Oxidative Single-Step Umpolung α-Alkylation of Carbonyl Compounds

Orel Svetlana Shneider, Chemistry, Technion, Haifa, Israel

A novel alkylative reaction of 1,3-dicarbonyl compounds or ketone enolates has been designed, developed and studied.¹ The reaction entails oxidative umpolung reaction mediated by the hypervalent iodine oxidant, Koser’s reagent, at the α position of the carbonyl compound, while employing dialkylzinc reagents as the alkyl source.

The reaction was found to be applicable to a wide range of carbonyl compounds including 1,3- dicarbonyl compounds and ketones, as well as capable of forming quaternary carbon centres. The alkylated carbonyl products were formed in good to excellent up to 93% yields. Extensive mechanistic studies were performed, in order to examine possible carbene, radical, and ionic pathways. Based on meticulous product analysis, NMR studies, and cross-over experiments, an ionic mechanism was deduced.

¹ O. Svetlana Shneider, Evgeni Pisarevsky, Peter Fristrup and Alex M. Szpilman, Org. Lett., 2015, In press. DOI: 10.1021/ol503384c