The Regiocontrollable Enantioselective Synthesis of Chiral Trifluoromethyl-Containing Spiro-Pyrrolidine-Pyrazolone Compounds via Amino-Regulated 1,3-Proton Migration Reaction

• DOI: 10.1021/acs.joc.1c01705
• Publication Date: 2021-09-08T15:02:01Z
• Authors: Yabo Deng; Zhenghao Dong; Fengyun Gao; Yifei Guo; Mengmeng Sun; Yongzhen Li; Yalan Wang; Qushuo Chen; Kairong Wang; Wenjin Yan
• Keywords: Squaramide; Pyrrolidine; Diethyl malonate; Stereocenter; Pyrazolones; Aldol reaction; Michael reaction; Malonate

An amino-controlled regiodivergent asymmetric synthesis of CF3-containing spiro-pyrrolidine-pyrazolone compounds is described. With alkaloid-derived squaramide as catalyst, the 1,3-dipolar cycloaddition α,β-unsaturated pyrazolone with diethyl 2-((2,2,2-trifluoroethyl)imino) malonate offered adducts in excellent yields, dr, and ee. While cyclohexanediamine-derived was employed, reaction afforded a series structure isomers through switched umpolung reaction.