Asymmetric Synthesis of 2,3-Dihydropyrroles by Ring-Opening/Cyclization of Cyclopropyl Ketones Using Primary Amines

• Published in: Angewandte Chemie International Edition Vol. 54; no. 1; pp. 227 - 230
• Main Authors: Xia, Yong, Liu, Xiaohua, Zheng, Haifeng, Lin, Lili, Feng, Xiaoming
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 02-01-2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Amines; Amines - chemistry; Asymmetric synthesis; Asymmetry; Catalysis; Cyclization; Ketones; Ketones - chemistry; kinetic resolution; N,N′‐dioxides; Nucleophiles; N′-dioxides; Organic compounds; Oxides - chemistry; Pyrroles - chemical synthesis; Pyrroles - chemistry; Reaction kinetics; ring opening; Scandium; Scandium - chemistry; Substrates; Synthesis; kinetic resolution; scandium; N,N′-dioxides; ring opening; cyclization
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201407880

The asymmetric ring‐opening/cyclization of cyclopropyl ketones with primary amine nucleophiles was catalyzed by a chiral N,N′‐dioxide/scandium(III) complex through a kinetic resolution process. A broad range of cyclopropyl ketones and primary amines are suitable substrates of this reaction. The corresponding products were afforded in excellent enantioselectivities and yields (up to 97 % ee and 98 % yield) under mild reaction conditions. This method provides a promising access to chiral 2,3‐dihydropyrroles as well as an effective procedure for the kinetic resolution of 2‐substituted cyclopropyl ketones.
2,3‐Dihydropyrroles are obtained in high yields and enantioselectivities through an enantioselective ring‐opening/cyclization reaction of substituted cyclopropyl ketones with primary amine nucleophiles under mild reaction conditions. This method also provides an effective procedure for the kinetic resolution of 2‐substituted cyclopropyl ketones.