biostudies-literatureCox LEngineering and Physical Sciences Research Councile202206800https://www.ebi.ac.uk/biostudies/studies/S-EPMC9546487biostudies-literatureUnknown61(34)A Ti(Oi-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.Angewandte Chemie (International ed. in English)Alcohols as Alkylating Agents in the Cation-Induced Formation of Nitrogen Heterocycles.PMC9546487EP/L015838/1Donohoe TJSidera Portela MZhu YChristensen KECox LSmith PJfalseAlcohols as Alkylating Agents in the Cation-Induced Formation of Nitrogen Heterocycles.A Ti(Oi-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.2022-01-01T00:00:00Z2022 Aug2025-04-04T20:04:40.05Z2025-04-04T20:04:40.05ZS-EPMC95464873577071010.1002/anie.202206800