Affiliation:
1. Institute of Molecular Sciences and Engineering Institute of Frontier and Interdisciplinary Science Shandong University Qingdao Shandong 266237 China
2. School of Chemistry and Chemical Engineering Shaanxi Normal University Xi'an 710062 China
Abstract
AbstractThe incorporation of fluorine atoms in organics improves their bioactivity and lipophilicity. Catalytic functionalization of gem‐difluorodienes represents one of the most straightforward approaches to access fluorinated alkenes. In contrast to the regular 1,3‐dienes that undergo diverse asymmetric di/hydrofunctionalizations, the regio‐ and enantioselective oxyamination of gem‐difluorodienes remains untouched. Herein, we report asymmetric 1,4‐oxyamination of gem‐difluorodiene by chiral rhodium‐catalyzed three‐component coupling with readily available carboxylic acid and dioxazolone, affording gem‐difluorinated 1,4‐amino alcohol derivatives. Our asymmetric protocol exhibits high 1,4‐regio‐ and enantioselectivity with utility in the late‐stage modification of pharmaceuticals and natural products. Stoichiometric experiments provide evidences for the π‐allylrhodium pathway. Related oxyamination was also realized when trifluoroethanol was used as an oxygen nucleophile.
Funder
National Key Research and Development Program of China
Subject
General Chemistry,Catalysis