Chemoenzymatic synthesis of optically active γ-alkyl-γ-butenolides

rac-Hept-1-en-3-ol 4 was subjected to an enantioselective esterification in the presence of Novozyme 435 and vinyl crotonate as the acyl donor to give (3S)-oct-1-en-3-yl crotonate 7 in >99% ee and (3R)-alcohol 4 in 99% ee. The E-value of this enzymatic reaction was found to be >1000. The (S)-crotonic ester 7 was converted by ring-closing metathesis (RCM) using Grubbs’ catalyst to give (S)-oct-2-en-4-olide 1 in 96% yield while keeping the high enantiomeric excess.

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(S)-Oct-2-en-4-olideC8H12O2[α]D25=+100.4 (c 1.01, CHCl3)Source of chirality: (3S)-hept-1-en-3-yl crotonate

(S)-Hept-2-en-4-olideC7H10O2[α]D25=+110.0 (c 1.16, CHCl3)Source of chirality: (3S)-hex-1-en-3-yl crotonate

(S)-Non-2-en-4-olideC9H14O2[α]D25=+94.0 (c 1.05, CHCl3)Source of chirality: (3S)-oct-1-en-3-yl crotonate

(S)-Dec-2-en-4-olideC10H16O2[α]D25=+89.4 (c 1.01, CHCl3)Source of chirality: (3S)-non-1-en-3-yl crotonate

(3S)-Hept-1-en-3-yl crotonateC11H18O2Ee >99%[α]D25=+6.9 (c 1.16, CHCl3)Source of chirality: resolution by lipase-catalyzed esterification