The Cyclopropane Ring as a Reporter of Radical Leaving-Group Reactivity for Ni-Catalyzed C(sp <sup>3</sup> )–O Arylation
L. Reginald Mills, John J. Monteith, Gabriel dos Passos Gomes, Alán Aspuru‐Guzik, Sophie A. L. Rousseaux
Abstract
The ability to understand and predict reactivity is essential for the development of new reactions. In the context of Ni-catalyzed C(sp3)–O functionalization, we have developed a unique strategy employing activated cyclopropanols to aid the design and optimization of a redox-active leaving group for C(sp3)–O arylation. In this chemistry, the cyclopropane ring acts as a reporter of leaving-group reactivity, since the ring-opened product is obtained under polar (2e) conditions, and the ring-closed product is obtained under radical (1e) conditions. Mechanistic studies demonstrate that the optimal leaving group is redox-active and are consistent with a Ni(I)/Ni(III) catalytic cycle. The optimized reaction conditions are also used to synthesize a number of arylcyclopropanes, which are valuable pharmaceutical motifs.