Catalytic Asymmetric Oxidative Enamine Transformations

Abstract

Enamine catalysis is a prevalent strategy for the functionalization of aldehydes/ketones with electrophiles. Recently, the advent and development of oxidative enamine catalysis have allowed for the coupling of enamines with readily available nucleophiles under oxidative conditions, significantly expanding the domain of typical enamine catalysis. In this perspective, we summarize the recent advances in asymmetric oxidative enamine catalysis. On the basis of the oxidative strategy, these could be classified as (1) oxidation of nucleophile, (2) oxidation of enamine via single-electron transfer (SOMO catalysis), and (3) oxidation of enamine to α,β-unsaturated iminium ion, i.e. oxidative iminium catalysis. These strategies have enabled efficient oxidative functionalizations of aldehydes/ketones with various O-, N-, and C-centered nucleophiles in a highly stereocontrolled manner.

Umpolung Strategy for α‐Functionalization of Aldehydes for the Addition of Thiols and other Nucleophiles

“…In particular, umpolung of enamines has broadened the scope of conventional enamine catalysis. [1] Based on asingle-electron transfer oxidation, MacMillan et al introduced the concept of SOMO activation, where an enamine is oxidized in situ generating ar adical-cation intermediate (Scheme 1c). This activation principle has provided attractive strategies for a-alkylations, a-allylations, a-vinylations, a-alkynylations,a nd a-arylations of aldehydes.…”

Enantioselective aerobic oxidative cross-dehydrogenative coupling of glycine derivatives with ketones and aldehydes via cooperative photoredox catalysis and organocatalysis

“…Within the same time frame, condensation of 2a with chiral amine A should form a nucleophilic enamine intermediate III, which would then intercept the electrophile 4a to enantioselectively forge the new C-C bond. 20 Finally, subsequent hydrolysis of iminium intermediate IV would regenerate the organocatalyst A while providing the enantioenriched coupling product 3aa.…”

Recent Advances in Asymmetric Catalytic Electrosynthesis

“…Asymmetric C-H functionalization of α-positions in carbonyl compounds through enamine intermediates is a well-explored topic in organocatalysis, often employing proline-derived catalysts [26]. In an electrochemical setting, Jang and co-workers reported on α-oxyamination of aldehydes in the presence of the prolinol derivative (S)-α,α-diphenyl-2-pyrrolidine methanol trimethylsilyl ether in catalytic amounts using platinum electrodes under constant current in an undivided cell (Scheme 1a) [27].…”