Preparation of Optically Active δ-Tri- and δ-Tetradecalactones by a Combination of Novozym 435-catalyzed Enantioselective Methanolysis and Amidation.

A combination of Novozym 435-catalyzed methanolysis and amidation using racemic N-methyl-5-acetoxytridecan- and tetradecanamides as a substrate proceeded in good enantioselectivity to afford the corresponding (R)-N-methyl-5-acetoxyalkanamides, (S)-N-methyl-5-hydroxyalkanamides, and (S)-N-cyclohexyl-5-hydroxyalkanamides. Both enantiomers of δ-tri- and δ-tetradecalactones were synthesized in over 90% enantiomeric excesses from the corresponding (R)- or (S)-alkanamides. Addition of cyclohexylamine to Novozym 435-catalyzed methanolysis shortened 24-hour reaction time to reach about 50% conversion. Enantiomers of optically active δ-tri- and δ-tetradecalactones had different odors and thresholds.