Hexafluoroisopropanol‐Promoted Haloamidation and Halolactonization of Unactivated Alkenes

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. The use of hexafluoroisopropanol (HFIP) as an additive enables the halofunctionalization of unactivated alkenes with a remarkable functional‐group tolerance under mild reaction conditions. DFT computations were carried out to shed light on the mechanism of haloamidation, featuring alkene activation assisted by a nitrogen nucleophile as a key step. EWG=electron‐withdrawing group.