A New General Synthesis of Isoprenoid Chains Employing the Reaction of Dialkylcuprates with β-Acetoxy α,β-Unsaturated Esters

Abstract

We recently reported the reaction of lithium dialkycuprates with β-acetoxy α,β-unsaturated esters which provides a stereoselective synthesis of the corresponding alkyl substituted α,β-unsaturated esters. We now

report the application of this new reaction in a stepwise general synthesis of isoprenoid chains. The four carbon chain of the isoprene unit is derived from methyl acetoacetate while the isoprene side chain is introduced via lithium dialkylcuprates. Reaction of an alkyl halide with the dianion of methyl acetoacetate gives the γ-alkylated β-keto ester and accomplishes a four carbon chain extension of the alkyl halide.²,³ The β-keto ester can then be converted stereoselectively to the Z-isomer of the β-acetoxy α,β-unsaturated ester by reaction with isopropenyl acetate.⁴ Reaction of the β-acetoxy α,β-unsaturated ester with a lithium dialkylcuprate stereo-selectively replaces the acetoxy group with an alkyl group and accomplishes the introduction of the side chain of the isoprene unit. The resulting α,β-unsaturated ester can be converted by successive metal hydride reduction and PBr₃ bromination to an allylic bromide which can serve as the

starting point for the introduction of additional isoprene units.