A Straightforward Synthesis of Trideuterated α-Terpinene for Mechanistic Studies

Abstract

Regiospecifically trideuterated (2,6,6-2H3)-α-terpinene was prepared in six steps and with a deuterium incorporation of >99 % in 24 % yield from 1,4-cyclohexanedione monoethylene ketal. The synthetic procedure involved twofold cross-coupling reactions of alkylcuprates (lithium dimethylcuprate and chloromagnesium cyano(isopropyl)cuprate, respectively) with enol triflates to introduce the alkyl substituents on the 1,3-cyclohexadiene backbone. By changing the alkylcuprates, the synthetic approach could serve as a prototype for the synthesis of various 1,4-dialkyl-substituted 1,3-cyclohexadiene derivatives, which could be deuterium-labeled as well, for example for mechanistic studies.