Nickel-Catalyzed C(sp3)–H Arylation for the trans-Selective Synthesis of Sterically Congested Cyclopropanes and Other Cycloalkanes

Abstract

Cyclopropanes with a gem-substitution pattern are of significant structural importance, with key applications in the fields of drug design and agrochemistry. However, despite substantial progress in 4d- and 5d-metal-catalyzed C–H activation of cyclic alkanes, direct functionalization of gem-dimethyl substituted cyclopropanes remained an unmet challenge. In this paper, we set out a preliminary general strategy to address this challenge. Not only abundant and inexpensive Ni-catalyst can be used, but also the uncommon trans-selectivity can be attained under the optimized reaction conditions. This direct arylation reaction demonstrates a broad substrate scope in terms of aryl-iodide coupling partner. In addition to this, it can be directly applied to the functionalization of other cyclic alkanes, including adamantyl cores, which are notoriously challenging to process. The experimental mechanistic studies, in combination with DFT calculations, provide a rational explanation for the mechanism of this transformation and the uncommon trans-selectivity.