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

• DOI: 10.1021/acs.joc.9b02176
• Publication Date: 2019-11-08T13:40:46Z
• Authors: Chen Chen; Ran Wei; Xing Yi; Li Gao; Min Zhang; Han Liu; Qingshan Li; Heng Song; Shurong Ban
• Keywords: POTENT; SQUARAMIDE DERIVATIVES; CARBOCYCLIC NUCLEOSIDE ANALOG; 01 natural sciences; 0104 chemical sciences

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).