Alcohols as Alkylating Agents in the Cation‐Induced Formation of Nitrogen Heterocycles

Abstract A Ti(O i ‐Pr) 4 promoted 5‐ or 6‐ endo ‐trig cyclisation to make nitrogen heterocycles is presented. The utilisation of HFIP as a key solvent enables the stereoselective preparation of di‐ & tri‐substituted pyrrolidines and piperidines while forming a new C−C bond at the same time. The process is triggered by a cationic intermediate generated from an allylic or benzylic alcohol and leads to the simultaneous generation of both a C−C and a C−N bond in a single step. Notably, either 2,3‐ trans‐ or 2,3‐ cis ‐substituted heterocycles can be obtained by using a nucleophilic amine bearing different substituents. Lastly, the stereoselective synthesis of enantiopure products was achieved by using readily available enantiopure acyclic starting materials.