Synthesis of 4‐Hydroxy‐5‐methyl‐ and 4‐Hydroxy‐6‐methylcyclohexenones by Pd II ‐Catalyzed Oxidation and Lipase‐Catalyzed Hydrolysis

A short route for the syntheses of methyl‐substituted hydroxycyclohexenones, which are building blocks for various natural products, is presented. Both oxygen atoms were introduced as acetates by a palladium(II)‐catalyzed 1,4‐addition to a 1,3‐diene. The distinction between the two acetoxy groups was achieved by regioselective monohydrolysis with lipase from Candida rugosa , which gave 1‐acetoxy‐4‐hydroxy‐5‐methylcyclohexene and its 6‐methyl regioisomer as a separable mixture. The target compounds 4‐hydroxy‐5‐methylcyclohex‐2‐enone and 4‐hydroxy‐6‐methylcyclohex‐2‐enone could then be obtained as diastereomeric mixtures in good overall yields and with moderate enantiomeric excesses (31–67 %).