Acylation of electrophilic bicyclo[1.1.0]butanes via Co/Ni-catalyzed reductive cross-coupling

Abstract

Cyclobutane scaffold is appreciated in medicinal chemistry for its strained, well-defined three-dimensional structure. Consequently, methods for the synthesis of cyclobutyl derivatives have become highly desired, particularly those offering access to compounds with new patterns of substituents. Herein, an acylation of electrophilic strained molecules at the bridgehead carbon with [Formula: see text]-acyl-glutarimides is reported. For this, the polarity-reversal strategy based on cobalt catalysis that enables the generation of cyclobutyl radicals in a strain release event was harnessed. These nucleophilic species, in the presence of a Ni-complex, couple with [Formula: see text]-acyl-glutarimides to give cyclobutyl ketones in decent yields.