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8.1.17 Product Subclass 17: α-Lithio Aldehydes, α-Lithio Ketones, and Related Compounds

DOI: 10.1055/sos-SD-008-00312

Caine, D.Science of Synthesis, (20068499.

General Introduction

The structural designation for the class of lithium compounds named in the title is a formal one. It originates from the observation that, upon treatment with strong lithium amide and other lithium bases, aldehydes and ketones (as well as the corresponding imine derivatives) yield organolithium intermediates (LiCCXY), which react with many electrophilic reagents (e.g., alkylating agents and carbonyl compounds) to give the corresponding α-substituted products. These reagents have therefore been classified as d2-synthons.[‌1‌] However, the conjugate bases of aldehydes and ketones and their imine derivatives are now almost universally referred to as lithium enolates and lithium azaenolates, respectively, and this later terminology will be used throughout this review. Lithium α-enolates of aldehydes are formally included in this subclass. However, it should be pointed out that although such intermediates can be generated in appropriate aprotic solvents, they prove to be essentially useless synthetic intermediates. This is because the high electrophilicity of the carbonyl group of aldehydes makes them prone to participate in self-condensation and other reactions involving the attack of nucleophiles at the carbonyl carbon atom. Therefore, the use of lithium enolates of aldehydes as nucleophiles will not be included here. Fortunately, as will be described below, lithium azaenolates of imines and hydrazones of aldehydes have widespread use in organic synthesis because of their lower reactivity and their ability to function as latent aldehyde enolates.

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