Expedient Access to Underexplored Chemical Space: Deoxygenative C(sp)-C(sp) Cross-Coupling

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2023 Mar 28

PMID 36975797

Authors

William L Lyon

David W C MacMillan

Affiliations

Soon will be listed here.

Abstract

Alcohols are commercially abundant and structurally diverse reservoirs of sp-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)-C(sp) 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.

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