Catalytic enantioselective addition of methyltriisopropoxititanium to aldehydes

An efficient catalyst for the enantioselective synthesis of chiral methyl carbinols from aldehydes is presented. The system uses methyltriisopropoxytitanium as a nucleophile and a readily available binaphthyl derivative as a chiral ligand. The enantioselective methylation of both aromatic and aliphatic aldehydes proceeds with good yields and high enantioselectivities under mild conditions.

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(R)-1-PhenylethanolC8H10OEe = 96%[α]D24 = +47 (c 0.7, CHCl3)Source of chirality: (Ra,S)-Ph-BINMOLAbsolute configuration: (R)

(R)-1-(2-Methoxyphenyl)ethanolC9H12O2Ee = 56%[α]D24 = +33 (c 0.3, CHCl3)Source of chirality: (Ra,S)-Ph-BINMOLAbsolute configuration: (R)

(R)-1-(3-Methoxyphenyl)ethanolC9H12O2Ee = 99.5%[α]D24 = +28 (c 1, CHCl3)Source of chirality: (Ra,S)-Ph-BINMOLAbsolute configuration: (R)

(R)-1-(4-Methylphenyl)ethanolC9H12OEe = 93%[α]D25 = +39.4 (c 0.7, CHCl3)Source of chirality: (Ra,S)-Ph-BINMOLAbsolute configuration: (R)

(R)-1-(4-Bromophenyl)ethanolC8H9BrOEe = 97%[α]D25 = +28 (c 0.4, CHCl3)Source of chirality: (Ra,S)-Ph-BINMOLAbsolute configuration: (R)

(R)-1-[4-(Trifluoromethyl)phenyl]ethanolC9H9F3OEe = 95%[α]D25 = +28.9 (c 0.9, CHCl3)Source of chirality: (Ra,S)-Ph-BINMOLAbsolute configuration: (R)

(R)-4-(1-Hydroxyethyl)benzonitrileC9H9NOEe = 96%[α]D25 = +35.3 (c 0.9, CHCl3)Source of chirality: (Ra,S)-Ph-BINMOLAbsolute configuration: (R)

(R)-1-(Naphthalen-2-yl)ethanolC12H12OEe = 84%[α]D24 = +31 (c 0.4, CHCl3)Source of chirality: (Ra,S)-Ph-BINMOLAbsolute configuration: (R)

(R)-1-(Thiophen-2-yl)ethanolC6H8SOEe = 94%[α]D24 = +12.5 (c 0.8, CHCl3)Source of chirality: (Ra,S)-Ph-BINMOLAbsolute configuration: (R)

(R,E)-4-Phenylbut-3-en-2-olC10H12OEe = 82%[α]D24 = +35 (c 0.6, CHCl3)Source of chirality: (Ra,S)-Py-BINMOLAbsolute configuration: (R)

(R)-1-Phenylpropan-2-olC9H12OEe = 85%[α]D25 = −35.4 (c 0.7, CHCl3)Source of chirality: (Ra,S)-Py-BINMOLAbsolute configuration: (R)

(R)-Nonan-2-yl acetateC11H22O2Ee = 90%[α]D25 = −5.6 (c 0.9, CHCl3)Source of chirality: (Ra,S)-Py-BINMOLAbsolute configuration: (R)