Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters

被引：42

作者：

Shi, Yongjie ^{[1
,2
,4
]}

Tan, Xuefeng ^{[1
,2
]}

Gao, Shuang ^{[1
,2
]}

Zhang, Yao ^{[1
,2
]}

Wang, Jingxin ^{[1
,2
]}

Zhang, Xumu ^{[1
,2
]}

Yin, Qin ^{[1
,2
,3
]}

机构：

[1] Southern Univ Sci & Technol, Shenzhen Grubbs Inst, Shenzhen 518055, Peoples R China

[2] Southern Univ Sci & Technol, Dept Chem, Shenzhen 518055, Peoples R China

[3] Southern Univ Sci & Technol, Acad Adv Interdisciplinary Studies, Shenzhen 518055, Peoples R China

[4] Univ Hong Kong, Dept Chem, State Key Lab Synthet Chem, Hong Kong, Peoples R China

来源：

ORGANIC LETTERS | 2020年 / 22卷 / 07期

基金：

中国国家自然科学基金;

关键词：

ALKYL-ARYL KETONES; ENANTIOSELECTIVE SYNTHESIS; LEVULINIC ACID; GAMMA-LACTAMS; TRANSFER HYDROGENATION; COOPERATIVE CATALYSIS; PRIMARY AMINES; BRONSTED ACID; AMINATION; PYRROLIDINONES;

D O I：

10.1021/acs.orglett.0c00669

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology.

引用

页码：2707 / 2713

页数：7

共 73 条

[1] Asymmetric Alkynylation/Lactamization Cascade: An Expeditious Entry to Enantiomerically Enriched Isoindolinones [J].