α -(Aminomethyl)acrylates as acceptors in radical – polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

Abstract
We demonstrate that α-(aminomethyl)acrylates are suitable acceptors for 1,4-additions of dialkylzincs in aerobic conditions. The air-promoted radical–polar crossover process involves the 1,4-addition of an alkyl radical followed by homolytic substitution at the zinc atom of dialkylzinc. Coordination of the nitrogen atom to zinc enables this SH2 process which represents a rare example of alkylzinc-group transfer to a tertiary α-carbonyl radical. The zinc enolate thus formed readily undergoes β-fragmentation unless it is trapped by electrophiles in situ. Enolates of substrates having free N–H bonds undergo protodemetalation to provide ultimately the 1,4-addition adduct. In the presence of carbonyl acceptors, aldol condensation occurs providing overall a tandem 1,4-addition–aldol process. When a tert-butanesulfinyl moiety is present on the nitrogen atom, these electrophilic substitution reactions occur with good levels of chiral induction, paving the way to enantioenriched β2-amino acids and β2,2-amino acids.

Beilstein J. Org. Chem. 2023, 19, 1443–1451. doi:10.3762/bjoc.19.103

Source: Beilstein Journal of Organic Chemistry - September 21, 2023 Category: Chemistry Authors: Beilstein Journal of Organic Chemistry - Syndicated Feeds Tags: β -amino acids tandem reactions radical – polar crossover tert-butanesulfinamide zinc radical transfer Full Research Paper Source Type: research