Metal‐Free Reductive Aldol Reactions

Abstract

The reductive aldol reaction (RAR) is an important carbon-carbon bond-forming reaction. Several methods have been developed with the RAR as the key step to access complex molecular frameworks. An overview of the literature pertaining to the metal-free reductive aldol chemistry is presented. The RARs facilitated by boranes, phosphine oxides, and phosphines is deliberated in a comprehensive manner. The scope, limitations, mechanistic insights and applications of these methods are also discussed.

Conceptual advances in nucleophilic organophosphine-promoted transformations

“…The aldol reaction is one of the most well-explored C–C bond-forming reactions involving two carbonyl compounds as reactants. 26 One behaves as the pool of latent enolate, and the other serves as an electron sink, forming β-hydroxy carbonyls, Scheme 7(a). Over several decades, the synthetic utility of the aldol reaction has been investigated in constructing many structurally challenging molecules.…”

Intramolecular Phosphine-Promoted Knoevenagel Based Redox-Reaction

“…Phosphine Lewis bases that catalyze internal redox transformations are known in literature [ 24 ]. However, only two examples of phosphine-promoted reductive aldol reactions have been published [ 25 ]. Recently a homogenous phosphine-promoted reductive aldol reaction of activated α,β -unsaturated carbonyls with aldehydes was reported by Gu et al An external triphenylphosphine molecule was applied to perform a phospha-Michael addition leading to a zwitterionic enolate, followed by P–O bond formation and C–P bond cleavage to give reduced aldol compounds [ 26 ].…”