期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 61, 期 34, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202206800
关键词
Azacycles; Carboamination; Carbocations; Hexafluoroisopropanol; Lewis Acid Catalysis
资金
- EPSRC Centre for Doctoral Training in Synthesis for Biology and Medicine [EP/L015838/1]
- AstraZeneca
- Diamond Light Source
- Defence Science and Technology Laboratory
- Evotec
- GlaxoSmithKline
- Janssen
- Novartis
- Pfizer
- Syngenta
- Takeda
- UCB
- Vertex
A Ti(Oi-Pr)(4)-promoted 5- or 6-endo-trig cyclization for the synthesis of nitrogen heterocycles is presented. The use of HFIP as a key solvent enables the stereoselective formation of di- and tri-substituted pyrrolidines and piperidines while simultaneously forming a new C-C bond. The process involves the generation of a cationic intermediate 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, different substituents on a nucleophilic amine yield either 2,3-trans- or 2,3-cis-substituted heterocycles. Lastly, enantiopure products can be obtained by using readily available enantiopure acyclic starting materials.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据