Catalytic enantioselective synthesis of β-amino alcohols by nitrene insertion

• 作者: Zijun Zhou Yuqi Tan Xiang Shen Sergei Ivlev Eric Meggers
• 来源期刊: 中国科学：化学（英文版）
• 年，卷（期）: 2021,（3）
• 所属期刊栏目: ARTICLES
• 页码范围: 452-458
• 页数: 7页
• 语种: 英文

摘要

Chiral β-amino alcohols are important building blocks for the synthesis of drugs,natural products,chiral auxiliaries,chiral ligands and chiral organocatalysts.The catalytic asymmetric β-amination of alcohols offers a direct strategy to access this class of molecules.Herein,we report a general intramolecular C(sp3)-H nitrene insertion method for the synthesis of chiral oxazolidin-2-ones as precursors of chiral β-amino alcohols.Specifically,the ring-closing C(sp3)-H amination of N-benzoyloxycarbamates with 2 mol％ of a chiral ruthenium catalyst provides cyclic carbamates in up to 99％ yield and with up to 99％ ee.The method is applicable to benzylic,allylic,and propargylic C-H bonds and can even be applied to completely non-activated C (sp3)-H bonds,although with somewhat reduced yields and stereoselectivities.The obtained cyclic carbamates can subsequently be hydrolyzed to obtain chiral β-amino alcohols.The method is very practical as the catalyst can be easily synthesized on a gram scale and can be recycled after the reaction for further use.The synthetic value of the new method is demonstrated with the asymmetric synthesis of a chiral oxazolidin-2-one as intermediate for the synthesis of the natural product aurantioclavine and chiral β-amino alcohols that are intermediates for the synthesis of chiral amino acids,indane-derived chiral Box-ligands,and the natural products dihydrohamacanthin A and dragmacidin A.