PICOLINAMIDE COMPOUNDS WITH FUNGICIDAL ACTIVITY

Abstract

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

##STR00001##

Claims

1-30. (canceled)

1. A compound of Formula I ##STR00043##

2. A method for the control and prevention of fungal attack on a plant, the method including the step of: applying a fungicidally effective amount of the compound of claim 1 to at least one of the plant, an area adjacent to the plant, soil adapted to support growth of the plant, a root of the plant, and foliage of the plant.

Description

EXAMPLES

[0079] The chemistry in the following examples may be conducted using either enantiomer of 2-((tert-butoxycarbonyl)amino)propanoic acid (BocAlaOH) 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

[0080] ##STR00016##

[0081] To a solution of (9-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 (M) 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 (250 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) 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) -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)

[0082] ##STR00017##

[0083] 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 (230 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) 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, 3.93 (d, J=8.1 Hz, 1H), 1.18 (d, J=6.0 Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3) 116.60, 117.10; ESIMS (m/z) 361 ([M+Na].sup.+).

Example 2B

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

[0084] ##STR00018##

[0085] 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 (MeI; 93.0 microliters (L), 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 (210 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) 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, 6.1 Hz, 3H); NMR (101 MHz, CDCl.sub.3) 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-diypdibenzene

[0086] ##STR00019##

[0087] 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 (210 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% acetone in hexanes) to afford the title compound (300 mg, 98%) as a colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) 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) 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) 159.80.

Example 2D, Step 1

Preparation of (S)-O-(2-(benzyloxy)-1,1-bis(3,4,5-trifluorophenyl)propyl) S-methyl carbonodithioate

[0088] ##STR00020##

[0089] 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 L, 9.30 mmol) was added via syringe in one portion, followed by MeI (579 L, 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 (310 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) 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); NMR (376 MHz, CDCl.sub.3) 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)

[0090] ##STR00021##

[0091] A solution of (5)-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, 0.fwdarw.30% EtOAc in hexanes) to afford the title compound (358 mg, 72%) as a clear, colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) 7.28 (d, J=6.6 Hz, 3B), 7.17-7.06 (m, 2H), 6.92 (dd, J=8.5, 6.5 Hz, 2H), 6,79 (d, 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) 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

[0092] ##STR00022##

[0093] 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) 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.3) 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) 115.84, 116.19.

Example 3B

Preparation of (S)-1,1-bis(2-fluorophenyl)propane-1,2-diol

[0094] ##STR00023##

[0095] 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) 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) 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

[0096] ##STR00024##

[0097] 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 (230 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 (742 mg, 56%) as a colorless oil: .sup.1 H NMR (300 MHz, CDCl.sub.3) 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) 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 (5)-1,1-bis ethylsilyl)ethynyl)phenyl)propan-2-ol

[0098] ##STR00025##

[0099] 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 trig, 45%) as a brown foam: .sup.1H NMR (400 MHz, CDCl.sub.3) 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, 914); .sup.13C NMR (101 MHz, CDCl.sub.3) 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

[0100] ##STR00026##

[0101] 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) 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) 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 (5)-1 ,l-bis(4-ethylphenyl)propan-2-ol

[0102] ##STR00027##

[0103] 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) 7.33-7.2.5 (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) 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.19O.sub.24NaO, 291.1719; found, 291.1725.

Example 3E

Preparation of 1-(9/1-xanthen-9-yl)ethanol

[0104] ##STR00028##

[0105] 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 (215 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) 7.33-7.22 (m, 4H), 7.17-7.04 (m, 4H), 3.99 (d, J=5.1 Hz, 1H), 396-3.82 (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) 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 (in/z) 475 ([2M+Na].sup.+).

Example 3F

Preparation of (1S,2S)-1-phenyl-1-(4-(trifluoromethyl)phenyl)propan-2-ol

[0106] ##STR00029##

[0107] 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 L). 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 (21.5 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 (390 mg, 94%) as a light yellow oil: .sup.1H NMR (400 MHz, CDCl.sub.3) 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) 62.49; ESIMS (m/z) 263 ([MOH].sup.+),

Example 3G, Step 1

Preparation of 4,4-(2-oxopropane-1,1dibenzonitrile

[0108] ##STR00030##

[0109] 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 (310 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) 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) 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

[0110] ##STR00031##

[0111] 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 0.067 mmol). Then, the reaction was cooled to 0 C. and a solution of BH.sub.3-DMS (69.8 l, 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 EtOAc2. 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) 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) 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].sup.+).

Example 3H, Step 1

Preparation of 3,3-diphenylbutan-2-one

[0112] ##STR00032##

[0113] 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 L, 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, 0.fwdarw.5% acetone in hexanes) to afford the title compound (330 mg, 71%) as a colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) 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) 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

[0114] ##STR00033##

[0115] 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 L, 0.134 mmol). Then, a solution of BH.sub.3-DMS (70.2 L, 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, 0.fwdarw.20% acetone in hexanes) to afford the title compound (150 mg, 99%) as a colorless oil: .sup.1H NMR, (400 MHz, CDCl.sub.3) 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) 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 31, Step 1

Preparation of (S)-1,1-bis(2,3-dimethoxyphenyl)propane-1,2-diol

[0116] ##STR00034##

[0117] 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) 7.43 (td, J=8.0, 1.5 Hz, 2H), 7.11 (td, J=8.1, 4.9 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) 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 31, Step 2

Preparation of 1,1-bis(2,3-dimethoxyphenyl)propan-2-one

[0118] ##STR00035##

[0119] 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 l, 4.82 mmol) and trifluoroacetic acid (TFA, 124 L, 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 L, 3.2. mmol) was added, and the reaction was then stirred overnight at it The reaction was diluted with water (25 mL) and extracted with CH.sub.2Cl.sub.2 (325 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.1 H NMR (300 MHz, CDCl.sub.3) 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) 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

[0120] ##STR00036##

[0121] 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 (320 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) 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) 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

[0122] ##STR00037##

[0123] 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) 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) 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 (9-1-(((S)-1,1-diphenylpropan-2-yl)oxy)-1-oxopropan-2-aminium chloride

[0124] ##STR00038##

[0125] 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

[0126] ##STR00039##

[0127] To a solution of (S)-14((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.fwdarw.50% acetone in hexanes) to afford the title compound (340 mg, 70%) as a white foam: .sup.1H NMR (400 MHZ, CDCl.sub.3) 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, 10H), 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) 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

[0128] ##STR00040##

[0129] To a solution of (S)-(9-1,1-diphenylpropan-2-yl 2(3-hydroxy-4-methoxypicolinamido)-propanoate (Cmpd 90; 70,0 mg, 0.161 mmol) Et.sub.3N (44.9 L, 0.332 mmol), and DMAP (3.94 mg, 0.032 mmol) in DCM (3.2 mL) was added acetyl chloride (17.2 L, 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) 8.41 (d, J 7.8 Hz, 1H), 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) 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 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-diphenytpropan-2-yl 2-(3-(acetoxymethoxy)-4-methoxypicolinamido)propanoate

[0130] ##STR00041##

[0131] 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 L, 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) 8.25 (d, J=5.4 Hz, 1H), 8.22 (d, J=7.9 Hz, 1H), 7.34 7.09 (m, 10H), 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) 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

[0132] ##STR00042##

[0133] 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) 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) 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)

[0134] 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.

[0135] 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)

[0136] 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 (Leptasphaeria nodorum; Bayer code LEPTNO)

[0137] 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)

[0138] 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 Venturi a lime quails 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 (Cercaspora beticola; Bayer code CERCBE)

[0139] 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)

[0140] 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.

[0141] 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)

[0142] 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 olyzae; Bayer code PYRIOR)

[0143] 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)

[0144] 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 (Colletotrichum lagenarium; Bayer code COLLLA):

[0145] 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 Colletotrichun 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.

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TABLE-US-LTS-00001 LENGTHY TABLES The patent application 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).