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Hexafluoroisopropanol‐Promoted Haloamidation and Halolactonization of Unactivated Alkenes
Author(s) -
Qi Chenxiao,
Force Guillaume,
Gandon Vincent,
Lebœuf David
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202010846
Subject(s) - pyrrolidine , piperidine , enantioselective synthesis , chemistry , halide , reactivity (psychology) , mechanism (biology) , combinatorial chemistry , computational chemistry , organic chemistry , catalysis , epistemology , philosophy , medicine , alternative medicine , pathology
Abstract Pyrrolidine and piperidine derivatives bearing halide functional groups are prevalent building blocks in drug discovery as halides can serve as an anchor for post‐modifications. In principle, one of the simplest ways to build these frameworks is the haloamination of alkenes. While progress has been made in this field, notably with the development of enantioselective versions, this reaction is still fraught with limitations in terms of reactivity. Besides, a major question remaining is to understand the mechanism at work. The formation of a haliranium intermediate is typically mentioned, but limited mechanistic evidence supports it. Reported here is an efficient metal‐ and oxidant‐free protocol to achieve the haloamidation of olefins, promoted by hexafluoroisopropanol, along with a DFT investigation of the mechanism. These findings should guide the future development of more complex transformations in the field of halofunctionalization.