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. 2023 Apr 12;145(14):7736-7742.
doi: 10.1021/jacs.3c01488. Epub 2023 Mar 28.

Expedient Access to Underexplored Chemical Space: Deoxygenative C(sp3)-C(sp3) Cross-Coupling

William L Lyon  1 , David W C MacMillan  1
Affiliations

Expedient Access to Underexplored Chemical Space: Deoxygenative C(sp3)-C(sp3) Cross-Coupling

William L Lyon et al. J Am Chem Soc. .

Abstract

Alcohols are commercially abundant and structurally diverse reservoirs of sp3-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(sp3)-C(sp3) 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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Conflict of interest statement

The authors declare the following competing financial interest(s): D.W.C.M. declares a competing financial interest with respect to the integrated photoreactor.

Figures

Figure 1.
Figure 1.
Cross-coupling of alcohols and alkyl bromides.
Figure 2.
Figure 2.
Proposed mechanism.
See this image and copyright information in PMC

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