Phase-Transfer-Catalyzed Asymmetric Synthesis of Chiral N-Substituted Pyr­azoles by Aza-Michael Reaction

• Published in: European journal of organic chemistry Vol. 2015; no. 29; pp. 6495 - 6502
• Main Authors: Lee, Su-Jeong, Bae, Ju-Yeon, Cho, Chang-Woo
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01-09-2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Asymmetric catalysis; Enantioselectivity; Nitrogen heterocycles; Phase-transfer catalysis; Synthetic methods
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201500940

An efficient cinchona‐based phase‐transfer‐catalyzed asymmetric aza‐Michael reaction of pyrazole with various α,β‐unsaturated ketones has been developed for the preparation of chiral N‐substituted pyrazoles. This reaction provided the desired products in good yields (up to 99 %) with excellent enantioselectivities (87–94 % ee). In addition, the reaction of 3‐methyl‐1H‐pyrazole, an unsymmetrically substituted pyrazole, was treated with α,β‐unsaturated ketones to afford the corresponding chiral N‐substituted pyrazoles in good yields (up to 99 %) with excellent enantioselectivities (90–92 % ee) and regioisomeric ratios of up to 9:1.
The asymmetric synthesis of chiral N‐substituted pyrazoles has been achieved by phase‐transfer‐catalyzed aza‐Michael reactions of pyrazoles with various α,β‐unsaturated ketones.