulations containing the same, may not be equally effective at similar concentrations or against the same fungal species.

(20) The compounds are effective in use with plants in a disease-inhibiting and phytologically acceptable amount. The term “disease-inhibiting and phytologically acceptable amount” refers to an amount of a compound that kills or inhibits the plant disease for which control is desired, but is not significantly toxic to the plant. This amount will generally be from about 0.1 to about 1000 ppm (parts per million), with 1 to 500 ppm being preferred. The exact concentration of compound required varies with the fungal disease to be controlled, the type of formulation employed, the method of application, the particular plant species, climate conditions, and the like. A suitable application rate is typically in the range from about 0.10 to about 4 pounds/acre (about 0.01 to 0.45 grams per square meter, g/m.sup.2).

(21) Any range or desired value given herein may be extended or altered without losing the effects sought, as is apparent to the skilled person for an understanding of the teachings herein.

(22) The compounds of Formula I may be made using well-known chemical procedures.

(23) Intermediates not specifically mentioned in this disclosure are either commercially available, may be made by routes disclosed in the chemical literature, or may be readily synthesized from commercial starting materials utilizing standard procedures.

General Schemes

(24) The following schemes illustrate approaches to generating picolinamide compounds of Formula I. The following descriptions and examples are provided for illustrative purposes and should not be construed as limiting in terms of substituents or substitution patterns.

(25) Compounds of Formula 1.1, wherein R.sub.3 and R.sub.12 are as originally defined and are equivalent, can be prepared by the methods shown in Scheme 1, step a. The compound of Formula 1.0 can be treated with an organometallic nucleophile such as phenylmagnesium bromide (PhMgBr) in a polar aprotic solvent such as tetrahydrofuran (THF) at a temperature of about 0° C. to 23° C. to afford compounds of Formula 1.1, wherein R.sub.3 and R.sub.12 are as previously defined, as shown in a.

(26) ##STR00004##

(27) Compounds of Formula 2.2, wherein R.sub.3 is as originally defined and may or may not be equal to R.sub.12, can be prepared by the methods shown in Scheme 2, steps a-c. Compounds of Formula 2.2, wherein R.sub.3 and R.sub.12 are as previously defined but not an electron-deficient aryl or heteroaryl group and may or may not be equivalent, can be obtained by treating the compounds of Formula 2.0, wherein R.sub.3 and R.sub.12 are as previously defined but not an electron-deficient aryl or heteroaryl group and may or may not be equivalent, with a mixture of a hydride reagent, such as triethylsilane (Et.sub.3SiH), and an acid, such as 2,2,2-trifluoroacetic acid (TFA) in a halogenated solvent such as dichloromethane (DCM) at a temperature of about 0° C. to 23° C., as depicted in a. Alternatively, compounds of Formula 2.1, wherein R.sub.3 and R.sub.12 are an electron-deficient aryl or heteroaryl group and may or may not be equivalent, can be obtained by treating the compounds of Formula 2.0, wherein R.sub.3 and R.sub.12 are an electron-deficient aryl or heteroaryl group and may or may not be equivalent, with a base, such as sodium hydride (NaH), and a catalyst, such as imidazole, in a polar aprotic solvent such as THF at a temperature of about 23° C., followed by sequential addition of carbon disulfide (CS.sub.2) and an alkyl iodide, such as iodomethane (Mel), as depicted in b. Compounds of Formula 2.2, wherein R.sub.3 and R.sub.12 are an electron-deficient aryl or heteroaryl group and may or may not be equivalent, can be obtained by treating the compounds of Formula 2.1, wherein R.sub.3 and R.sub.12 are as previously defined and may or may not be equivalent, with a tin reagent, such as tributyltin hydride, and a radical initiator, such as azobisisobutyronitrile (AIBN), in a nonpolar solvent such as toluene at a temperature of about 115° C., as depicted in c.

(28) ##STR00005##

(29) Compounds of Formula 3.1, wherein R.sub.3 and R.sub.12 are as originally defined and may or may not be equivalent, can be prepared according to the method outlined in Scheme 3, step a. Compounds of Formula 3.1, wherein R.sub.3 and R.sub.12 are as originally defined and may or may not be equivalent, can be prepared from compounds of Formula 3.0, wherein R.sub.3 and R.sub.12 are as previously defined and may or may not be equivalent, by treating with a base, such as NaH and an alkyl halide, such as MeI, in a polar aprotic solvent like N,N-dimethylformamide (DMF) at a temperature of about 0′° C. to 23° C., as depicted in a.

(30) ##STR00006##

(31) Compounds of Formula 4.1, wherein R.sub.3 and R.sub.12 are as originally defined and may or may not be equivalent, can be prepared according to the method outlined in Scheme 4, step a. Compounds of Formula 4.1, wherein R.sub.3 and R.sub.12 are as originally defined and may or may not be equivalent, can be prepared from compounds of Formula 4.0, wherein R.sub.3 and R.sub.12 are as previously defined and may or may not be equivalent, by treating with a fluorination reagent, such as (diethylamino)sulfur trifluoride (DAST), in a halogenated solvent such as DCM at a temperature of about 0′° C. to 23° C., as depicted in a.

(32) ##STR00007##

(33) Compounds of Formula 5.3, wherein R.sub.3, R.sub.4, and R.sub.12 are as originally defined and R.sub.3 may or may not be equivalent to R.sub.12, can be prepared according to the methods outlined in Scheme 5, steps a-c. Compounds of Formula 5.3, wherein R.sub.3, R.sub.4, and R.sub.12 are as originally defined and R.sub.3 may or may not be equivalent to R.sub.12, can be prepared from compounds of Formula 5.0, wherein R.sub.3, R.sub.4, and R.sub.12 are as originally defined and R.sub.3 may or may not be equivalent to R.sub.12, by treating with a catalyst such as palladium on carbon (Pd/C) in a mixture of an unsaturated hydrocarbon solvent, such as cyclohexene, and a polar protic solvent, such as ethanol (EtOH), at an elevated temperature of about 65° C., as shown in a. Alternatively, compounds of Formula 5.3, wherein R.sub.3 and R.sub.12 are an electron-deficient aryl or heteroaryl group and may or may not be equivalent and R.sub.4 is hydroxyl (OH) or alkoxy, can be obtained by treating compounds of Formula 5.1, wherein R.sub.3, R.sub.4, and R.sub.12 are as previously defined and R.sub.3 may or may not be equivalent to R.sub.12, with a mixture of a hydride reagent, such as Et.sub.3SiH, and an acid, such as TFA in a halogenated solvent such as DCM at a temperature of about 0° C. to 23° C., as indicated in b. Additionally, compounds of Formula 5.3, wherein R.sub.3 and R.sub.12 are as originally defined but not an electron-deficient aryl or heteroaryl group and may or may not be equivalent, and R.sub.4 is a proton (H), can be obtained by treating the compounds of Formula 5.2, wherein R.sub.3, R.sub.4, and R.sub.12 are as previously defined and R.sub.3 may or may not be equivalent to R.sub.12, with a mixture of a hydride reagent, such as Et.sub.3SiH, and an acid, such as TFA in a halogenated solvent such as DCM at a temperature of about 0° C. to 23° C., as depicted in c.

(34) ##STR00008##

(35) Compounds of Formula 6.2, wherein R.sub.3 and R.sub.12 are an electron-deficient aryl or heteroaryl group and equivalent, can be prepared according to the methods outlined in Scheme 6, steps a-b. Compounds of Formula 6.1, wherein R.sub.3 and R.sub.12 are as described previously, can be prepared from compound of Formula 6.0, by treating with an aryl bromide, such as 4-bromobenzonitrile, in the presence of a Pd catalyst, such as XPhos Pd G3 (CAS #1445085-55-1, commercially available from Sigma-Aldrich), in a polar aprotic solvent such as THF at a temperature of about 55° C., as indicated in a. Compounds of Formula 6.2, wherein R.sub.3 and R.sub.12 are as described previously, can be prepared from compound of Formula 6.1, wherein R.sub.3 and R.sub.12 are as described previously, by treating with a hydride reagent, such as borane dimethyl sulfide complex, in the presence of a catalyst, such as (R)-(+)-2-Methyl-CBS-oxazaborolidine, in a polar protic solvent, such as methanol (MeOH), at a temperature of about 0° C., as indicated in b.

(36) ##STR00009##

(37) Compounds of Formula 7.2, wherein R.sub.3 and R.sub.12 are as originally defined and equivalent, can be prepared according to the methods outlined in Scheme 7, steps a-b. Compounds of Formula 7.1, wherein R.sub.3 and R.sub.12 are as described previously, can be prepared from compounds of Formula 7.0, by treating with a catalyst, such as SbCl.sub.5, in a halogenated solvent such as DCM at a temperature of about 23° C., as indicated in a. Compounds of Formula 7.2, wherein R.sub.3 and R.sub.12 are as described previously, can be prepared from compound of Formula 7.1, wherein R.sub.3 and R.sub.12 are as described previously, by treating with a hydride reagent, such as borane dimethyl sulfide complex, in the presence of a catalyst, such as (R)-(+)-2-Methyl-CBS-oxazaborolidine, in a polar protic solvent, such as methanol (MeOH), at a temperature of about 23° C., as indicated in b.

(38) ##STR00010##

(39) Compounds of Formula 8.1, wherein n is either 0 or 1, and W is either CH.sub.2 or O, can be prepared according to the method outlined in Scheme 8, step a. Compounds of Formula 8.1, wherein n is either 0 or 1, and W is either CH.sub.2 or 0, can be prepared from compounds of Formula 8.0, wherein n is either 0 or 1, and W is either CH.sub.2 or O, by treating with a base, such as n-butyllithium (n-BuLi), and an aldehyde, such as acetaldehyde, in a polar aprotic solvent such as THF at a temperature of about −78° C. to 23° C., as indicated in a.

(40) ##STR00011##

(41) Compounds of Formula 9.1, wherein R.sub.3 and R.sub.12 are as originally defined, can be prepared according to the method outlined in Scheme 9, step a. Compounds of Formula 9.1, wherein R.sub.3 and R.sub.12 are as originally defined, can be prepared from compounds of Formula 9.0, wherein R.sub.3 is as originally defined (Formula 9.0 is either commerically available, or could be prepared from asymmetric Shi epoxidation of the corresponding E-olefin precursor, as reported in Wang, Z. -X.; Tu, Y.; Frohn, M.; Zhang, J. -R.; Shi, Y. J. Am. Chem. Soc. 1997, 119, 11224), by treating with a pre-mixed suspension of a copper(I) salt, such as copper iodide (CuI), and an organometallic nucleophile, such as 4-(trifluoromethyl)phenylmagnesium bromide in a polar aprotic solvent such as THF, at a temperature of about −78° C. to 23° C., as shown in a.

(42) ##STR00012##

(43) Compounds of Formula 10.2, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.12 are as originally defined, can be prepared according to the method outlined in Scheme 10, step a. Compounds of Formula 10.0, wherein R.sub.1 is as originally defined, can be treated with alcohols of Formula 10.1, wherein R.sub.2, R.sub.3, R.sub.4 and R.sub.12 are as originally defined, and a coupling reagent such as 3-(ethyliminomethyleneamino)-N,N-dimethylpropan-1-amine hydrochloride (EDC), and a catalyst such as N,N-dimethylpyridin-4-amine (DMAP) in a halogenated solvent like DCM to afford compounds of Formula 10.2, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.12 are as previously defined, as shown in a.

(44) ##STR00013##

(45) Compounds of Formula 11.2, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.6, R.sub.12 and Z are as originally defined, can be prepared according to the methods outlined in Scheme 11, steps a-b. As depicted in a, compounds of Formula 11.2, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.12 are as originally defined, can be subjected to an acid, such as a 4 normal (N) solution of hydrogen chloride (HCl) in dioxane, in a halogenated solvent such as DCM to afford compounds of Formula 9.0, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.12 are as originally defined, as shown in a.

(46) Compounds of Formula 11.0, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.12 are as originally defined, can be treated with compounds of Formula 11.1, wherein R.sub.6 and Z are as originally defined, in the presence of a base, such as diisopropylethylamine (DIPEA), and a peptide coupling reagent, such as benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP), in an halogenated solvent like DCM, to afford compounds of Formula 11.2, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.6, R.sub.12 and Z are as originally defined, as shown in b.

(47) ##STR00014##

(48) Compounds of Formula 12.0, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.6, R.sub.7, R.sub.12 and Z are as originally defined, can be prepared according to the method outlined in Scheme 12, step a. As shown in a, compounds of Formula 11.2, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.6, R.sub.12 and Z are as originally defined, can be treated with an appropriate alkyl halide with or without a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as sodium carbonate (Na.sub.2CO.sub.3) or potassium carbonate (K.sub.2CO.sub.3), in a solvent like acetone at a temperature of about 55° C., or by treatment with an acyl halide in the presence of an amine base, such as pyridine, triethylamine (Et.sub.3N), DMAP, or mixtures thereof, in an aprotic solvent such as DCM, at a temperature of about 23° C., to afford compounds of Formula 12.0 wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.6, R.sub.7, R.sub.12 and Z are as originally defined.

(49) ##STR00015##

EXAMPLES

(50) The chemistry in the following examples may be conducted using either enantiomer of 2-((tert-butoxycarbonyl)amino)propanoic acid (Boc-Ala-OH) or either protected (PMB or Bn) or unprotected enantiomer of ethyl lactate.

Example 1: Preparation of (S)-2-(benzyloxy)-1,1-bis(4-fluorophenyl)propan-1-ol

(51) ##STR00016##

(52) To a solution of (S)-ethyl 2-(benzyloxy)propanoate (2.08 grams (g), 10.0 millimoles (mmol)) in tetrahydrofuran (THF; 20 milliliters (mL)) at 0° C. was slowly added (4-fluorophenyl)magnesium bromide (31.3 mL, 25.0 mmol, 0.8 molar (MI) in THF) over a 10 minute (min) period. The reaction vessel was allowed to warm slowly to room temperature over 2 hours (h), and the reaction mixture was quenched by careful addition of saturated (sat.) aqueous (aq.) ammonium chloride (NH.sub.4Cl; 50 mL). The mixture was diluted with diethyl ether (Et.sub.2O; 50 mL), the phases were separated, and the aq. phase was extracted with Et.sub.2O (2×50 mL). The combined organic phases were washed with sat. aq. sodium chloride (NaCl, brine; 100 mL), dried over sodium sulfate (Na.sub.2SO.sub.4), filtered, and concentrated. The resulting oil was purified by flash column chromatography (silica gel (SiO.sub.2), 0.fwdarw.5% acetone in hexanes) to afford the title compound (3.28 g, 93%) as a colorless oil: .sup.1H NMR (300 MHz, CDCl.sub.3) δ 7.47-7.38 (m, 2H), 7.38-7.27 (m, 5H), 7.17-7.09 (m, 2H), 7.04-6.89 (m, 4H), 4.64 (dd, J=11.4, 0.7 Hz, 1H), 4.51-4.38 (m, 2H), 3.12 (s, 1H), 1.11 (d, J=6.1 Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3) δ −116.19, −116.41; ESIMS m/z 377 ([M+Na].sup.+).

Example 2A: Preparation of (S)-4,4′-(2-(benzyloxy)propane-1,1-diyl)bis(fluorobenzene)

(53) ##STR00017##

(54) To a solution of (S)-2-(benzyloxy)-1,1-bis(4-fluorophenyl)propan-1-ol (709 milligrams (mg), 2.00 mmol) in dichloromethane (DCM; 20 mL) at 0° C. was added triethylsilane (Et.sub.3SiH; 3.19 mL, 20.0 mmol) followed by 2,2,2-trifluoroacetic acid (TFA; 1.53 mL, 20.0 mmol). The mixture was stirred at 0° C. for 1 h. The resulting solution was quenched by careful addition of sat. aq. sodium bicarbonate (NaHCO.sub.3; 20 mL). The phases were separated, and the aq. phase was extracted with DCM (2×30 mL). The combined organic phases were washed with brine (50 mL), dried over Na.sub.2SO.sub.4, filtered, and concentrated. The resulting oil was purified by flash column chromatography (SiO.sub.2, 0.fwdarw.10% acetone in hexanes) to afford the title compound (627 mg, 92%) as a white solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.31-7.22 (m, 5H), 7.21-7.16 (m, 2H), 7.10-7.03 (m, 2H), 7.00-6.91 (m, 4H), 4.54 (dd, J=11.5, 0.7 Hz, 1H), 4.31 (dd, J=11.6, 0.8 Hz, 1H), 4.14 (dq, J=8.1, 6.1 Hz, 1H), 3.93 (d, J=8.1 Hz, 1H), 1.18 (d, J=6.0 Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3) δ −116.60, −117.10; ESIMS (m/z) 361 ([M+Na].sup.+).

Example 2B: Preparation of (S)-(2-(benzyloxy)-1-methoxypropane-1,1-diyl)dibenzene

(55) ##STR00018##

(56) To a suspension of sodium hydride (NaH: 52.0 mg, 1.30 mmol, 60% weight per weight (w/w) in mineral oil) in N,N-dimethylformamide (DMF; 3 mL) at 0° C. was added a solution of (S)-2-(benzyloxy)-1,1-diphenylpropan-1-ol (318 mg, 1 mmol) in DMF (1 mL). The reaction mixture was stirred at room temperature for 30 min and then cooled to 0° C. Iodomethane (Mel; 93.0 microliters (μL), 1.50 mmol) was added, and the reaction mixture was stirred at room temperature for 1 h. The resulting solution was quenched by careful addition of sat. aq. NaHCO.sub.3 (10 mL). The mixture was diluted with diethyl ether (Et.sub.2O; 10 mL), the phases were separated, and the aq. phase was extracted with Et.sub.2O (2×10 mL). The combined organic phases were washed with brine (20 mL), dried over Na.sub.2SO.sub.4, filtered, and concentrated. The resulting oil was purified by flash column chromatography (SiO.sub.2, 0.fwdarw.5% acetone in hexanes) to afford the title compound (295 mg, 89%) as a colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.47-7.41 (m, 2H), 7.40-7.35 (m, 2H), 7.33-7.18 (m, 11H), 4.69 (d, J=11.9 Hz, 1H), 4.54 (d, J=12.3 Hz, 1H), 4.50 (q, J=6.1 Hz, 1H), 3.13 (s, 3H), 1.10 (d, J=6.1 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 142.96, 141.31, 138.79, 129.13, 128.54, 128.14, 127.61, 127.16, 127.08, 126.95, 126.69, 99.99, 85.35, 78.13, 70.80, 52.46, 13.65; ESIMS (m/z) 333 ([M+H].sup.+).

Example 2C: Preparation of (S)-(2-(benzyloxy)-1-fluoropropane-1,1-diyl)dibenzene

(57) ##STR00019##

(58) To a solution of (S)-2-(benzyloxy)-1,1-diphenylpropan-1-ol (300 mg, 0.942 mmol) in DCM (5 mL) at 0° C. was added (diethylamino)sulfur trifluoride (DAST; 1.88 mL, 1.88 mmol, 1 M in DCM). The reaction was slowly warmed to room temperature over 3 h. The resulting solution was quenched by careful addition of sat. aq. NaHCO.sub.3 (5 mL). The phases were separated, and the aq. phase was extracted with DCM (2×10 mL). The combined organic phases were washed with brine (10 mL), dried over Na.sub.2SO.sub.4, filtered, and concentrated. The resulting oil was purified by flash column chromatography (SiO.sub.2, 0.fwdarw.10/a acetone in hexanes) to afford the title compound (300 mg, 98%) as a colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.58-7.49 (m, 2H), 7.43-7.37 (m, 2H), 7.36-7.20 (m, 9H), 7.09-6.99 (m, 2H), 4.47 (d, J=11.7 Hz, 1H), 4.37-4.25 (m, 2H), 1.26 (dd, J=6.3, 1.3 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 142.23 (d, J=22.7 Hz), 141.00 (d, J=23.5 Hz), 138.03, 128.21, 128.16, 127.90 (d, J=1.5 Hz), 127.80, 127.72 (d, J=1.7 Hz), 127.52, 127.42 (d, J=1.3 Hz), 126.23 (d, J=9.6 Hz), 125.93 (d, J=8.7 Hz), 99.96 (d, J=180.8 Hz), 78.91 (d, J=26.9 Hz), 71.68, 14.47 (d, J=3.6 Hz); .sup.19F NMR (376 MHz, CDCl.sub.3) δ −159.80.

Example 2D, Step 1: Preparation of (S)—O-(2-(benzyloxy)-1,1-bis(3,4,5-trifluorophenyl)propyl)S-methyl Carbonodithioate

(59) ##STR00020##

(60) To a solution of (S)-2-(benzyloxy)-1,1-bis(3,4,5-trifluorophenyl)propan-1-ol (496 mg, 1.16 mmol) in anhydrous THF (5.8 mL) was added NaH (93.0 mg, 2.33 mmol), followed by imidazole (3.96 mg, 0.0580 mmol), and the reaction mixture was stirred at ambient temperature for 1 h. Carbon disulfide (562 μL, 9.30 mmol) was added via syringe in one portion, followed by MeI (579 μL, 9.30 mmol), and the reaction mixture was stirred at ambient temperature for 2 h. The reaction mixture was diluted with Et.sub.2O (5 mL) and quenched with sat. aq. NH.sub.4Cl (10 mL). The layers were separated, and the aq. layer was extracted with Et.sub.2O (3×10 mL). The combined organic layers were dried over magnesium sulfate (MgSO.sub.4), filtered and concentrated to afford an orange/brown oil. The crude oil was purified by flash column chromatography (SiO.sub.2, 0.fwdarw.50% ethyl acetate (EtOAc) in hexanes) to afford the title compound (627 mg, 94%) as a clear, bright yellow colored oil: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.40-7.27 (m, 3H), 7.24-7.16 (m, 2H), 7.02 (dd, J=9.1, 6.6 Hz, 2H), 6.96 (dd, J=8.8, 6.5 Hz, 2H), 5.44 (q, J=6.1 Hz, 1H), 4.66 (d, J=11.6 Hz, 1H), 4.51 (d, J=11.6 Hz, 1H), 2.49 (s, 3H), 1.16 (d, J=6.1 Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3) δ −133.89 (d, J=20.7 Hz), −134.73 (d, J=20.6 Hz), −159.83 (t, J=20.6 Hz), −160.56 (t, J=20.7 Hz); (Thin film) 2922, 1721, 1622, 1595, 1526, 1436, 1344, 1241, 1217, 1197, 1119, 1088, 1040, 965, 908, 861, 822, 730, 712, 697, 672 cm.sup.−1.

Example 2D, Step 2: Preparation of (S)-5,5′-(2-(benzyloxy)propane-1,1-diyl)bis(1,2,3-trifluorobenzene)

(61) ##STR00021##

(62) A solution of (S)—O-(2-(benzyloxy)-1,1-bis(3,4,5-trifluorophenyl)propyl)S-methyl carbonodithioate (598 mg, 1.16 mmol) in toluene (200 mL) was degassed by a freeze-pump-thaw procedure (3 cycles using liquid nitrogen (N.sub.2)) under an atmosphere of N.sub.2. Tributyltin hydride (3.12 mL, 11.6 mmol) was then added, the reaction flask was fitted with a reflux condenser, and the reaction mixture was heated to a light reflux (115° C.). A solution of azobisisobutyronitrile (AIBN; 0.200 g, 1.22 mmol) in degassed toluene (3 cycles via liquid N.sub.2; 32 mL) was added via syringe down the reflux condenser over 3 h. Once slow addition of the AIBN was complete, the reaction mixture was stirred at reflux overnight. The solvent was removed in vacuo to provide a pale yellow oil. The crude oil was purified by flash column chromatography (SiO.sub.2, 0430% EtOAc in hexanes) to afford the title compound (358 mg, 72%) as a clear, colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.28 (d, J=6.6 Hz, 3H), 7.17-7.06 (m, 2H), 6.92 (dd, J=8.5, 6.5 Hz, 2H), 6.79 (dd, J=8.3, 6.4 Hz, 2H), 4.59 (d, J=11.7 Hz, 1H), 4.31 (d, J=11.7 Hz, 1H), 4.02 (p, J=6.2 Hz, 1H), 3.76 (d, J=6.8 Hz, 1H), 1.19 (d, J=6.1 Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3) δ −133.80 (d, J=20.5 Hz), −134.34 (d, J=20.5 Hz), −162.54 (t, J=20.5 Hz), −162.84 (t, J=20.5 Hz); (Thin film) 2871, 1621, 1526, 1445, 1345, 1262, 1235, 1116, 1096, 1043, 859, 802, 728, 698, 679 cm.sup.−1.

Example 3A: Preparation of (S)-1,1-bis(4-fluorophenyl)propan-2-ol

(63) ##STR00022##

(64) To a solution of (S)-4,4′-(2-(benzyloxy)propane-1,1-diyl)bis(fluorobenzene) (575 mg, 1.70 mmol) in ethanol (EtOH; 11 mL) and cyclohexene (5.5 mL) at room temperature was added palladium on carbon (Pd/C; 362 mg, 0.0850 mmol, 2.5% w/w of Pd). The reaction mixture was stirred at 65° C. for 2 h, cooled to room temperature, filtered through a plug of Celite®, and concentrated to afford the title compound (415 mg, 98%) as a colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.36-7.29 (m, 2H), 7.25-7.18 (m, 2H), 7.09-6.93 (m, 4H), 4.47 (dqd, J=8.2, 6.1, 3.3 Hz, 1H), 3.80 (d, J=8.3 Hz, 1H), 1.55 (d, J=3.3 Hz, 1H), 1.19 (d, J=6.1 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.6) δ 162.90 (d, J=23.3 Hz), 160.46 (d, J=23.1 Hz), 138.15 (d, J=3.1 Hz), 136.94 (d, J=3.6 Hz), 130.14 (d, J=7.8 Hz), 129.55 (d, J=7.8 Hz), 115.70 (d, J=18.8 Hz), 115.49 (d, J=18.8 Hz), 70.07, 58.61, 21.63; .sup.19F NMR (376 MHz, CDCl.sub.3) δ −115.84, −116.19.

Example 3B: Preparation of (S)-1,1-bis(2-fluorophenyl)propane-1,2-diol

(65) ##STR00023##

(66) To a solution of (S)-1,1-bis(2-fluorophenyl)-2-((4-methoxybenzyl)oxy)propan-1-ol (790 mg, 2.06 mmol) in DCM (20 mL) at 0° C. was added Et.sub.3SiH (3.28 mL, 20.6 mmol) followed by TFA (1.57 mL, 20.6 mmol). The mixture was stirred at 0° C. for 1 h. The resulting solution was quenched by careful addition of sat. aq. NaHCO.sub.3 (20 mL). The phases were separated, and the aq. phase was extracted with DCM (2×30 mL). The combined organic phases were washed with brine (50 mL), dried over Na.sub.2SO.sub.4, filtered, and concentrated. The resulting oil was purified by flash column chromatography (SiO.sub.2, 0.fwdarw.10% acetone in hexanes) to afford the title compound (388 mg, 71%) as a colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) S 7.90-7.77 (m, 1H), 7.70 (tt, J=8.2, 1.5 Hz, 1H), 7.31-7.10 (m, 4H), 6.97 (ddd, J=12.7, 8.1, 1.3 Hz, 1H), 6.88 (ddd, J=11.8, 8.0, 1.4 Hz, 1H), 5.11 (qd, J=6.3, 2.3 Hz, 1H), 3.49 (s, 1H), 2.27 (s, 1H), 1.09 (d, J=6.3 Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3) δ −112.90 (d, J=8.3 Hz), −113.92 (d, J=8.4 Hz); ESIMS (m/z) 551 ([2M+Na].sup.+).

Example 3C: Preparation of (S)-1,1-bis(4-bromophenyl)propan-2-ol

(67) ##STR00024##

(68) To a solution of (S)-1,1-bis(4-bromophenyl)-2-((4-methoxybenzyl)oxy)propan-1-ol (1.80 g, 3.56 mmol) in DCM (18 mL) at 0° C. was added Et.sub.3SiH (5.68 mL, 35.6 mmol) followed by TFA (2.72 mL, 35.6 mmol). The mixture was warmed slowly to room temperature over 3 h. The resulting solution was quenched by careful addition of sat. aq. NaHCO.sub.3 (20 mL). The phases were separated, and the aq. phase was extracted with DCM (2×30 mL). The combined organic phases were washed with brine (50 mL), dried over Na.sub.2SO.sub.4, filtered, and concentrated. The resulting oil was purified by flash column chromatography (SiO.sub.2, 0410% acetone in hexanes) to afford the title compound (742 mg, 56%) as a colorless oil: .sup.1H NMR (300 MHz, CDCl.sub.3) δ 7.51-7.36 (m, 4H), 7.25-7.17 (m, 2H), 7.18-7.06 (m, 2H), 4.48 (dq, J=8.2, 6.1 Hz, 1H), 3.76 (d, J=8.2 Hz, 1H), 2.80 (s, 1H), 1.19 (d, J=6.2 Hz, 3H); .sup.13C NMR (75 MHz, CDCl.sub.3) δ 140.94, 139.85, 131.98, 131.85, 130.39, 129.84, 121.06, 120.72, 69.82, 58.91, 21.65; (Thin film) 3390, 3024, 2969, 2900, 1486, 1072 cm.sup.−1.

Example 3D, Step 1: Preparation of (S)-1,1-bis(4-((trimethylsilyl)ethynyl)-phenyl)propan-2-ol

(69) ##STR00025##

(70) To a solution of (S)-1,1-bis(4-bromophenyl)propan-2-ol (1.01 g, 2.72 mmol) in THF (9 mL) was added bis(triphenylphosphine)palladium dichloride (0.095 g, 0.136 mmol) and copper(I) iodide (CuI; 0.026 g, 0.136 mmol). The mixture was sparged with N.sub.2 for 20 min, and triethylamine (Et.sub.3N; 4.53 mL) was added dropwise. To the resulting mixture was added ethynyltrimethylsilane (1.15 mL, 8.15 mmol) dropwise, and the mixture was heated to reflux and stirred overnight. The mixture was cooled to room temperature, and the reaction was quenched with sat. aq. NaHCO.sub.3. The products were extracted with EtOAc (2×), and the combined organic layers were washed with brine, dried over Na.sub.2SO.sub.4, filtered and concentrated. The crude residue was then purified by flash column chromatography (SiO.sub.2, 0.fwdarw.20% acetone in hexanes) to provide the title compound (495 mg, 45%) as a brown foam: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.48-7.42 (m, 2H), 7.42-7.37 (m, 2H), 7.33-7.27 (m, 2H), 7.24-7.17 (m, 2H), 4.51 (dqd, J=12.2, 6.1, 3.5 Hz, 1H), 3.81 (d, J=8.3 Hz, 1H), 1.60 (d, J=3.8 Hz, 1H), 1.18 (d, J=6.1 Hz, 3H), 0.26 (s, 9H), 0.26 (s, 9H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 142.55, 141.48, 132.42, 132.29, 128.69, 128.15, 121.90, 121.57, 104.76, 104.71, 94.49, 94.33, 69.76, 59.96, 21.55, 0.00; (Thin film) 3397, 2960, 2156, 1501, 1248, 861, 840 cm.sup.−1, HRMS-ESI (m/z) [M+H].sup.+ calcd for C.sub.25H.sub.33OSi.sub.2, 405.2064; found, 405.2070.

Example 3D, Step 2: Preparation of (S)-1,1-bis(4-ethynylphenyl)propan-2-ol

(71) ##STR00026##

(72) To a solution of (S)-1,1-bis(4-((trimethylsilyl)ethynyl)phenyl)propan-2-ol (0.470 g, 1.16 mmol) in methanol (MeOH; 5.8 mL) was added potassium carbonate (K.sub.2CO.sub.3; 0.482 g, 3.48 mmol). The mixture was stirred for 1 h at room temperature and then filtered through Celite®. The filter cake was washed with MeOH, and the filtrate was concentrated. The crude material was purified by flash column chromatography (SiO.sub.2, 0.fwdarw.20% acetone in hexanes) to provide the title compound (288 mg, 95%) as a yellow oil: .sup.1H NMR (300 MHz, CDCl.sub.3) δ 7.48-7.43 (m, 2H), 7.43-7.39 (m, 2H), 7.35-7.29 (m, 2H), 7.24-7.19 (m, 2H), 4.51 (dqd, J=8.3, 6.1, 3.7 Hz, 1H), 3.82 (d, J=8.3 Hz, 1H), 3.05 (s, 1H), 3.04 (s, 1H), 1.63-1.55 (m, 1H), 1.18 (d, J=6.1 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 142.84, 141.82, 132.60, 132.48, 128.74, 128.22, 120.87, 120.57, 83.31, 83.29, 77.39, 77.29, 69.73, 59.96, 21.66; (Thin film) 3436, 3280, 2968, 2106, 1499, 1075, 825 cm.sup.−1; HRMS-ESI (m z) [M+H].sup.+ calcd for C.sub.19H.sub.17O, 261.1274; found, 261.1272.

Example 3D, Step 3: Preparation of (S)-1,1-bis(4-ethylphenyl)propan-2-ol

(73) ##STR00027##

(74) To a solution of (S)-1,1-bis(4-ethynylphenyl)propan-2-ol (0.144 g, 0.553 mmol) in EtOAc (2.8 mL) was added palladium (5% weight (wt) on carbon, dry basis; 0.235 g, 0.055 mmol). The mixture was stirred under a balloon of hydrogen overnight. The mixture was filtered through Celite®, and the filter cake was washed with EtOAc. The combined filtrate was then concentrated, and the crude residue was purified by flash column chromatography (SiO.sub.2, 0.fwdarw.25% acetone in hexanes) to provide the title compound (97.0 mg, 65%) as a clear oil. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.33-7.25 (m, 2H), 7.22-7.15 (m, 2H), 7.18-7.11 (m, 2H), 7.10 (d, J=8.1 Hz, 2H), 4.51 (dqd, J=8.7, 6.1, 2.5 Hz, 1H), 3.74 (d, J=8.9 Hz, 1H), 2.65-2.53 (m, 4H), 1.68 (d, J=2.8 Hz, 1H), 1.23-1.14 (m, 9H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 142.74, 142.33, 139.94, 138.91, 128.48, 128.40, 128.07, 128.02, 70.19, 60.02, 28.41, 28.39, 21.37, 15.47, 15.46; (Thin film) 3421, 2963, 1510, 1110, 821 cm.sup.−1; HRMS-ESI (m/z) ([M+Na].sup.+) calcd for C.sub.19H.sub.24NaO, 291.1719; found, 291.1725.

Example 3E: Preparation of 1-(9H-xanthen-9-yl)ethanol

(75) ##STR00028##

(76) To a solution of 9H-xanthene (364 mg, 2.00 mmol) in THF (10 mL) at −78° C. was added n-butyllithium (2.5 M in hexanes; 0.880 mL, 2.20 mmol). The mixture was stirred at −78° C. for 30 min. Acetaldehyde (0.226 mL, 4.00 mmol) was added, and the reaction mixture was warmed slowly to room temperature overnight. The resulting solution was quenched by careful addition of sat. aq. NH.sub.4Cl (10 mL). The phases were separated, and the aq. phase was extracted with Et.sub.2O (2×15 mL). The combined organic phases were washed with brine (20 mL), dried over Na.sub.2SO.sub.4, filtered, and concentrated. The resulting oil was purified by flash column chromatography (SiO.sub.2, 0.fwdarw.10% acetone in hexanes) to afford the title compound (216 mg, 48%) as a colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.33-7.22 (m, 4H), 7.17-7.04 (m, 4H), 3.99 (d, J=5.1 Hz, 1H), 3.96-3.82 (m, 1H), 1.54 (d, J=6.0 Hz, 1H), 1.00 (d, J=6.3 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 152.94, 152.65, 129.54, 129.30, 128.19, 128.17, 123.18, 123.14, 122.48, 121.73, 116.59, 116.41, 73.07, 47.06, 18.81; ESIMS (m/z) 475 ([2M+Na].sup.+).

Example 3F: Preparation of (1S,2S)-1-phenyl-1-(4-(trifluoromethyl)phenyl)propan-2-ol

(77) ##STR00029##

(78) To a mixture of magnesium turnings (102 mg, 4.20 mmol) in Et.sub.2O (4 mL) was added 1-bromo-4-(trifluoromethyl)benzene (0.588 mL, 4.20 mmol) at room temperature, followed by MeI (5 μL). Upon warming to a gentle boil using a heat gun, the mixture turned a yellow/brown color. The reaction was then stirred in a water bath at room temperature for 30 min until almost all the magnesium was consumed. This was added to a suspension of copper(I) iodide (CuI; 400 mg, 2.10 mmol) in Et.sub.2O (4 mL) at −78° C. The reaction was stirred at −20° C. for 30 min, then cooled to −78° C., and (2S,3S)-2-methyl-3-phenyloxirane (0.201 mL, 1.50 mmol) was added. The resulting mixture was warmed slowly to room temperature overnight. The resulting solution was quenched by careful addition of sat. aq. NH.sub.4Cl (10 mL). The phases were separated, and the aq. phase was extracted with Et.sub.2O (2×15 mL). The combined organic phases were washed with brine (20 mL), dried over Na.sub.2SO.sub.4, filtered, and concentrated. The resulting oil was purified by flash column chromatography (SiO.sub.2, 0-10% acetone in hexanes) to afford the title compound (390 mg, 94%) as a light yellow oil: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.60-7.50 (m, 2H), 7.48-7.38 (m, 2H), 7.38-7.33 (m, 4H), 7.30-7.23 (m, 1H), 4.58 (dqd, J=8.4, 6.1, 3.5 Hz, 1H), 3.88 (d, J=8.5 Hz, 1H), 1.65 (d, J=3.6 Hz, 1H), 1.20 (d, J=6.1 Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3) δ −62.49; ESIMS (m/z) 263 ([M-OH].sup.+).

Example 3G, Step 1: Preparation of 4,4′-(2-oxopropane-1,1-diyl)dibenzonitrile

(79) ##STR00030##

(80) To a suspension of 4-bromobenzonitrile (546 mg, 3.00 mmol) and cesium carbonate (977 mg, 3.00 mmol) in THF (10 mL) under an N.sub.2 atmosphere was added acetone (1.10 mL, 15.00 mmol), followed by X-Phos Pd G3 (50.8 mg, 0.060 mmol). Then, the vial was sealed and heated to 55° C. for 4 days. The reaction was diluted with EtOAc (30 mL) and washed with sat. NH.sub.4Cl (3×10 mL), water (15 mL), and brine (15 mL). Then the organic phase was dried over Na.sub.2SO.sub.4, filtered, and concentrated. The resulting oil was purified by flash column chromatography (SiO.sub.2, 0.fwdarw.40% EtOAc in hexanes) to afford the title compound (174 mg, 22%) as a colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.66 (d, J=8.4 Hz, 4H), 7.34 (d, J=8.3 Hz, 4H), 5.21 (s, 1H), 2.29 (s, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 203.68, 142.15, 132.75, 129.64, 118.21, 112.00, 64.25, 30.43; ESIMS m/z 261 ([M+H].sup.+).

Example 3G, Step 2: Preparation of (S)-4,4′-(2-hydroxypropane-1,1-diyl)dibenzonitrile

(81) ##STR00031##

(82) To a solution of 4,4′-(2-oxopropane-1,1-diyl)dibenzonitrile (174 mg, 0.668 mmol) in toluene (4.5 mL) was added (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (1 M solution in toluene, 66.8 μL, 0.067 mmol). Then, the reaction was cooled to 0° C. and a solution of BH.sub.3-DMS (69.8 μl, 0.735 mmol) in 0.5 mL toluene was added over 2 min. The flask was left to stir at 0° C. After 2 h, the reaction was quenched with methanol (0.5 mL), diluted with EtOAc and added water. Phases were separated and the aqueous phase was extracted with EtOAc×2. The combined organic phases were washed with brine (20 mL), dried over Na.sub.2SO.sub.4, filtered, and concentrated. The resulting oil was purified by flash column chromatography (SiO.sub.2, 0.fwdarw.50% EtOAc in hexanes) to afford the title compound (99.7 mg, 57%) as a colorless oil. .sup.1H NMR (400 MHz, CDCl.sub.3) δ d 7.60 (dd, J=8.4, 6.8 Hz, 4H), 7.51-7.46 (m, 2H), 7.43-7.37 (m, 2H), 4.63-4.47 (m, 1H), 3.97 (d, J=7.5 Hz, 1H), 1.97 (d, J=3.8 Hz, 1H), 1.21 (d, J=6.2 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 146.91, 145.86, 132.60, 132.45, 129.90, 129.19, 118.58, 118.51, 110.96, 110.92, 69.19, 59.56, 22.27; ESIMS m/z 263 ([M+H]).

Example 3H, Step 1: Preparation of 3,3-diphenylbutan-2-one

(83) ##STR00032##

(84) To a magnetically stirred mixture of 2,3-diphenylbutane-2,3-diol (500 mg, 2.06 mmol) in DCM (10 mL) was added antimony pentachloride (26.5 μL, 0.206 mmol) under air atmosphere. The reaction mixture was stirred at 25° C. for 1 h and then was quenched by slow addition of sat. aq. NaHCO.sub.3. The resulting mixture was diluted with water and additional DCM, and the organic layer was separated by passing through a phase separator. The resulting oil was purified by flash column chromatography (SiO.sub.2, 045% acetone in hexanes) to afford the title compound (330 mg, 71%) as a colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.36-7.31 (m, 4H), 7.30-7.25 (m, 2H), 7.23-7.15 (m, 4H), 2.11 (s, 3H), 1.87 (s, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 209.16, 143.59, 128.36, 126.91, 62.32, 27.62, 26.42; ESIMS m/z 225 ([M+H].sup.+).

Example 3H, Step 2: Preparation of (S)-3,3-diphenylbutan-2-ol

(85) ##STR00033##

(86) To a solution of 3,3-diphenylbutan-2-one (150 mg, 0.669 mmol) in toluene (4.5 mL) was added (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (1 M solution in toluene, 134 μL, 0.134 mmol). Then, a solution of BH.sub.3-DMS (70.2 μL, 0.702 mmol) in 0.5 mL of toluene was added to the reaction mixture over 2 min. The flask was left to stir at room temperature. After 1 h, the reaction was quenched with methanol (0.5 mL). DCM and water were added, and the phases were separated. The aqueous phase was extracted with DCM (2×). The combined organic phases were washed with brine (20 mL), dried over Na.sub.2SO.sub.4, filtered, and concentrated. The resulting oil was purified by flash column chromatography (SiO.sub.2, 0420% acetone in hexanes) to afford the title compound (150 mg, 99%) as a colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) δ d 7.39-7.17 (m, 10H), 4.70-4.61 (m, 1H), 1.67 (s, 3H), 1.51 (d, J=4.9 Hz, 1H), 1.11 (d, J=6.3 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 147.30, 145.86, 128.40, 128.15, 128.05, 127.79, 126.20, 126.01, 72.28, 51.77, 23.26, 18.39; ESIMS m/z 227 ([M+H].sup.+).

Example 3I, Step 1: Preparation of (S)-1,1-bis(2,3-dimethoxyphenyl)propane-1,2-diol

(87) ##STR00034##

(88) To a solution of isopropylmagnesium lithium chloride (1.3 M in THF, 6.1 mL, 8.00 mmol) was added THF (2 mL) and 1-bromo-2,3-dimethoxybenzene (1.74 g, 8.00 mmol). The resulting brown solution was heated to a gentle reflux (75° C. external temp) for 2.5 h, then cooled to 0° C. in an ice water bath. (S)-methyl 2-hydroxypropanoate (0.191 ml, 2 mmol) was then added dropwise via syringe. The reaction was stirred at 0° C. for 1 h, then removed from the cold bath and stirred overnight at rt. The reaction was cooled to 0° C. in an ice water bath, diluted with water (20 mL), brine (20 mL), and Et.sub.2O (40 mL), and was quenched with 1 N HCl (8 mL). The phases were separated, and the aqueous phase was extracted with Et.sub.2O (20 mL). The organic phases were combined, dried over MgSO.sub.4, filtered, and concentrated to provide an oil. Purification by automated silica gel column chromatography (5-50% EtOAc in hexanes) provided the title compound (568 mg, 82%) as a yellow, crystalline solid: .sup.1H NMR (300 MHz, CDCl.sub.3) δ 7.43 (td, J=8.0, 1.5 Hz, 2H), 7.11 (td, J=8.1, 4.9 Hz, 2H), 6.83 (dd, J=8.1, 1.4 Hz, 2H), 5.06-4.82 (m, 1H), 4.74 (d, J=1.2 Hz, 1H), 3.81 (s, 3H), 3.80 (s, 3H), 3.20 (s, 3H), 3.04 (s, 3H), 2.86 (d, J=9.5 Hz, 1H), 0.97 (d, J=6.4 Hz, 3H); .sup.13C NMR (126 MHz, CDCl.sub.3) δ 152.89, 152.82, 146.94, 145.53, 139.56, 138.92, 123.32, 123.26, 122.01, 119.01, 111.30, 79.20, 77.22, 60.07, 59.26, 55.77, 55.64, 18.34; HRMS-ESI (m/z) ([M+Na].sup.+) calcd for C.sub.19H.sub.24O.sub.6Na, 371.1465; found, 371.1456.

Example 3I, Step 2: Preparation of 1,1-bis(2,3-dimethoxyphenyl)propan-2-one

(89) ##STR00035##

(90) To a solution of (S)-1,1-bis(2,3-dimethoxyphenyl)propane-1,2-diol (560 mg, 1.61 mmol) in anhydrous CH.sub.2Cl.sub.2 (8 mL) at 0° C. was added triethylsilane (770 μl, 4.82 mmol) and trifluoroacetic acid (TFA, 124 μL, 1.61 mmol). The resulting solution was stirred at 0° C. for 2 h, then removed from the cold bath and stirred for 2 h. TFA (248 μL, 3.2 mmol) was added, and the reaction was then stirred overnight at rt. The reaction was diluted with water (25 mL) and extracted with CH.sub.2Cl.sub.2 (3×25 mL). The organic extracts were dried over Na.sub.2SO.sub.4, filtered, and concentrated to provide an oil. Purification by automated silica gel column chromatography (5-25% acetone in hexanes) provided the title compound (396 mg, 75%) as a white solid: .sup.1H NMR (300 MHz, CDCl.sub.3) δ 6.99 (t, J=8.0 Hz, 2H), 6.87 (dd, J=8.2, 1.5 Hz, 2H), 6.67-6.54 (m, 2H), 5.86 (s, 1H), 3.87 (s, 6H), 3.75 (s, 6H), 2.25 (s, 3H); .sup.13C NMR (126 MHz, CDCl.sub.3) δ 207.18, 152.69, 147.02, 132.23, 123.74, 121.61, 111.64, 60.36, 55.74, 51.96, 29.80; HRMS-ESI (m/z) ([M+Na].sup.+) calcd for C.sub.19H.sub.22O.sub.5Na, 353.1359; found, 353.1353.

Example 3I, Step 3: Preparation of 1,1-bis(2,3-dimethoxyphenyl)propan-2-ol

(91) ##STR00036##

(92) To a solution of 1,1-bis(2,3-dimethoxyphenyl)propan-2-one (356 mg, 1.08 mmol) in methanol (3.5 mL) was added sodium borohydride (61 mg, 1.6 mmol). The resulting solution was stirred at rt for 20 h, then was quenched with sat'd NH.sub.4Cl (1 mL), diluted with water (20 mL) and extracted with CH.sub.2Cl.sub.2 (3×20 mL). The organic extracts were combined, dried over Na.sub.2SO.sub.4, filtered, and concentrated to provide the title compound (360 mg, 100%) as an oil: .sup.1H NMR (300 MHz, CDCl.sub.3) δ 7.16-6.88 (m, 4H), 6.79 (ddd, J=9.6, 7.8, 1.9 Hz, 2H), 4.81 (d, J=8.3 Hz, 1H), 4.53-4.32 (m, 1H), 3.84 (s, 3H), 3.84 (s, 3H), 3.77 (s, 3H), 3.76 (s, 3H), 2.04 (d, J=4.2 Hz, 1H), 1.22 (d, J=6.2 Hz, 3H); .sup.13C NMR (126 MHz, CDCl.sub.3) δ 152.98, 152.83, 147.71, 147.04, 136.17, 135.33, 123.94, 123.62, 120.96, 120.84, 110.76, 110.48, 70.32, 60.26, 60.20, 55.66, 55.63, 45.11, 21.80; IR (neat film) 3451, 2935, 2833, 1582, 1473, 1428, 1266, 1215, 1167, 1125, 1088, 1068, 1004, 964, 908, 835, 809, 787, 748, 728.

Example 4A: Preparation of (S)—(S)-1,1-diphenylpropan-2-yl 2-((tert-butoxycarbonyl)amino)-propanoate

(93) ##STR00037##

(94) To a solution of (S)-1,1-diphenylpropan-2-ol (317 mg, 1.493 mmol) in DCM (15 mL) at 0° C. were added (S)-2-((tert-butoxycarbonyl)amino)propanoic acid (Boc-Ala-OH; 311 mg, 1.64 mmol) and N,N-dimethylpyridin-4-amine (DMAP; 18.2 mg, 0.149 mmol) followed by N.sup.1-((ethylimino)methylene)-N.sup.3,N.sup.3-dimethylpropane-1,3-diamine hydrochloride (EDC; 573 mg, 2.99 mmol), and the reaction mixture was stirred at room temperature overnight and concentrated to give a yellow oil. The crude material was purified by flash column chromatography (SiO.sub.2, 1.fwdarw.10% acetone in hexanes) to afford the title compound (433 mg, 75%) as a colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.42-7.07 (m, 10H), 5.80 (dq, J=10.1, 6.1 Hz, 1H), 4.97 (d, J=8.0 Hz, 1H), 4.19-4.06 (m, 1H), 4.03 (d, J=10.1 Hz, 1H), 1.41 (s, 9H), 1.23 (d, J=6.1 Hz, 3H), 0.76 (d, J=7.2 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 172.83, 154.96, 141.52, 141.26, 128.79, 128.50, 128.10, 128.08, 126.91, 126.67, 79.62, 73.10, 57.98, 49.21, 28.33, 19.31, 17.98; ESIMS m/z 384 ([M+H].sup.+).

Example 5, Step 1: Preparation of (S)-1-(((S)-1,1-diphenylpropan-2-yl)oxy)-1-oxopropan-2-aminium Chloride

(95) ##STR00038##

(96) To a solution of (S)—(S)-1,1-diphenylpropan-2-yl 2-((tert-butoxycarbonyl)amino)propanoate (Cmpd 2; 433 mg, 1.13 mmol) in DCM (6 mL) was added a 4 N solution of HCl in dioxane (2.8 mL, 11.3 mmol), and the mixture was stirred for 3 h at room temperature. The solvent was evaporated under a stream of N.sub.2 to provide the title compound (360 mg, 100%) as a white solid: ESIMS (m/z) 284 ([M+H].sup.+).

Example 5, Step 2: Preparation of (S)—(S)-1,1-diphenylpropan-2-yl 2-(3-hydroxy-4-methoxypicolinamido)propanoate

(97) ##STR00039##

(98) To a solution of (S)-1-(((S)-1,1-diphenylpropan-2-yl)oxy)-1-oxopropan-2-aminium chloride (Cmpd 46; 361 mg, 1.13 mmol) and 3-hydroxy-4-methoxypicolinic acid (210 mg, 1.24 mmol) in DCM (11 mL) were added benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP; 646 mg, 1.24 mmol) and N-ethyl-N-isopropylpropan-2-amine (DIPEA; 0.651 mL, 3.72 mmol), and the reaction mixture was stirred for 2 h at room temperature. The solvent was evaporated and the crude oil was purified by flash column chromatography (SiO.sub.2, 1-50% acetone in hexanes) to afford the title compound (340 mg, 70%) as a white foam: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 12.10 (s, 1H), 8.34 (d, J=8.0 Hz, 1H), 7.98 (d, J=5.2 Hz, 1H), 7.38-7.06 (m, 101-), 6.86 (d, J=5.3, 1H), 5.83 (dq, J=10.1, 6.1 Hz, 1H), 4.52 (dq, J=8.1, 7.2 Hz, 1H), 4.06 (d, J=10.2 Hz, 1H), 3.93 (s, 3H), 1.26 (d, J=6.1 Hz, 3H), 0.97 (d, J=7.2 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 171.67, 168.53, 155.34, 148.72, 141.38, 141.13, 140.40, 130.48, 128.80, 128.50, 128.10, 128.03, 126.95, 126.70, 109.39, 73.57, 57.93, 56.07, 47.85, 19.24, 17.61; HRMS-ESI (m/Z) ([M+H].sup.+) calcd for C.sub.25H.sub.27N.sub.2O.sub.5, 435.1920; found, 435.1925.

Example 6A: Preparation of (S)—(S)-1,1-diphenylpropan-2-yl 2-(3-acetoxy-4-methoxypicolinamido)propanoate

(99) ##STR00040##

(100) To a solution of (S)—(S)-1,1-diphenylpropan-2-yl 2-(3-hydroxy-4-methoxypicolinamido)-propanoate (Cmpd 90; 70.0 mg, 0.161 mmol), Et.sub.3N (44.9 μL, 0.332 mmol), and DMAP (3.94 mg, 0.032 mmol) in DCM (3.2 mL) was added acetyl chloride (17.2 μL, 0.242 mmol) at room temperature, and the reaction mixture was stirred for 2 h. The solvent was evaporated, and the resulting crude oil was purified by flash column chromatography (SiO.sub.2, 1.fwdarw.40% acetone in hexanes) to afford the title compound (75.0 mg, 97%) as a colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.41 (d, J=7.8 Hz, J H), 8.30 (d, J=5.4 Hz, 1H), 7.38-7.10 (m, 10H), 6.97 (d, J=5.4 Hz, 1H), 5.82 (dq, J=10.0, 6.2 Hz, 1H), 4.52 (dt, J=8.2, 7.1 Hz, 1H), 4.05 (d, J=10.1 Hz, 1H), 3.87 (s, 3H), 2.37 (s, 3H), 1.24 (d, J=6.1 Hz, 3H), 0.89 (d, J=7.1 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 172.23, 168.89, 162.28, 159.42, 146.66, 141.55, 141.44, 141.25, 137.45, 128.77, 128.50, 128.13, 128.11, 126.89, 126.67, 109.73, 73.32, 57.90, 56.27, 47.85, 20.75, 19.25, 17.92; HRMS-ESI (m/z) ([M+H].sup.+) calcd for C.sub.27H.sub.29N.sub.2O.sub.6, 477.2025; found, 477.2019.

Example 6B: Preparation of (S)—(S)-1,1-diphenylpropan-2-yl 2-(3-(acetoxymethoxy)-4-methoxypicolinamido)propanoate

(101) ##STR00041##

(102) To a suspension of (S)—(S)-1,1-diphenylpropan-2-yl 2-(3-hydroxy-4-methoxypicolinamido)-propanoate (Cmpd 90; 100 mg, 0.230 mmol) and K.sub.2CO.sub.3 (63.6 mg, 0.460 mmol) in acetone (4.6 mL) was added bromomethyl acetate (33.9 μL, 0.345 mmol) at room temperature, and the mixture was heated to 55° C. for 3 h and then cooled to room temperature. The solvent was evaporated and the resulting crude material was purified by flash column chromatography (SiO.sub.2, 1.fwdarw.40% acetone in hexanes) to afford the title compound (94.0 mg, 80% yield) as a colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.25 (d, J=5.4 Hz, 1H), 8.22 (d, J=7.9 Hz, 1H), 7.34-7.09 (m, 1H), 6.92 (d, J=5.4 Hz, 1H), 5.83 (dq, J=10.1, 6.2 Hz, 1H), 5.72 (d, J=0.7 Hz, 2H), 4.60-4.49 (m, 1H), 4.06 (d, J=10.1 Hz, 1H), 3.88 (s, 3H), 2.05 (s, 3H), 1.25 (d, J=6.1 Hz, 3H), 0.91 (d, J=7.2 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 172.33, 170.25, 162.88, 160.24, 145.70, 143.91, 142.54, 141.48, 141.25, 128.76, 128.49, 128.12, 128.09, 126.89, 126.65, 109.56, 89.50, 73.27, 57.92, 56.17, 48.07, 20.86, 19.25, 17.73; HRMS-ESI (m/z) [M+H].sup.+ calcd for C.sub.28H.sub.31N.sub.2O.sub.7, 507.2131; found, 507.2125.

Example 6C: Preparation of (S)—(S)-1,1-diphenylpropan-2-yl 2-(3-((isobutyryloxy)methoxy)-4-methoxypicolinamido)propanoate

(103) ##STR00042##

(104) To a solution of (S)—(S)-1,1-diphenylpropan-2-yl 2-(3-hydroxy-4-methoxypicolinamido)-propanoate (Cmpd 90: 100 mg, 0.230 mmol) in acetone (4.6 mL) were added sodium carbonate (Na.sub.2CO.sub.3; 73.2 mg, 0.690 mmol), sodium iodide (NaI; 6.90 mg, 0.046 mmol) and chloromethyl 2-ethoxyacetate (62.9 mg, 0.460 mmol). The mixture was heated to 55° C. overnight and then cooled to room temperature, and the solvent was evaporated. The resulting residue was purified by flash column chromatography (SiO.sub.2, 2.fwdarw.30% acetone in hexanes) to afford the title compound (79.0 mg, 64%) as a colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.28 (d, J=7.9 Hz, 1H), 8.25 (d, J=5.3 Hz, 1H), 7.36-7.08 (m, 10H), 6.92 (d, J=5.4 Hz, 1H), 5.83 (dq, J=10.1, 6.2 Hz, 1H), 5.79-5.69 (m, 2H), 4.62-4.44 (m, 1H), 4.06 (d, J=10.1 Hz, 1H), 3.86 (s, 3H), 2.53 (hept, J=7.0 Hz, 1H), 1.25 (d, J=6.2 Hz, 3H), 1.13 (d, J=7.0 Hz, 6H), 0.91 (d, J=7.2 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 176.22, 172.34, 162.85, 160.23, 145.55, 144.16, 142.18, 141.48, 141.26, 128.76, 128.49, 128.12, 128.09, 126.89, 126.65, 109.48, 89.90, 73.26, 57.93, 56.12, 48.07, 33.85, 19.26, 18.68, 17.74; HRMS-ESI (m/z) ([M+H].sup.+) calcd for C.sub.30H.sub.35N.sub.2O.sub.7, 535.2444; found, 535.2431.

Example A: Evaluation of Fungicidal Activity: Leaf Blotch of Wheat (Zymoseptoria tritici; Bayer Code SEPTTR)

(105) Technical grades of materials were dissolved in acetone, which were then mixed with nine volumes of water (H.sub.2O) containing 110 ppm Triton X-100. The fungicide solutions were applied onto wheat seedlings using an automated booth sprayer to run-off. All sprayed plants were allowed to air dry prior to further handling. All fungicides were evaluated using the aforementioned method for their activity vs. all target diseases, unless stated otherwise. Wheat leaf blotch and brown rust activity were also evaluated using track spray applications, in which case the fungicides were formulated as EC formulations, containing 0.1% Trycol 5941 in the spray solutions.

(106) Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Zymoseptoria tritici either prior to or after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. When disease symptoms were fully expressed on the 1.sup.st leaves of untreated plants, infection levels were assessed on a scale of 0 to 100 percent disease severity. Percent disease control was calculated using the ratio of disease severity on treated plants relative to untreated plants.

Example B: Evaluation of Fungicidal Activity: Wheat Brown Rust (Puccinia Triticina; Synonym: Puccinia Recondita f. Sp. Tritici; Bayer Code PUCCRT)

(107) Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Puccinia triticina either prior to or after fungicide treatments. After inoculation the plants were kept in a dark dew room at 22° C. with 100% relative humidity overnight to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 24° C. for disease to develop. Fungicide formulation, application and disease assessment followed the procedures as described in the Example A.

Example C: Evaluation of Fungicidal Activity: Wheat Glume Blotch (Leptosphaeria nodorum; Bayer code LEPTNO)

(108) Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Leptosphaeria nodorum 24 h after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. Fungicide formulation, application and disease assessment followed the procedures as described in the Example A.

Example D: Evaluation of Fungicidal Activity: Apple Scab (Venturia inaequalis; Bayer Code VENTIN)

(109) Apple seedlings (variety McIntosh) were grown in soil-less Metro mix, with one plant per pot. Seedlings with two expanding young leaves at the top (older leaves at bottom of the plants were trimmed) were used in the test. Plants were inoculated with a spore suspension of Venturia inaequalis 24 h after fungicide treatment and kept in a 22° C. dew chamber with 100% relative humidity for 48 h, and then moved to a greenhouse set at 20° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.

Example E: Evaluation of Fungicidal Activity: Leaf Spot of Sugar Beets (Cercospora beticola; Bayer code CERCBE)

(110) Sugar beet plants (variety HH88) were grown in soil-less Metro mix and trimmed regularly to maintain a uniform plant size prior to test. Plants were inoculated with a spore suspension 24 h after fungicide treatments. Inoculated plants were kept in a dew chamber at 22° C. for 48 h then incubated in a greenhouse set at 24° C. under a clear plastic hood with bottom ventilation until disease symptoms were fully expressed. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.

Example F: Evaluation of Fungicidal Activity: Asian Soybean Rust (Phakopsora Pachyrhizi; Bayer Code PHAKPA)

(111) Technical grades of materials were dissolved in acetone, which were then mixed with nine volumes of H.sub.2O containing 0.011% Tween 20. The fungicide solutions were applied onto soybean seedlings using an automated booth sprayer to run-off. All sprayed plants were allowed to air dry prior to further handling.

(112) Soybean plants (variety Williams 82) were grown in soil-less Metro mix, with one plant per pot. Two weeks old seedlings were used for testing. Plants were inoculated either 3 days prior to or 1 day after fungicide treatments. Plants were incubated for 24 h in a dark dew room at 22° C. and 100% relative humidity then transferred to a growth room at 23° C. for disease to develop. Disease severity was assessed on the sprayed leaves.

Example G: Evaluation of Fungicidal Activity: Barley Scald (Rhyncosporium Secalis; Bayer Code RHYNSE)

(113) Barley seedlings (variety Harrington) were propagated in soil-less Metro mix, with each pot having 8 to 12 plants, and used in the test when the first leaf was fully emerged. Test plants were inoculated by an aqueous spore suspension of Rhyncosporium secalis 24 h after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 h. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.

Example H: Evaluation of Fungicidal Activity: Rice Blast (Pyricularia Oryzae; Bayer Code PYRIOR)

(114) Rice seedlings (variety Japonica) were propagated in soil-less Metro mix, with each pot having 8 to 14 plants, and used in the test when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Pyricularia oryzae 24 h after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 h to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 24° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.

Example I: Evaluation of Fungicidal Activity: Tomato Early Blight (Alternaria Solani; Bayer Code ALTESO)

(115) Tomato plants (variety Outdoor Girl) were propagated in soil-less Metro mix, with each pot having one plant, and used when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Alternaria solani 24 h after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 h to permit spores to germinate and infect the leaf. The plants were then transferred to a growth room at 22° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.

Example J: Evaluation of Fungicidal Activity: Cucumber Anthracnose (Collelotrichum lagenarium; Bayer Code COLLLA)

(116) Cucumber seedlings (variety Bush Pickle) were propagated in soil-less Metro mix, with each pot having one plant, and used in the test when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Colletotrichum lagenarium 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a growth room set at 22° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.

(117) TABLE-US-00001 TABLE 1 Compound Structure, Preparation Method, and Appearance Prepared According *Cmpd. To No. Structure Example Appearance 1 Example 1; Example 3A; Example 4A White Solid 2 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 3 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 4 Example 1; Example 2A; Example 3A; Example 4A Clear, Colorless Oil 5 Example 1; Example 2B; Example 3A; Example 4A Colorless Oil 6 Example 1; Example 2B; Example 3A; Example 4A Colorless Oil 7 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 8 0 Example 1; Example 2C; Example 3A; Example 4A Colorless Oil 9 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 10 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 11 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 12 Example 3E; Example 4A Colorless Oil 13 Example 3E; Example 4A Colorless Oil 14 Example 1; Example 3C; Example 4A Colorless Oil 15 Example 1; Example 3C; Example 4A Colorless Oil 16 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 18 Example 3F; Example 4A Colorless Oil 19 0 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 20 Example 1; Example 2A; Example 3A; Example 4A Clear Oil 21 Example 1; Example 2A; Example 3A; Example 4A Clear Oil 22 Example 1; Example 2A; Example 3A; Example 4A Clear Oil 23 Example 1; Example 2A; Example 3A; Example 4A Clear Oil 24 Example 1; Example 3C; Example 4A Sticky Wax 25 Example 1; Example 3C; Example 4A Sticky Wax 26 Example 1; Example 3C; Example 4A Sticky Wax 27 Example 1; Example 3C; Example 4A Sticky Wax 28 Example 1; Example 3C; Example 3D, Steps 1-2; Example 4A White Foam 29 0 Example 1; Example 3C; Example 3D, Steps 1-3; Example 4A Sticky Wax 31 Example 3F; Example 4A Clear Oil 33 Example 1; Example 3B; Example 4A White Solid 34 Example 1; Example 3B; Example 4A White Solid 35 Example 1; Example 2A; Example 3A; Example 4A White Solid 36 Example 1; Example 3B; Example 4A White Foam 37 Example 1; Example 2A; Example 3A; Example 4A Clear, Colorless Oil 38 Example 1; Example 2A; Example 3A; Example 4A Clear, Colorless Oil 39 Example 1; Example 2A; Example 3A; Example 4A Clear, Colorless Oil 40 Example 1; Example 2A; Example 3A; Example 4A White Foam 43 0 Example 1; Example 2A; Example 3A; Example 4A White Solid 44 Example 1; Example 2A; Example 3A; Example 4A White Solid 45 Example 5, Step 1 White Solid 46 Example 5, Step 1 Colorless Oil 47 Example 5, Step 1 Colorless Oil 48 Example 5, Step 1 Pale Yellow Oil 49 Example 5, Step 1 Colorless Oil 50 Example 5, Step 1 Colorless Oil 51 Example 5, Step 1 Colorless Oil 52 Example 5, Step 1 Colorless Oil 53 0 Example 5, Step 1 Colorless Oil 54 Example 5, Step 1 Colorless Oil 55 Example 5, Step 1 Colorless Oil 56 Example 5, Step 1 Colorless Oil 57 Example 5, Step 1 Colorless Oil 58 Example 5, Step 1 Colorless Oil 59 Example 5, Step 1 Colorless Oil 60 Example 5, Step 1 Colorless Oil 61 Example 5, Step 1 White Solid 63 Example 5, Step 1 Colorless Oil 64 00 Example 5, Step 1 Colorless Oil 65 01 Example 5, Step 1 Sticky Oil 66 02 Example 5, Step 1 Sticky Oil 67 03 Example 5, Step 1 Sticky Oil 68 04 Example 5, Step 1 Sticky Wax 69 05 Example 5, Step 1 Sticky Wax 70 06 Example 5, Step 1 Sticky Wax 71 07 Example 5, Step 1 White Solid 72 08 Example 5, Step 1 White Solid 73 09 Example 5, Step 1 White Solid 74 0 Example 5, Step 1 White Solid 75 Example 5, Step 1 White Solid 77 Example 5, Step 1 White Solid 78 Example 5, Step 1 White Solid 79 Example 5, Step 1 White Solid 80 Example 1; Example 3B; Example 4A; Example 5, Step 1 Sticky Oil 81 Example 5, Step 1 Sticky Oil 83 Example 5, Step 1 Colorless Oil 84 Example 5, Step 1 Clear, Colorless Oil 85 Example 5, Step 1 Clear, Colorless Oil 86 0 Example 5, Step 1 White Solid 87 Example 5, Step 1 White Solid 88 Example 5, Step 1 White Solid 89 Example 5, Step 2 White Solid 90 Example 5, Step 2 White Foam 91 Example 5, Step 2 Colorless Oil 92 Example 5, Step 2 White Foam 93 Example 5, Step 2 White Foam 95 Example 5, Step 2 Colorless Oil 96 Example 5, Step 2 White Foam 97 0 Example 5, Step 2 Colorless Oil 98 Example 5, Step 2 Colorless Oil 99 Example 5, Step 2 Colorless Oil 100 Example 5, Step 2 Colorless Oil 101 Example 5, Step 2 Colorless Oil 102 Example 5, Step 2 Colorless Oil 103 Example 5, Step 2 Colorless Oil 104 Example 5, Step 2 Colorless Oil 105 Example 5, Step 2 Colorless Oil 106 Example 5, Step 2 Colorless Gel 107 0 Example 5, Step 2 Colorless Gel 109 Example 5, Step 2 Colorless Oil 110 Example 5, Step 2 Clear, Colorless Oil 111 Example 5, Step 2 Clear, Colorless Oil 112 Example 5, Step 2 Clear, Colorless Oil 113 Example 5, Step 2 White Solid 114 Example 5, Step 2 White Solid 115 Example 5, Step 2 White Solid 116 Example 5, Step 2 White Solid 117 Example 5, Step 2 White Foam 118 0 Example 5, Step 2 White Foam 119 Example 5, Step 2 White Foam 120 Example 5, Step 2 White Foam 121 Example 5, Step 2 White Foam 122 Example 5, Step 2 White Foam 123 Example 5, Step 2 White Foam 124 Example 5, Step 2 White Foam 125 Example 5, Step 2 White Solid 127 Example 5, Step 2 White Solid 128 Example 5, Step 2 White Solid 129 0 Example 5, Step 2 White Solid 130 Example 5, Step 2 Clear, Colorless Oil 131 Example 5, Step 2 Clear, Colorless Oil 132 Example 5, Step 2 Colorless Foam 133 Example 5, Step 2 Colorless Foam 135 Example 5, Step 2 Colorless Tacky Semi- Solid 136 Example 5, Step 2 White Foam 137 Example 5, Step 2 White Foam 138 Example 6B Colorless Semi-Solid 139 Example 6A Colorless Oil 140 0 Example 6A White Foam 141 Example 6B White Foam 142 Example 6C White Foam 143 Example 6A Colorless Oil 144 Example 6B Colorless Oil 145 Example 6A Colorless Oil 146 Example 6B Colorless Oil 147 Example 6B Colorless Oil 148 Example 6B Colorless Oil 149 Example 6B Colorless Oil 150 0 Example 6A Colorless Oil 152 Example 6A Colorless Oil 153 Example 6B Colorless Oil 155 Example 6A Colorless Oil 156 Example 6A Colorless Oil 157 Example 6A Colorless Oil 158 Example 6B Colorless Oil 159 Example 6B Colorless Oil 160 Example 6B Colorless Oil 161 Example 6A Colorless Oil 162 0 Example 6A Colorless Oil 163 Example 6B Colorless Oil 164 Example 6B Colorless Oil 165 Example 6A Colorless Oil 166 Example 6A Colorless Oil 167 Example 6A Colorless Oil 168 Example 6A Colorless Oil 169 Example 6B Colorless Oil 170 Example 6B Colorless Oil 171 Example 6B Colorless Oil 173 00 Example 6A Colorless Oil 174 01 Example 6A Colorless Oil 175 02 Example 6B Colorless Oil 176 03 Example 6B Colorless Oil 178 04 Example 6B Clear, Colorless Oil 179 05 Example 6B Clear, Colorless Oil 180 06 Example 6B Clear, Colorless Oil 181 07 Example 6B White Foam 182 08 Example 6A Colorless Oil 183 09 Example 6B White Solid 184 0 Example 6B White Solid 185 Example 6B White Solid 186 Example 6B White Solid 187 Example 6A White Solid 188 Example 6A White Solid 189 Example 6A White Solid 190 Example 6A White Solid 191 Example 6B White Solid 192 Example 6B While Foam 193 Example 6B Sticky Wax 194 0 Example 6B White Foam 195 Example 6B White Foam 196 Example 6B White Foam 197 Example 6B White Foam 198 Example 6B Sticky Wax 199 Example 6B White Solid 201 Example 6B White Solid 202 Example 6B White Solid 203 Example 6B White Solid 204 Example 6A White Solid 206 0 Example 6A White Solid 207 Example 6A White Solid 208 Example 6A Clear Colorless Oil 209 Example 6A Slightly Cloudy Colorless Oil 210 Example 6A Slightly Cloudy Colorless Oil 211 Example 6C Clear Colorless Oil 212 Example 6C Colorless Clear Film And Opaque Oil 213 Example 6A Clear Colorless Viscous Oil And Semi- Solid 214 Example 6B Clear, Colorless Oil 215 Example 6A Pale Yellow Oil 216 0 Example 6A Pale Yellow Oil 217 Example 6A Pale Yellow Oil 218 Example 6B Pale Yellow Oil 219 Example 6B Pale Yellow Oil 220 Example 6B Pale Yellow Oil 221 Example 6B While Foam 222 Example 6B While Foam 223 Example 6A While Foam 224 Example 6A While Foam 225 Example 6B Slightly Opaque Colorless Oil 226 0 Example 1; Example 2D, Steps 1- 2; Example 3A; Example 4A While Semi- Solid 227 Example 5, Step 1 White Glass 228 Example 5, Step 2 Colorless Foam 229 Example 6A Clear, Colorless Oil 230 Example 6B Clear, Colorless Oil 232 Example 5, Step 1 White Semi- Solid 233 Example 1; Example 2A; Example 3A; Example 4A Clear, Colorless Viscous Oil 234 Example 1; Example 2A; Example 3A; Example 4A. Clear, Colorless Oil 235 Example 1; Example 2A; Example 3A; Example 4A. Clear, Colorless Oil 236 Example 1; Example 2A; Example 3A; Example 4A. Clear, Colorless Oil 237 0 Example 1; Example 2A; Example 3A; Example 4A. Clear, Colorless Oil 238 Example 1; Example 2A; Example 3A; Example 4A. Slightly Cloudy Colorless Viscous Oil 239 Example 1; Example 2A; Example 3A; Example 4A. Slightly Cloudy Colorless Viscous Oil 240 Example 1; Example 2A; Example 3A; Example 4A. White Foam 241 Example 3H Steps 1-2; Example 4A. Colorless Oil 242 Example 3G, Steps 1 and 2; Example 4A Colorless Oil 243 Example 3G, Steps 1 and 2; Example 4A Colorless Oil 244 Example 4A Colorless Oil 245 Example 1; Example 3C; Exasnple 4A. White Foam 246 Example 1; Example 2A; Example 3A; Example 4A. White Foam 247 0 Example 1; Example 3C; Example 4A. White Foam 248 Example 1; Example 2A; Example 3A; Example 4A. White Foam 249 Example 3G, Steps 1 and 2; Example 4A White Foam 250 Example 1; Example 2A; Example 3A; Example 4A. White Semisolid 251 Example 1; Example 2A; Example 3A; Example 4A. White Semisolid 252 Example 1; Example 2A; Example 3A; Example 4A. White Semisolid 253 Example 1; Example 2A; Example 3A; Example 4A. Clear, Colorless Oil 254 Example 1; Example 2A; Example 3A; Example 4A. Clear, Colorless Oil 255 Example 1; Example 2A; Example 3A; Example 4A. Clear, Colorless Oil 256 Example 1; Example 2A; Example 3A; Example 4A. Clear, Colorless Oil 257 0 Example 1; Example 2A; Example 3A; Example 4A. Clear, Colorless Oil 258 Example 3I; Example 4A White Foam 259 Example 1; Example 2A; Example 3A; Example 4A. White Foam 260 Example 1; Example 2A; Example 3A; Example 4A. Colorless Oil 261 Example 1; Example 2A; Example 3A; Example 4A. Colorless Oil 262 Example 1; Example 2A; Example 3A; Example 4A. Colorless Oil 263 Example 1; Example 2A; Example 3A; Example 4A. Colorless Oil 264 Example 1; Example 2A; Example 3A; Example 4A. White Foam 265 Example 1; Example 2A: Example 3A; Example 4A. Colorless Oil 266 Example 1; Example 2A; Example 3A; Example 4A. Sticky Wax 267 0 Example 1; Example 2A; Example 3A; Example 4A. Sticky Wax. 268 Example 3I, Example 4A Oil 269 Example 3I, Example 4A Oil 270 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 271 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 272 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 273 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 274 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 275 Example 3F; Example 4A Colorless Oil 276 Example 3F; Example 4A Colorless Oil 277 00 Example 3F; Example 4A Colorless Oil 278 01 Example 3F; Example 4A Colorless Oil 279 02 Example 3F; Example 4A Colorless Oil 280 03 Example 3F; Example 4A Colorless Oil 281 04 Example 3F; Example 4A Colorless Oil 282 05 Example 3F; Example 4A Colorless Oil 283 06 Example 3F; Example 4A Colorless Oil 284 07 Example 3F; Example 4A Colorless Oil 285 08 Example 3F; Example 4A Colorless Oil 286 09 Example 3F; Example 4A Colorless Oil 287 0 Example 3F; Example 4A Colorless Oil 288 Example 3F; Example 4A White Foam 289 Example 3F; Example 4A Yellow Sticky Wax 290 Example 3F; Example 4A White Foam 291 Example 3F; Example 4A Yellow Sticky Wax 292 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 293 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 294 Example 1; Example 2A; Example 3A; Example 4A Colorless Oil 295 Example 3F; Example 4A Colorless Oil 296 Example 3F; Example 4A Colorless Oil 297 0 Example 3F; Example 4A Colorless Oil 298 Example 3F; Example 4A Colorless Oil 299 Example 3F; Example 4A Colorless Oil 300 Example 3F; Example 4A Colorless Oil 301 Example 3F; Example 4A Colorless Oil 302 Example 3F; Example 4A Colorless Oil 303 Example 3F; Example 4A Colorless Oil 304 Example 3F; Example 4A Colorless Oil 305 Example 3F; Example 4A Colorless Oil 306 Example 3F; Example 4A Colorless Oil 307 0 Example 3F; Example 4A Colorless Oil 308 Example 3F; Example 4A Thick Oil 309 Example 3F; Example 4A Colorless Oil 310 Example 5, Step 1. White Powder 311 Example 5, Step 1. White Powder 312 Example 5, Step 1. Clear, Colorless Thick Oil 313 Example 5, Step 1. White Powder 314 Example 5, Step 1. White Semi- Solid 315 Example 5, Step 1. White Semi- Solid 316 Example 5, Step 1. Clear Glass 317 0 Example 1; Example 2A; Example 3A; Example 4A. Example 5, step 1. Pale Purple Sticky Wax 318 Example 5 Step 1. Colorless Oil 319 Example 5, Step 1 White Foam 320 Example 5, Step 1 White Foam 321 Example 5, Step 1 White Solid 322 Example 5, Step 1. Colorless Oil 323 Example 5, Step 1. Yellow Oil 324 Example 5, Step 1. Yellow Oil 325 Example 5, Step 1. Yellow Oil 326 Example 5, Step 1. Yellow Oil 327 0 Example 5, Step 1 White Foam 328 Example 5, Step 1 White Foam 329 Example 5, Step 1 White Foam 330 Example 5, Step 1 White Foam 331 Example 5, Step 1 White Foam 332 Example 5, Step 1 Clear, Colorless Oil 333 Example 5, Step 1. Light Brown Oil 334 Example 5, Step 1. Pale Yellow Oil 335 Example 5, Step 1. Pale Yellow Oil 336 Example 5, Step 1. White Powdery Solid 337 0 Example 5, Step 1. Clear, Colorless Oil 338 Example 5, Step 1. Whitc Powdery Solid 339 Example 5, Step 1. Clear, Colorless Oil 340 Example 5, Step 1. Whitc Solid 341 Example 5, Step 1. Thick Oil 342 Example 5, Step 1. White Solid 343 Example 5, Step 1. White Solid 344 Example 5, Step 1. White Solid 345 Example 5, Step 1. White Solid 346 Example 5, Step 1. Thick Oil 347 0 Example 5, Step 1. White Solid 348 Example 5, Step 1. White Solid 349 Example 5, Step 1 Oil 350 Example 5, Step 1 Oil 351 Example 5, Step 1 Oil 352 Example 5, Step 1 Colorless Oil 353 Example 5, Step 1 Colorless Oil 354 Example 5, Step 1 Colorless Oil 355 Example 5, Step 1 Colorless Oil 356 Example 5, Step 1 Colorless Oil 357 0 Example 5, Step 1 Colorless Oil 358 Example 5, Step 1 Colorless Oil 359 Example 5, Step 1 Colorless Oil 360 Example 5, Step 1 Colorless Oil 361 Example 5, Step 1 Colorless Foam 362 Example 5, Step 1 Colorless Foam 363 Example 5, Step 1 Colorless Oil 364 Example 5, Step 1 Colorless Oil 365 Example 5, Step 1 White Foam 366 Example 5, Step 1. Sticky Wax 367 0 Example 5, Step 1. Sticky Wax 368 Example 5, Step 1. Sticky Wax 369 Example 5, Step 1. Sticky Wax 370 Example 5, Step 1. White Foam 371 Example 5, Step 1 White Foam 372 Example 5, Step 1 White Foam 373 Example 5, Step 1 White Foam 374 Example 5, Step 1 White Foam 375 Example 5, Step 1 Colorless Oil 376 Example 5, Step 1 Colorless Oil 377 00 Example 5, Step 1. Thick Oil 378 01 Example 5, Step 1. Thick Oil 379 02 Example 5, Step 1. White Solid 380 03 Example 5, Step 1. Thick Oil 381 04 Example 5, Step 1. Thick Oil 382 05 Example 5, Step 1. White Foam 383 06 Example 5, Step 1. White Solid 384 07 Example 5, Step 1. White Foam 385 08 Example 5, Step 1. White Foam 386 09 Example 5 Step 2. Matte White Solid And Clear Oil 387 0 Example 5 Step 2. Matte White Solid And Clear Oil 388 Example 5, Step 2. Clear, Colorless Oil 389 Example 5, Step 2. Colorless Foam 390 Example 5, Step 2. Colorless Foam 391 Example 5, Step 2. Clear, Colorless Oil 392 Example 5, Step 2. Semi Solid 393 Example 5, Step 2. White Foam 394 Example 5 Step 2. Colorless Foamy Oil 395 Example 5, Step 2. White Foam 396 Example 5, Step 2 White Foam 397 0 Example 5, Step 2 White Foam 398 Example 5, Step 2 White Foam 399 Example 5, Step 2. White Foam 400 Example 5, Step 2. White Foam 401 Example 5, Step 2. White Foam 402 Example 5, Step 2. White Foam 403 Example 5, Step 2 Colorless Oil 404 Example 5, Step 2 Colorless Oil 405 Example 5, Step 2 White Foam 406 Example 5, Step 2 White Foam 407 0 Example 5, Step 2 White Foam 408 Example 5, Step 2 White Foam 409 Example 5, Step 2 White Foam 410 Example 5, Step 2 White Foam 411 Example 5, Step 2 White Foam 412 Example 5, Step 2 Oil 413 Example 5, Step 2. White Foam 414 Example 5, Step 2. Thick Oil 415 Example 5, Step 2. White Foam 416 Example 5, Step 2. White Foam 417 0 Example 5, Step 2. White Foam 418 Example 5, Step 2. White Foam 419 Example 5, Step 2. White Foam 420 Example 5, Step 2. Colorless Foam 421 Example 5, Step 2. Clear, Colorless Oil 422 Example 5, Step 2. Clear, Colorless Oil 423 Example 5, Step 2. Colorless Foam 424 Example 5, Step 2. Colorless Foam 425 Example 5, Step 2. Clear, Colorless Oil 426 Example 5, Step 2. Clear, Colorless Oil 427 0 Example 5, Step 2. Clear, Colorless Oil 428 Example 5, Step 2. White Foam 429 Example 5, Step 2. Sticky Wax 430 Example 5, Step 2 Colorless Gel 431 Example 5, Step 2 Colorless Gel 432 Example 5, Step 2 Colorless Gel 433 Example 5, Step 2 Colorless Gel 434 Example 5, Step 2 Colorless Oil 435 Example 5, Step 2 Colorless Oil 436 Example 5, Step 2 Colorless Oil 437 0 Example 5, Step 2 Colorless Oil 438 Example 5, Step 2 Colorless Foam 439 Example 5, Step 2 Colorless Foam 440 Example 5, Step 2 Colorless Oil 441 Example 5, Step 2 Colorless Oil 442 Example 5, Step 2 White Foam 443 Example 5, Step 2. White Foam 444 Example 5, Step 2. White Foam 445 Example 5, Step 2. White Foam 446 Example 5, Step 2. White Foam 447 0 Example 5, Step 2 White Foam 448 Example 5, Step 2 White Foam 449 Example 5, Step 2 White Foam 450 Example 5, Step 2 White Foam 451 Example 5, Step 2 White Foam 452 Example 5, Step 2 Colorless Oil 453 Example 5, Step 2 Colorless Oil 454 Example 5, Step 2. White Foam 455 Example 5, Step 2. White Foam 456 Example 5, Step 2. White Foam 457 0 Example 5, Step 2. White Foam 458 Example 5, Step 2. White Foam 459 Example 5, Step 2. White Foam 460 Example 5, Step 2. White Foam 461 Example 5, Step 2. White Foam 462 Example 6B. Slightly Opaque Colorless Viscous Oil 463 Example 6B. White Foam Slightly Opaque Colorless Viscous Oil 464 Example 6B. Yellow Oil 465 Example 6B. Clear, Colorless Oil 466 Example 6B. Pale Yellow Oil 467 0 Example 6B. Pale Yellow Oil 468 Example 6A. Fluffy White Powder 469 Example 6A. Clear, Colorless Oil 470 Example 6A. Clear, Colorless Oil 471 Example 6A. Clear, Colorless Oil 472 Example 6B. White Foam 473 Example 6B. Sticky Wax 474 Example 6B. Colorless Oil 475 Example 6A. White Foam 476 Example 6B. White Foam 477 00 Example 6A. White Foam 478 01 Example 6A. White Foam 479 02 Example 6A. White Foam 480 03 Example 6B. White Foam 481 04 Example 6B. White Foam 482 05 Example 6B. White Foam 483 06 Example 6B. White Foam 484 07 Example 6B. White Foam 485 08 Example 6A Colorless Oil 486 09 Example 6A Colorless Oil 487 0 Example 6B Colorless Oil 488 Example 6A. White Foam 489 Example 6A. White Foam 490 Example 6A. White Wax 491 Example 6A. White Foam 492 Example 6A. White Foam 493 Example 6B White Foam 494 Example 6C White Foam 495 Example 6A White Foam 496 Example 6A White Foam 497 0 Example 6A Colorless Film 498 Example 6A. White Foam 499 Example 6A. White Foam 500 Example 6A. White Foam 501 Example 6A. White Foam 502 Example 6A. White Foam 503 Example 6A. White Foam 504 Example 6A. White Foam 505 Example 6A. Clear, Colorless Oil 506 Example 6A. Clear, Colorless Oil 507 0 Example 6A. Clear, Colorless Oil 508 Example 6A. Clear, Colorless Oil 509 Example 6A. Clear, Colorless Oil 510 Example 6A. Clear, Colorless Oil 511 Example 6A. Clear, Colorless Oil 512 Example 6A. Clear, Colorless Oil 513 Example 6B. Clear, Colorless Oil 514 Example 6B. Clear, Colorless Oil 515 Example 6B. Clear, Colorless Oil 516 Example 6B. Clear, Colorless Oil 517 0 Example 6B. Clear, Colorless Oil 518 Example 6B. Clear, Colorless Oil 519 Example 6B. Clear, Colorless Oil 520 Example 6B. Clear, Colorless Oil 521 Example 6A. White Foam. 522 Example 6A. Sticky White Foam 523 Example 6A Colorless Oil 524 Example 6A Colorless Oil 525 Example 6A Colorless Oil 526 Example 6A Colorless Oil 527 0 Example 6A Colorless Foam 528 Example 6A Colorless Foam 529 Example 6A Colorless Foam 530 Example 6A Colorless Foam 531 Example 6A Colorless Oil 532 Example 6A Colorless Oil 533 Example 6A Colorless Oil 534 Example 6A Colorless Oil 535 Example 6A. White Foam 536 Example 6A. White Foam 537 0 Example 6A. White Foam 538 Example 6A. White Foam 539 Example 6A. White Foam 540 Example 6A. White Foam 541 Example 6A. White Foam 542 Example 6A. White Foam 543 Example 6A. White Foam 544 Example 6A. White Foam 545 Example 6A. White Foam 546 Example 6A. White Foam 547 0 Example 6A. White Foam 548 Example 6A. White Foam 549 Example 6A. White Foam 550 Example 6A. White Foam 551 Example 6A. White Foam 552 Example 6A. White Foam 553 Example 6A Colorless Foam 554 Example 6A Colorless Foam *Cmpd. No.—Compound Number

(118) TABLE-US-00002 Lengthy table referenced here US11751568-20230912-T00001 Please refer to the end of the specification for access instructions.

(119) TABLE-US-00003 Lengthy table referenced here US11751568-20230912-T00002 Please refer to the end of the specification for access instructions.

(120) TABLE-US-00004 Lengthy table referenced here US11751568-20230912-T00003 Please refer to the end of the specification for access instructions.

(121) TABLE-US-00005 Lengthy table referenced here US11751568-20230912-T00004 Please refer to the end of the specification for access instructions.

(122) TABLE-US-00006 Lengthy table referenced here US11751568-20230912-T00005 Please refer to the end of the specification for access instructions.

(123) TABLE-US-00007 Lengthy table referenced here US11751568-20230912-T00006 Please refer to the end of the specification for access instructions.

(124) TABLE-US-LTS-00001 LENGTHY TABLES The patent contains a lengthy table section. A copy of the table is available in electronic form from the USPTO web site (). An electronic copy of the table will also be available from the USPTO upon request and payment of the fee set forth in 37 CFR 1.19(b)(3).