Photoinduced nickel-catalyzed reductive acyl cross-coupling: facile access to all carbon quaternary aliphatic ketones

All carbon quaternary aliphatic ketones are difficult to synthesize via the traditional organometallic approach. The recently developed reductive cross-coupling strategy provides a facile access to alpha-tertiary ketones with coupling of either tertiary acyl electrophiles or tertiary alkyl radicals. However, due to the large steric hindrance effect, both tertiary acyl and alkyl reagents are largely restricted to highly strained ring systems. Herein, we develop a photoinduced nickel-catalyzed reductive acyl-coupling with two different carboxylic acid esters to synthesize sterically bulky alpha-tertiary ketones in the absence of an exogenous photocatalyst and a metal reductant. Various unstrained tertiary acyl electrophiles derived from native tertiary carboxylic acids can couple with 1 degrees, 2 degrees, and 3 degrees alkyl radicals to afford all carbon quaternary aliphatic ketones, including alpha-tertiary amino ketones under mild conditions, structures which have been previously difficult to access or not yet been explored in literature.

Automated summary

A photoinduced nickel-catalyzed reductive acyl-coupling reaction has been developed, enabling the synthesis of sterically bulky alpha-tertiary ketones. The reaction does not require an exogenous photocatalyst or a metal reductant, and various unstrained tertiary acyl electrophiles can be coupled with alkyl radicals under mild conditions, leading to the formation of all carbon quaternary aliphatic ketones, including alpha-tertiary amino ketones.