Hydrocarbon-Soluble Halogen and Thiolate/Magnesium Exchange Reagents

Abstract

The invention relates to hydrocarbon-soluble halogen or thiolate/magnesium exchange reagents of the general formula

R.sup.1MgR.sup.1.sub.1n(OR.sup.3).sub.n.Math.LiOR2.Math.(1n)LiOR.sup.3.Math.aDonor

in which: R.sup.1 is a C1-C8 alkyl and OR.sup.2 as well as OR.sup.3 are same or different and represent primary, secondary, or tertiary alkoxide residues having 3 to 18 carbon atoms, wherein R.sup.2 and/or R.sup.3 can for their part contain an alkoxy substituent OR.sup.4; a assumes a value of 0 to 2, n assumes a value between 0 and 1, and the donor is an organic molecule containing at least 2 nitrogen atoms.

Claims

1. Hydrocarbon-soluble exchange reagents of the general formula:
R.sup.1MgR.sup.1.sub.1n(OR.sup.3).sub.n.Math.LiOR.sup.2.Math.(1n) LiOR.sup.3.Math.aDonor wherein (i) R.sup.1 is a C.sub.1-C.sub.8 alkyl, (ii) OR.sup.2 and OR.sup.3 are the same or different and represent primary, secondary, or tertiary alkoxide residues having 3 to 18 carbon atoms, (iii) R.sup.2 and/or R.sup.3 contain an alkoxy substituent OR.sup.4; (iv) a has a value of 0 to 2, (v) n has a value from 0 to 1, and (vi) the Donor is an organic molecule containing at least 2 nitrogen atoms.

2. The hydrocarbon-soluble exchange reagents according to claim 1, characterized in that: OR.sup.2 and OR.sup.3 each are independently selected from the group consisting of: a) tert-alkoxy, b) sec-alkoxy, c) primary alkoxy OCH.sub.2CHR.sup.4R.sup.5, consisting of 3 to 12 carbon atoms, wherein the alkoxy residue has a branch at position 2 relative to the O-function and R.sup.4 and R.sup.5 independently represent alkyl radicals having 1 to 8 carbon atoms, and d) alkoxy, containing another alkoxy function, of the general formula O(CHR.sup.6).sub.bOR.sup.7 wherein R.sup.6=H or an alkyl radical having 1 to 6 carbon atoms, which is either linear or has a branch at position 3 or higher relative to the O-function, R.sup.7 s a linear or branched alkyl radical having 2 to 12 carbon atoms, and b is an integer from 1 to 4, and the donor is a diamine or a triamine, wherein a has a value between 0.5 and 1.5 and n has a value of 0 or 1.

3. The hydrocarbon-soluble exchange reagents according to claim 1, characterized in that the hydrocarbon-soluble exchange reagents are present as solutions having a concentration of at least 0.5 mol/kg in relation to Mg in a hydrocarbon or hydrocarbon mixture, wherein the solution contains 1 wt % or less of an ethereal solvent.

4. The hydrocarbon-soluble exchange reagents according to claim 1, characterized in that the hydrocarbons are selected from the group consisting of aromatics and aliphates.

5. The hydrocarbon-soluble exchange reagents according to claim 1, characterized in that R.sup.1 is exchanged for the aromatic residue Ar or HetAr by reacting with electron-rich halogen aromatics (HalAr), or halogen heteroaromatics (HalHetAr), wherein Hal=Cl, Br, or I, or aryl thiolates R.sup.8SAr, or hetero aryl thiolates R.sup.8SHetAr, wherein R.sup.8=alkyl, aryl, or phenyl.

6. A method for preparing the hydrocarbon-soluble exchange reagents according to claim 1, characterized in that a dialkoxy magnesium compound R.sup.2OMgOR.sup.3 is reacted with (n+1) equivalents of an alkyl lithium compound R.sup.1Li in a hydrocarbon-containing solvent or solvent mixture, wherein R.sup.1 is an alkyl group having 1 to 8 carbon atoms, n has a value of 1 or 0, and OR.sup.2 and OR.sup.3 are each independently selected from the group consisting of: a) tert-alkoxy, b) sec-alkoxy, c) primary alkoxy OCH.sub.2CHR.sup.4R.sup.5 having 3 to 12 carbon atoms, wherein the alkoxy residue has a branch at position 2 relative to the O-function and R.sup.4 and R.sup.8 independently represent alkyl radicals having 1 to 8 carbon atoms, and d) alkoxy residue, containing another alkoxy function, of the general formula O(CHR.sup.6).sub.bOR.sup.7 wherein R.sup.6=H or an alkyl radical having 1 to 6 carbon atoms, which is either linear or has a branch at position 3 or higher relative to the O-function, R.sup.7 is a linear or branched alkyl radical having 2 to 12 carbon atoms, and b is an integer from 1 to 4.

7. The method for preparing hydrocarbon-soluble exchange reagents according to claim 1, characterized in that a dialkyl magnesium compound R.sup.1MgR.sup.9 is reacted, for n=1, with one equivalent alcohol R.sup.3OH and one equivalent of a lithium alkoxide compound R.sup.2OLi, or, for n=0, with a total of two equivalents of the lithium alkoxide compounds R.sup.2OLi and/or R.sup.3OLi in a hydrocarbon-soluble solvent or solvent mixture, wherein R.sup.1 is an alkyl group having 1 to 8 carbon atoms, and OR.sup.2 and OR.sup.3 each are independently selected from the group consisting of: a) tert-alkoxy, b) sec-alkoxy, c) primary alkoxy OCH.sub.2CHR.sup.4R.sup.5, having 3 to 12 carbon atoms, wherein the alkoxy residue has a branch at position 2 relative to the O-function and R.sup.4 and R.sup.5 independently represent alkyl radicals having 1 to 8 carbon atoms, d) alkoxy residue, containing another alkoxy function, of the general formula O(CHR.sup.6).sub.bOR.sup.7 wherein R.sup.6=H or an alkyl radical having 1 to 6 carbon atoms, which is either linear or has a branch at position 3 or higher relative to the O-function, R.sup.7 is a linear or branched alkyl radical having 2 to 12 carbon atoms, and b is an integer from 1 to 4, and R.sup.9 is any alkyl group having 1 to 8 carbon atoms and R.sup.9 is either the same as, or different from, R.sup.1.

8. The method for preparing hydrocarbon-soluble exchange reagents according to claim 1, characterized in that a dialkyl magnesium compound R.sup.1MgR.sup.9 is reacted with one equivalent of a dialkoxy magnesium compound R.sup.5OMgOR.sup.3 in a hydrocarbon-containing solvent or solvent mixture, and 0.5 to 1.5 equivalents of an alkyl lithium compound R.sup.2OLi are added to this reaction mixture, wherein R.sup.1 is an alkyl group having 1 to 8 carbon atoms, and OR.sup.2 and OR.sup.3 each are independently selected from the group consisting of: a) tert-alkoxy, b) sec-alkoxy, c) primary alkoxy OCH.sub.2CHR.sup.4R.sup.5, having 3 to 12 carbon atoms, wherein the alkoxy residue has a branch at position 2 relative to the O-function and R.sup.4 and R.sup.5 independently represent alkyl radicals having 1 to 8 carbon atoms, d) alkoxy residue, containing another alkoxy function, of the general formula O(CHR.sup.6).sub.bOR.sup.7 wherein R.sup.6=H or an alkyl radical having 1 to 6 carbon atoms, which is either linear or has a branch at position 3 or higher relative to the 0-function, R.sup.7 is a linear or branched alkyl radical having 2 to 12 carbon atoms, and b is an integer from 1 to 4.

9. The method for preparing hydrocarbon-soluble exchange reagents according to claim 6, characterized in that equivalents of a donor are added to the reaction mixture from synthesis a in relation to Mg, wherein the donor is a diamine or a triamine and a has a value of 0.5 to 1.5.

10. The method for preparing hydrocarbon-soluble exchange reagents according to claim 6, characterized in that only hydrocarbon-based solvents are used.

11. A process comprising reacting the hydrocarbon-soluble exchange reagents according to claim 1 with halogenated or thiolate-functionalized aromatics or heteroaromatics of the general formulas HalAr, HalHetAr, R.sup.9SAr, or R.sup.9S-HetAr wherein R.sup.9=alkyl or aryl and reacting electrophiles with the metalated intermediates ArMgOR.sup.3.Math.LiOR.sup.2.Math.aDonor, HetArMgOR.sup.3.Math.LiOR.sup.2.Math.aDonor, Ar2Mg.Math.LiOR.sup.2.Math.LiOR.sup.3.Math.aDonor and HetAr2Mg.Math.LiOR.sup.2.Math.LiOR.sup.3.Math.aDonor for CC or CN coupling reactions or addition reactions.

12. The process of claim 11 wherein the halogenated or thiolate-functionalized aromatics or heteroaromatics have one or several functional groups selected from the group consisting of: F, Cl, Br, CN, CO.sub.2R, OR, OH, NR.sub.2, NHR, NH.sub.2, PR.sub.2, P(O)R.sub.2, CONR.sub.2, CONHR, SR, SH, CF.sub.3, NO.sub.2.

13. A process comprising reacting the hydrocarbon-soluble exchange reagents according to claim 1 in exchange reactions with electron-rich aromatics.

14. The process of claim 12 wherein the electron-rich heteroaromatics are selected from the group consisting of pyrroles, furans, thiophenes, oxazoles, isoxazoles, thiazoles, isothiazoles, imidazoles, benzimidazoles, triazoles, indazoles, and indoles.

15. The process of claim 11 wherein the halogenated aromatics or heteroaromatics are selected from the group consisting of: bromobenzene, bromotoluenes, bromoanisoles, bromo-N,N-dimethylanilines, 1-bromo-3,5-dimethoxybenzene, bromonaphthalenes, bromophenanthrenes, bromothiophenes, bromopyridines, bromobenzothiophenes, bromobenzofurans, 1,2-dibromocyclopent-1-ene, tent-butyl 2-(methylthio)piperidine-1-carboxylate, tert-butyl 2-(phenylthio)piperidine-1-carboxylate, tert-butyl 4-methyl-2-(phenylthio)piperidine-1-carboxylate, tert-butyl 2-((4-methoxyphenyl)thio)piperidine-1-carboxylate, tert-butyl 2-((4-fluorophenyl)thio)piperidine-1-carboxylate, tent-butyl 2-(phenylthio)pyrrolidine-1-carboxylate, and 2-(phenylthio)pyridine.

Description

EXAMPLE 1

Preparation of sec-BuMgOCH.SUB.2.CH(Et)Bu.Math.LiOCH.SUB.2.CH(Et)Bu from Magnesium bis(2-ethylhexanolate) and sec-BuLi

[0072] A dry Schlenk flask, which was filled with argon and equipped with a magnetic stirrer bar and a septum, was filled with Mg[OCH.sub.2CH(Et)Bu].sub.2 (0.85 M in heptane, 15.0 mL, 12.8 mmol), and the reaction mixture was cooled to 0 C. Then s-BuLi (1.21 M in hexane, 10.6 mL, 12.8 mmol) was added drop by drop. After the addition was complete, the reaction mixture was brought to 25 C. and the reaction solution was stirred for 2 hours. A slightly yellowish solution was created in the process. Then the solvent was evaporated off in a vacuum, resulting in a light yellow foam. Freshly distilled toluene (approx. 9 mL) was added under constant stirring at 0 C. The

[0073] sec-BuMgOCH.sub.2CH(Et)Bu.Math.LiOCH.sub.2CH(Et)Bu prepared in this way was iodometrically titrated at 0 C. The concentration of the resulting clear solution was equivalent to molarity of 0.80-1.3 M.

EXAMPLE 2

Preparation of sec-BuMgOCH.SUB.2.CH(Et)Bu.Math.LiOCH.SUB.2.CH(Et)Bu from dibutyl magnesium, bis(2-ethylhexanol), and sec-BuLi

[0074] A dry Schlenk flask, which was filled with argon and equipped with a magnetic stirrer bar and a septum, was filled with n-Bu.sub.2Mg (0.66 M in hexane, 15.0 mL, 9.9 mmol). Then 2-ethylhexanol (3.1 mL, 19.8 mmol) was slowly added by dripping at 0 C. under ice cooling. A gelatinous compound was created while releasing heat. This compound was then mixed at 0 C. with s-BuLi (1.21 M in hexane, 8.18 mL, 9.9 mmol). After the addition was complete, the reaction mixture was brought to 25 C. and the reaction solution was stirred for 2 hours. The gelatinous compound dissolved in the process, and a slightly yellowish solution was created. Then the solvent was evaporated off in a vacuum, resulting in a light yellow foam. Freshly distilled toluene (approx. 1 mL) was added under constant stirring at 0 C.

EXAMPLE 3

Preparation of n-BuMgOCH.SUB.2.CH(Et)Bu.Math.LiOCH.SUB.2.CH(Et)Bu

[0075] A dry Schlenk flask, filled with argon and equipped with a magnetic stirrer bar and a septum, was filled with Mg[OCH.sub.2CH(Et)Bu].sub.2 (0.85 M in heptane, 15.0 mL, 12.8 mmol), and the reaction mixture was cooled to 0 C. Then n-BuLi (2.1 M in hexane, 6.1 mL, 12.8 mmol) was added drop by drop. After the addition was complete, the reaction mixture was brought to 15 C. and the reaction solution was stirred for 2 hours. A slightly yellowish solution was created in the process. Then the solvent is evaporated off in a vacuum, resulting in a light yellow foam. Freshly distilled toluene (approx. 9 mL) was added under constant stirring at 0 C.

EXAMPLE 4

Preparation of sec-Bu.SUB.2.Mg.Math.2 LiOCH.SUB.2.CH(Et)Bu.Math.PMDTA from dibutyl magnesium, bis(2-ethylhexanol), and sec-BuLi in toluene

[0076] A dry Schlenk flask, which was filled with argon and equipped with a magnetic stirrer bar and a septum, was filled with n-Bu.sub.2Mg (0.66 M in hexane, 15.0 mL, 9.9 mmol). Then 2-ethylhexanol (3.1 mL, 19.8 mmol) was slowly added by dripping at 0 C. under ice cooling. A gelatinous compound was created while releasing heat. This compound was then mixed at 0 C. with s-BuLi (1.21 M in hexane, 16.36 mL, 19.8 mmol). After the addition was complete, the reaction mixture was brought to 25 C. and the reaction solution was stirred for 2 hours. The gelatinous compound dissolved in the process, and a slightly yellowish solution was created. Then the solvent was evaporated off in a vacuum, resulting in a light yellow foam. Freshly distilled toluene (approx. 1 mL) was added under constant stirring at 0 C.

EXAMPLE 5

Preparation of sec-Bu.SUB.2.Mg.Math.2 LiOCH.SUB.2.CH(Et)Bu from magnesium bis(2-ethylhexanolate) and sec-BuLi

[0077] A dry Schlenk flask, which was filled with argon and equipped with a magnetic stirrer bar and a septum, was filled with Mg[OCH.sub.2CH(Et)Bu].sub.2 (0.85 M in heptane, 15.0 mL, 12.8 mmol), and the reaction mixture was cooled to 0 C. Then sec-BuLi (1.21 M in hexane, 21.2 mL, 25.6 mmol) was added drop by drop. After the addition was complete, the reaction mixture was brought to 25 C. and the reaction solution was stirred for 2 hours. A slightly yellowish solution was created in the process. Then the solvent was evaporated off in a vacuum, resulting in a light yellow foam. Freshly distilled toluene (approx. 9 mL) was added under constant stirring at 0 C. The s-BuMg.sub.2.Math.2LiOCH.sub.2CH(Et)Bu was then iodometrically titrated at 0 C. The concentration of the resulting clear solution was equivalent to molarity of 0.60-0.85 M.

EXAMPLE 6

Typical Procedure for the Preparation of aryl and heteroaryl magnesium alkoxide Compounds by a bromium-magnesium Exchange

[0078] A dry flask filled with argon, equipped with a magnetic stirrer bar and a septum, is filled with the respective aryl or heteroaryl bromide (1.0 eq.) and dissolved in dry toluene (0.5 M solution) and TMEDA (1.2 eq.). The resulting solution is stirred at the respective specified temperature, and sec-BuMgOCH.sub.2CH(Et)Bu.Math.LiOCH.sub.2CH(Et)Bu (1.2 eq.) is added by dripping. The end of the bromium-magnesium exchange is verified by GC analysis of aliquots quenched with water, wherein tetradecane is used as internal standard. Then the aryl or heteroaryl magnesium alkoxide compounds are reacted with electrophiles under the specified conditions. After the reactions are complete, the reaction mixtures are quenched with saturated aqueous NH.sub.4Cl solution and extracted with EtOAc (320 mL). The combined organic phases are dried over Na.sub.2SO.sub.4, filtrated, and concentrated.

EXAMPLE 7

Typical Procedure for the Preparation of diaryl and di-heteroaryl agnesium Alkoxide Compounds by a Chlorine-Magnesium Exchange

[0079] A dry flask filled with argon, equipped with a magnetic stirrer bar and a septum, is filled with the respective aryl or heteroaryl halogen (1.0 eq.) and dissolved in dry toluene (approx. 0.5 M solution) and mixed with PMDTA (0.6 eq.). The resulting solution is stirred at the respective specified temperature, and

[0080] sec-Bu.sub.2Mg.Math.2 LiOCH.sub.2CH(Et)Bu (0.6 eq.) is added by dripping. The end of the bromium-magnesium exchange is verified by GC analysis of aliquots quenched with water, wherein tetradecane is used as internal standard. Subsequently, the aryl or heteroaryl magnesium alkoxide compounds are reacted with electrophiles under the specified conditions. After the reaction is complete, the reaction mixtures are quenched with saturated aqueous NH.sub.4Cl solution and extracted with EtOAc (320 mL). The combined organic phases are dried over Na.sub.2SO.sub.4, filtrated, and concentrated.

EXAMPLE 8

Preparation of (2,5-dimethoxyphenyl)(phenyl)methanol

[0081] According to the procedure specified in Example 7, sec-BuMg.sub.2 .2

[0082] LiOCH.sub.2CH(Et)Bu (0.76 M in toluene, 0.79 mL, 0.6 mmol, 0.6 eq.) was added by dripping to a mixture of 2-chloro-1,4-dimethoxybenzene (0.14 mL, 1.00 mmol), PMDTA (0.12 mL, 0.6 mmol), and toluene (1 mL) at 25 C. After 45 minutes, benzaldehyde (0.1 mL, 1.0 mmol, 1.2 eq.) was added and the reaction mixture was stirred for another 60 minutes at 25 C. The crude product was purified using column chromatography (silica gel, i-hexane/ethylacetate 9:1) and yielded the title compound as a colorless oil (149 mg, 0.61 mmol, 61%).

[0083] .sup.1H-NMR (400 MHz, CDCl.sub.3): /ppm=7.47-7.40 (m, 2H), 7.35 (t, J=7.4, 2H), 7.30-7.25 (m, 1H), 6.89 (d, J=2.9, 1H), 6.87-6.78 (m, 2H), 6.04 (d, J=4.1, 1H), 3.77 (d, J=3.6, 6H), 3.12 (d, J=4.8, 1H).

[0084] .sup.13C-NMR (101 MHz, CDCl.sub.3): /ppm=153.8, 151.0, 143.2, 133.2, 128.2, 127.3, 126.6, 114.1, 112.8, 111.9, 72.3, 56.0, 55.7.

[0085] MS (EI, 70 eV): m/z (%)=244 (100), 226 (11), 167 (13), 165 (15), 139 (45), 105 (30), 91 (14), 79 (12), 77 (28), 43 (37).

[0086] HRMS (EI): m/z calc. for [C.sub.15H.sub.16O.sub.3]: 244.1099; found: 244.1095.

[0087] IR (Diamond-ATR, neat):.sup.V.sup./cm.sup.1=2938, 2834, 1591, 1492, 1452, 1276, 1212, 1177, 1037, 831.

EXAMPLE 9

Typical Procedure for the Preparation of Heteroaryl Magnesium Alkoxide Compounds by a Thiolate-Magnesium Exchange:

[0088] A dry flask filled with argon, equipped with a magnetic stirrer bar and a septum, is filled with the respective thiolate-functionalized heteroarene (1.0 eq.) and dissolved in dry toluene (0.5 M solution) and mixed with approx. 3 eq. TMEDA. The resulting solution is stirred at room temperature, and sec-BuMgOCH.sub.2CH(Et)Bu.Math.LiOCH.sub.2CH(Et)Bu (3.0 eq.) is added by dripping (0.05 mL/min). The end of the thiolate-magnesium exchange is verified by GC analysis of aliquots quenched with water, wherein tetradecane is used as internal standard. Subsequently, the heteroaryl magnesium alkoxide compounds are reacted with electrophiles under the specified conditions. After the reaction is complete, the reaction mixtures are quenched with saturated aqueous NH.sub.4Cl solution and extracted with Et.sub.2O (320 mL). The combined organic phases are dried over Na.sub.2SO.sub.4, filtrated, and concentrated.

EXAMPLE 10

Preparation of tert-butyl 2-allyl-4-methylpiperidine-1-carboxylate

[0089] According to the procedure specified in Example 9, sec-BuMgOCH.sub.2CH(Et)Bu.Math.LiOCH.sub.2CH(Et)Bu (1.10 M in Toluol, 0.82 mL, 0.9 mmol 3.0 eq.) was added by dripping (0.05 mL/min) to a mixture of tent-butyl 2-(methylthio)piperidine-1-carboxylate (92 mg, 0.30 mmol), TMEDA (0.134 mL, 0.9 mmol), and toluene (0.6 mL) at 25 C. After 4 hours, allyl bromide (78 L, 0.9 mmol, 3.0 eq.) was added at 0 C., the reaction mixture was cooled to 40 C. and mixed with CuCN.Math.2 LiCl solution (1.0 M in THF, 0.09 mL, 0.09 mmol, 0.3 eq.), and then the mixture was stirred for another 14 hours at 25 C. The crude product was purified using column chromatography (silica gel, i-hexane/diethylether 95:5) and yielded the title compound as a colorless oil (59 mg, 0.25 mmol, 83%).

[0090] .sup.1H-NMR (599 MHz, CDCl.sub.3): /ppm=5.77 (ddt, J=17.2, 10.2, 7.2 Hz, 1H), 5.08-4.97 (m, 2H), 3.85 (tt, J=8.3, 6.3 Hz, 1H), 3.73 (ddd, J=13.9, 7.3, 3.2 Hz, 1H), 3.01 (ddd, J=13.9, 10.3, 5.9 Hz, 1H), 2.40 (dddt, J=14.2, 7.1, 5.9, 1.4 Hz, 1H), 2.24 (dtt, J=13.5, 7.6, 1.1 Hz, 1H), 1.87 (ddtd, J=13.3, 10.3, 7.2, 1.2 Hz, 1H), 1.73-1.68 (m, 1H), 1.68-1.62 (m, 1H), 1.45 (s, 8H), 1.20-1.12 (m, 1H), 1.12-1.06 (m, 1H), 0.98 (d, J=6.8 Hz, 3H).

[0091] .sup.13C-NMR (101 MHz, CDCl.sub.3): /ppm=155.4, 135.4, 116.7, 79.0, 53.0, 39.0, 37.4, 34.9, 31.1, 28.4, 26.1, 21.5.

[0092] MS (EI, 70 eV): m/z (%)=166 (3), 143 (8), 142 (100), 98 (46), 57 (3), 56 (5).

[0093] HRMS (EI): m/z calc. for [C.sub.10H.sub.16ON]: 166.1232; found: 166.1225.

[0094] IR (Diamond-ATR, neat):.sup.V.sup./cm.sup.1=2976, 2928, 2872, 1688, 1642, 1478, 1456, 1408, 1392, 1364, 1350, 1332, 1304, 1278, 1246, 1178, 1148, 1094, 1070, 992, 912, 866, 770.

EXAMPLE 11

Typical Procedure for the Preparation of Alkinyl Magnesium Alkoxide Compounds by Deprotonation

[0095] A dry flask filled with argon, equipped with a magnetic stirrer bar and a septum, is filled with the respective alkine (1.0 eq.) and dissolved in dry toluene (0.5 M solution) and TMEDA (1.2 eq.). The resulting solution is stirred at the respective specified temperature, and sec-BuMgOCH.sub.2CH(Et)Bu.Math.LiOCH.sub.2CH(Et)Bu (1.2 eq.) is added by dripping. The end of the deprotonation is verified by GC analysis of aliquots quenched with water, wherein tetradecane is used as internal standard. Then the alkinyl magnesium alkoxide compounds are reacted with electrophiles under the specified conditions (see diagram 4). After the reaction is complete, the reaction mixtures are quenched with saturated aqueous NH.sub.4Cl solution and extracted with EtOAc (320 mL). The combined organic phases are dried over Na.sub.2SO.sub.4, filtrated, and concentrated.

EXAMPLE 12

Preparation of 4-iodoanisole

[0096] According to the procedure specified in Example 7, sec-BuMgOCH.sub.2CH(Et)Bu.Math.LiOCH.sub.2CH(Et)Bu (0.80 M in toluene, 0.75 mL, 0.6 mmol, 1.2 eq.) was added by dripping to a mixture of 4-bromoanisole (0.06 mL, 0.50 mmol), TMEDA (0.09 mL, 0.6 mmol), and toluene (1 mL) at 25 C. After 15 minutes, iodine (152 mg in 1 mL THF, 0.6 mmol, 1.2 eq.) was added and the reaction mixture was stirred for another 30 minutes at 25 C. The crude product was purified using column chromatography (silica gel, i-hexane/ethylacetate 9:1) and yielded the title compound as a white solid substance (81 mg, 0.35 mmol, 70%).

[0097] .sup.1H-NMR (400 MHz, CDCl.sub.3): /ppm=7.63-7.49 (d, 2H), 6.76-6.61 (d, 2H), 3.78 (s, 3H).

[0098] .sup.13C-NMR (101 MHz, CDCl.sub.3): /ppm=159.6, 138.3, 116.5, 82.8, 55.5.

[0099] MS (EI, 70 eV): m/z (%)=234 (100), 191 (15), 92 (64).

[0100] HRMS (EI): m/z calc. for [C.sub.7H.sub.7IO]: 233.9542; found: 233.9540.

[0101] IR (Diamond-ATR, neat):.sup.V.sup./cm.sup.1=3006, 2966, 2938, 2837, 1586, 1569, 1486, 1456, 1444, 1436, 1397, 1287, 1248, 1179, 1175, 1102, 1028, 999, 833, 829, 813. 8