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

A Ti(Oi-Pr) 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.