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

Abstract

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 %).

Diversity-oriented synthesis of Lycopodium alkaloids inspired by the hidden functional group pairing pattern

“…The enone 7 and aldehyde 8 were synthesized from known compounds in one and two steps, respectively (see Supplementary Methods for details). Notably, as emphasized by Bräse and co-workers 48 , the chiral non-racemic enone 7 may serve as a key building block for many natural products. However, its preparation was quite difficult.…”

A Stereoselective Approach to Functionalized Cyclohexenones

“…[11] ). Chemical shifts are expressed in parts per million (ppm, δ) downfield from tetramethylsilane (TMS) and are referenced to the residual solvent peaks.…”

“…[11] and Supporting Information). in absolute THF (2 mL) under argon were added 1,4-adduct 8 (40.0 mg, 235 μmol, 1.00 equiv.)…”

“…in absolute THF (2 mL) under argon were added 1,4-adduct 8 (40.0 mg, 235 μmol, 1.00 equiv.) [11] ). Then, BH 3 ·THF (1 m in THF, 470 μL, 470 μmol, 2.00 equiv.)…”

“…For example, our group recently pre- [ sented a flexible pathway in only six steps towards both cyclohexenones 1 and 2. [11] Earlier, an enantioselective seven-step synthesis of the trans isomer of 2 was published. [12] Piers and co-workers described an eight-step synthesis towards racemic PMB-protected cis-2 (PMB = paramethoxybenzyl).…”