Reduction with lithium dialkylamides

Abstract

A reaction in which a lithium dialkylamide transfers a hydride ion to another species (Fig. l(c)) and thus functions as a reducing agent is an easy-to-imagine analogy to the Meerwein-Ponndorf-Verley reduction [l] (Fig. l(b), where E+ is a ketone). Similar hydride transfer processes (Fig. l(a)), involving Grignard reagents and other organometallics, are also well known [2]. Organometallic compounds and lithium amides can also transfer an electron to another species and thus initiate a single-electron transfer (SET) pathway leading to reduction [3,4]. Cases of reduction with lithium amides proceeding via both SET and hydride transfer mechanisms were, in fact, observed in the past: however, they did not attract a lot of attention from organic chemists. Lithium amides are amongst the most often used reagents in synthetic laboratories, and all practitioners of enolate chemistry should be aware of these reagents’ potential for reducing organic compounds. Lithium dialkylamide bases were first synthesized about 60 years ago [5] and were subsequently developed as reagents for enolization of carbonyl compounds [6,7]. The most popular of these amides is lithium diisopropylamide (LDA), which is truly an indispensable reagent in modern organic synthesis [6-91. The importance of lithium amides is underscored by extensive literature spanning topics as diverse as their formation [9], selective enolization of carbonyl compounds [lo], theoretical and experimental studies of their structure in the gas phase and in solution [ill,