Asymmetric synthesis of α-methoxyarylacetic acid derivatives

Stereoselective synthesis of a series of 2-aryl-2-methoxyethanols was achieved from inexpensive chiral pool tartaric acid employing a diastereoselective reduction of a symmetrical 1,4-diaryldiketone as the key step. 2-Aryl-2-methoxyethanols were enantioselectively prepared in 80–90% yield

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(−)-(1R,2R,3R,4R)-1,4-Dimethoxy-1,4-diphenylbutane-2,3-diolC18H22O4[α]D = −144 (c 1.0, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (1R,2R,3R,4R)

(−)-(1R,2R,3R,4R)-1,4-Dimethoxy-1,4-di-(4-methylphenyl)-butane-2,3-diolC20H26O4[α]D = −213 (c 0.3, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (1R,2R,3R,4R)

(−)-(1R,2R,3R,4R)-1,4-Dimethoxy-1,4-bis(3,4-dimethylphenyl)butane-2,3-diolC22H30O4[α]D = −152.8 (c 0.7, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (1R,2R,3R,4R)

(−)-(1R,2R,3R,4R)-1,4-Dimethoxy-1,4-bis(4-methoxyphenyl)butane-2,3-diolC20H26O6[α]D = −133.3 (c 0.3, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (1R,2R,3R,4R)

(−)-(R)-2-Methoxy-2-phenylacetic acidC9H10O3[α]D = −141.8 (c 0.13, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: R

(−)-(R)-2-Methoxy-2-phenylethanolC9H12O2[α]D = −146.0(c 0.13, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: R

(−)-(R)-2-Methoxy-2-(4-methoxyphenyl)ethanolC10H14O3[α]D = −110.0 (c 0.5, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: R

(−)-(R)-2-Methoxy-2-(4-methylphenyl)ethanolC10H14O2[α]D = −230.0 (c 0.5, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: R

(−)-(R)-2-Methoxy-2-(3,4-dimethylphenyl)ethanolC11H16O2[α]D = −96.7 (c 1.2, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: R