Abstract

Installation of fluorine into pharmaceutically relevant molecules plays a vital role in their properties of biology or medicinal chemistry. Direct difunctionalization of alkenes and 1,3-dienes to achieve fluorinated compounds through transition-metal catalysis is challenging, due to the facile β-H elimination from the Csp3‒[M] intermediate. Here we report a cobalt-catalyzed regioselective difluoroalkylarylation of both activated and unactivated alkenes with solid arylzinc pivalates and difluoroalkyl bromides through a cascade Csp3‒Csp3/Csp3‒Csp2 bond formation under mild reaction conditions. Indeed, a wide range of functional groups on difluoroalkyl bromides, olefins, 1,3-dienes as well as (hetero)arylzinc pivalates are well tolerated by the cobalt-catalyst, thus furnishing three-component coupling products in good yields and with high regio- and diastereoselectivity. Kinetic experiments comparing arylzinc pivalates and conventional arylzinc halides highlight the unique reactivity of these organozinc pivalates. Mechanistic studies strongly support that the reaction involves direct halogen atom abstraction via single electron transfer to difluoroalkyl bromides from the in situ formed cobalt(I) species, thus realizing a Co(I)/Co(II)/Co(III) catalytic cycle.

Transition metal-catalyzed regioselective difunctionalizations of alkenes with two different functional groups are useful for preparing organic compounds, but the construction of two new C–C bonds is challenging. Here, the authors report cobalt-catalyzed regioselective difluoroalkylarylation of alkenes with solid arylzinc pivalates and difluoroalkyl bromides, through a cascade Csp3 ‒Csp3/Csp3 ‒Csp2 bond formation.

Details

Title
Organozinc pivalates for cobalt-catalyzed difluoroalkylarylation of alkenes
Author
Cheng, Xinyi 1 ; Liu Xingchen 1 ; Wang Shengchun 2 ; Hu, Ying 1 ; Hu Binjing 1 ; Lei Aiwen 2   VIAFID ORCID Logo  ; Li, Jie 1 

 Soochow University, Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Suzhou, People’s Republic of China (GRID:grid.263761.7) (ISNI:0000 0001 0198 0694) 
 Wuhan University, College of Chemistry and Molecular Sciences, the Institute for Advanced Studies (IAS), Wuhan, People’s Republic of China (GRID:grid.49470.3e) (ISNI:0000 0001 2331 6153) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2552182452
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.