Synthesis of precursors of phomactins using [2,3]-Wittig rearrangements

o-Toluic acid has been converted into methyl (8RS,9SR)-7-(bromomethyl)-8,9-dimethyl-1,4-dioxaspiro[4.5]dec-6-ene-8-carboxylate, the stereochemical defining step being a conjugate addition of lithium dimethylcuprate to a cyclohexadienone prepared using a Birch reduction followed by an allylic oxidation. Displacement of the bromide with various propargylic alcohols followed by reduction of the ester and protection of the primary alcohol so formed then gave a series of propargyl cyclohexenylmethyl ethers. [2,3]-Wittig rearrangements of these and related propargylic ethers were studied as an approach to precursors of phomactins. The rearrangements were found to proceed by regioselective deprotonation of the propargylic side-chain to give substituted methylenecyclohexanes but mixtures of stereoisomers were obtained. Aspects of the chemistry of the Wittig rearrangement products were investigated including epoxidation, oxidation of the side-chain hydroxyl groups to give 2-ynones and reactions of the 2-ynones with lithium dimethylcuprate. The propargyl side-chain of a Wittig rearrangement precursor was elaborated to prepare an intermediate, which was fully functionalised for incorporation into a phomactin. © 2009 Elsevier Ltd. All rights reserved.