Diastereo- and Enantioselective Synthesis of Functionalized Cyclopentenes Containing a Quaternary Chiral Center via a Thiosquaramide-Catalyzed Cascade Michael–Henry Reaction

An efficient method for the highly diastereoselective synthesis of chiral quaternary center-containing cyclopentenes via a cinchona alkaloid-derived thiosquaramide VIII-catalyzed tandem Michael–Henry reaction of phenacylmalononitriles and nitroolefins was deleveloped. Meanwhile, up to 98% of enantioselectivity was observed. A mechanism involving thiosqaramide-catalyzed asymmetric Michael addition and assisted E2 elimination was proposed based on experimental data and preliminary theoretical analysis (Hartree–Fock calculations).