Expedient Access to Underexplored Chemical Space: Deoxygenative C(sp<sup>3</sup>)–C(sp<sup>3</sup>) Cross-Coupling
William L. Lyon, David W. C. MacMillan
Abstract
Alcohols are commercially abundant and structurally diverse reservoirs of sp 3 -hybridized chemical space. However, the direct utilization of alcohols in C–C bond-forming cross-couplings remains underexplored. Herein we report an N-heterocyclic carbene (NHC)-mediated deoxygenative alkylation of alcohols and alkyl bromides via nickel–metallaphotoredox catalysis. This C(sp 3 )–C(sp 3 ) cross-coupling exhibits a broad scope and is capable of forming bonds between two secondary carbon centers, a longstanding challenge in the field. Highly strained three-dimensional systems such as spirocycles, bicycles, and fused rings were excellent substrates, enabling the synthesis of new molecular frameworks. Linkages between pharmacophoric saturated ring systems were readily forged, representing a three-dimensional alternative to traditional biaryl formation. The utility of this cross-coupling technology is highlighted with the expedited synthesis of bioactive molecules.