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

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.