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

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 of alpha,beta-unsaturated pyrazolone with diethyl 2-((2,2,2-trifluoroethyl)imino) malonate offered adducts in excellent yields, dr, and ee. While the cyclohexanediamine-derived squaramide was employed, the reaction afforded a series of structure isomers through a switched umpolung reaction.

Automated summary

An amino-controlled regiodivergent asymmetric synthesis of CF3-containing spiro-pyrrolidine-pyrazolone compounds is described, offering adducts in excellent yields, dr, and ee when using alkaloid-derived squaramide as the catalyst. Switching to cyclohexanediamine-derived squaramide led to the formation of a series of structural isomers through a switched umpolung reaction.