Enantioselective synthesis of (R)- and (S)-curcumene and curcuphenol: an efficient chemoenzymatic route

An efficient enantioselective synthesis of curcumene and curcuphenol is described. The key intermediates, substituted butanoates 7a and 7b and their acids 8a and 8b are obtained in high enantiopurity (>99% ee) by a lipase-catalyzed kinetic resolution process. The enantiopure intermediates thus obtained were utilized for the total synthesis of the target compounds.

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(3R)-Ethyl 3-(4-methylphenyl)butanoateC13H18O2[α]D25=-26.2 (c 3.5, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(3R)-Ethyl 3-(2-methoxy-4-methylphenyl)butanoateC14H20O3[α]D25=-2.7 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(3S)-3-(4-Methylphenyl)butanoic acidC11H14O2[α]D25=+34.2 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(3S)-3-(2-Methoxy-4-methylphenyl)butanoic acidC12H16O3[α]D25=+16.2 (c 2.5, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(3S)-3-(4-Methylphenyl)-1-butanolC11H16O[α]D25=+30.1 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(3S)-3-(2-Methoxy-4-methylphenyl)-1-butanolC12H18O2[α]D25=+21.6 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(3S)-3-(4-Methylphenyl)butyl 4-methyl-1-benzenesulfonateC18H22O3S[α]D25=+37.7 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(3S)-3-(2-Methoxy-4-methylphenyl)butyl 4-methyl-l-benzenesulfonateC19H24O4S[α]D25=+14.2 (c 3.6, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(6S)-2-Methyl-6-(4-methylphenyl)-2-hepteneC15H22[α]D25=+42.7 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (6S)

(6S)-6-(2-Methoxy-4-methylphenyl)-2-methyl-2-hepteneC16H24O[α]D25=+7.1 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (6S)

2-[(1S)-1,5-Dimethyl-4-hexenyl]-5-methylphenolC15H22O[α]D25=+23.5 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1S)