Enantioselective Halogenative Semi-Pinacol Rearrangement: Extension of Substrate Scope and Mechanistic Investigations

The present Full Paper article discloses a survey of our recent results obtained in the context of the enantioselective halogenation‐initiated semi‐pinacol rearrangement. Commencing with the fluorination/semi‐pinacol reaction first and moving to the heavier halogens (bromine and iodine) second, the scope and limitations of the halogenative phase‐transfer methodology will be discussed and compared. An extension of the fluorination/semi‐pinacol reaction to the ring‐expansion of five‐membered allylic cyclopentanols will be also described, as well as some preliminary results on substrates prone to desymmetrization will be given. Finally, the present manuscript will culminate with a detailed mechanistic investigation of the canonical fluorination/semi‐pinacol reaction. Our mechanistic discussion will be based on in situ reaction progress monitoring, complemented with substituent effect, kinetic isotopic effect and non‐linear behaviour studies. Scope and limitations of the fluorination‐initiated semi‐pinacol rearrangement of strained, prochiral allylic alcohols are described. This reaction is proposed to operate through anionic phase‐transfer technology, and can be readily extended to the heavier halogen (Br, I) congeneers. In comparison with the fluorination reaction, an intriguing inversion of the sense of absolute induction for the heavier halogens is described (see scheme).