Direct α-Tertiary Alkylations of Ketones in a Combined Copper-Organocatalyst System

Herein, we report an efficient method for the tertiary alkylation of a ketone by using an alpha-bromocarbonyl compound as the tertiary alkyl source in a combined Cu-organocatalyst system. This dual catalyst system enables the addition of a tertiary alkyl radical to an enamine. Mechanistic studies revealed that the catalytically generated enamine is a key intermediate in the catalytic cycle. The developed method can be used to synthesize substituted 1,4-dicarbonyl compounds containing quaternary carbons bearing various alkyl chains.

Automated summary

This study developed an efficient method for the tertiary alkylation of a ketone using an alpha-bromocarbonyl compound as the tertiary alkyl source in a combined Cu-organocatalyst system, allowing the addition of a tertiary alkyl radical to an enamine. Mechanistic studies indicated that the catalytically generated enamine plays a key role in the catalytic cycle, enabling the synthesis of substituted 1,4-dicarbonyl compounds containing quaternary carbons with various alkyl chains.