Migratory functionalization of unactivated alkyl bromides for construction of all-carbon quaternary centers via transposed tert-C-radicals

Despite remarkable recent advances in transition-metal-catalyzed C(sp 3 )−C cross-coupling reactions, there remain challenging bond formations. One class of such reactions include the formation of tertiary -C(sp 3 )−C bonds, presumably due to unfavorable steric interactions and competing isomerizati...

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Published in:Nature communications 2020-09, Vol.11 (1), p.4860-4860, Article 4860
Main Authors: Zhu, Chuan, Liu, Ze-Yao, Tang, Luning, Zhang, Heng, Zhang, Yu-Feng, Walsh, Patrick J., Feng, Chao
Format: Article
Language:English
Subjects:
140/131
140/58
639/638
639/638/77
639/638/77/885
639/638/77/888
Humanities and Social Sciences
multidisciplinary
Science
Science (multidisciplinary)
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Summary:Despite remarkable recent advances in transition-metal-catalyzed C(sp 3 )−C cross-coupling reactions, there remain challenging bond formations. One class of such reactions include the formation of tertiary -C(sp 3 )−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 3 ) 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. Formation of tertiary C(sp 3 )-C bonds is a formidable challenge due to steric interactions and low barriers for isomerization of intermediates. Here, the authors show a Ni-catalyzed migratory 3,3-difluoroallylation of unactivated alkyl bromides at remote tertiary carbon centers.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-18658-4