Migratory functionalization of unactivated alkyl bromides for construction of all-carbon quaternary centers via transposed tert-C-radicals.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32978381.
- Also identified by DOI 10.1038/s41467-020-18658-4 and PMC identifier 7519689.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Despite remarkable recent advances in transition-metal-catalyzed C(sp<sup>3</sup>)-C cross-coupling reactions, there remain challenging bond formations. One class of such reactions include the formation of tertiary-C(sp<sup>3</sup>)-C bonds, presumably due to unfavorable steric interactions and competing isomerizations of tertiary alkyl metal intermediates. Reported herein is a Ni-catalyzed migratory 3,3-difluoroallylation of unactivated alkyl bromides at remote tertiary centers. This approach enables the facile construction of otherwise difficult to prepare all-carbon quaternary centers. Key to the success of this transformation is an unusual remote functionalization via chain walking to the most sterically hindered tertiary C(sp<sup>3</sup>) center of the substrate. Preliminary mechanistic and radical trapping studies with primary alkyl bromides suggest a unique mode of tertiary C-radical generation through chain-walking followed by Ni-C bond homolysis. This strategy is complementary to the existing coupling protocols with tert-alkyl organometallic or -alkyl halide reagents, and it enables the expedient formation of quaternary centers from easily available starting materials.