Regiospecific Synthesis of Trimethylsilyl Enol Ethers

Abstract

Continuing interest in the use of trimethylsilyl enol ethers 1 as synthetic intermediates,¹ has prompted efforts toward developing efficient, regiospecific methods for the preparation of these versatile compounds. In general, silylation of enolate anions with chlorotrimethyl silane (CTMS) has proven to be the procedure most widely used.^2,3,4 In the case of unsymmetrical ketones such as 2, (Table 1) the use of strong base (LDA) (entry 1) allows kinetic deprotonation, and hence, the highly regioselective production of 1a′ upon CTMS quenching. However, attempts to prepare 1a by resorting to conditions which equilibrate the enolate prior to CTMS quenching affords mixtures of 1a′ and 1a (entries 2–4). Further, equilibration of 1a′ and 1a does not give synthetically useful mixtures⁵.