Unknown

Dataset Information

0

Metallaphotoredox-enabled deoxygenative arylation of alcohols.


ABSTRACT: Metal-catalysed cross-couplings are a mainstay of organic synthesis and are widely used for the formation of C-C bonds, particularly in the production of unsaturated scaffolds1. However, alkyl cross-couplings using native sp3-hybridized functional groups such as alcohols remain relatively underdeveloped2. In particular, a robust and general method for the direct deoxygenative coupling of alcohols would have major implications for the field of organic synthesis. A general method for the direct deoxygenative cross-coupling of free alcohols must overcome several challenges, most notably the in situ cleavage of strong C-O bonds3, but would allow access to the vast collection of commercially available, structurally diverse alcohols as coupling partners4. We report herein a metallaphotoredox-based cross-coupling platform in which free alcohols are activated in situ by N-heterocyclic carbene salts for carbon-carbon bond formation with aryl halide coupling partners. This method is mild, robust, selective and most importantly, capable of accommodating a wide range of primary, secondary and tertiary alcohols as well as pharmaceutically relevant aryl and heteroaryl bromides and chlorides. The power of the transformation has been demonstrated in a number of complex settings, including the late-stage functionalization of Taxol and a modular synthesis of Januvia, an antidiabetic medication. This technology represents a general strategy for the merger of in situ alcohol activation with transition metal catalysis.

SUBMITTER: Dong Z 

PROVIDER: S-EPMC8643278 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

Metallaphotoredox-enabled deoxygenative arylation of alcohols.

Dong Zhe Z   MacMillan David W C DWC  

Nature 20210831 7881


Metal-catalysed cross-couplings are a mainstay of organic synthesis and are widely used for the formation of C-C bonds, particularly in the production of unsaturated scaffolds<sup>1</sup>. However, alkyl cross-couplings using native sp<sup>3</sup>-hybridized functional groups such as alcohols remain relatively underdeveloped<sup>2</sup>. In particular, a robust and general method for the direct deoxygenative coupling of alcohols would have major implications for the field of organic synthesis. A  ...[more]

Similar Datasets

| S-EPMC6772128 | biostudies-literature
| S-EPMC11599925 | biostudies-literature
| S-EPMC8161533 | biostudies-literature
| S-EPMC11474587 | biostudies-literature
| S-EPMC7219561 | biostudies-literature
| S-EPMC10624253 | biostudies-literature
| S-EPMC11808478 | biostudies-literature
| S-EPMC7801780 | biostudies-literature
| S-EPMC8433232 | biostudies-literature
| S-EPMC9771944 | biostudies-literature