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

Chen Chen; Ran Wei; Xing Yi; Li Gao; Min Zhang; Han Liu; Qingshan Li; Heng Song; Shurong Ban

doi:10.1021/acs.joc.9b02176

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

J Org Chem. 2019 Dec 6;84(23):15655-15661. doi: 10.1021/acs.joc.9b02176. Epub 2019 Nov 18.

Authors

Chen Chen¹, Ran Wei¹, Xing Yi¹, Li Gao¹, Min Zhang¹, Han Liu², Qingshan Li¹, Heng Song^{1

3}, Shurong Ban¹

Affiliations

¹ School of Pharmacy , Shanxi Medical University , Taiyuan 030001 , China.
² Department of Chemistry , Aarhus University , Aarhus C 8000 , Denmark.
³ College of Chemistry and Molecular Sciences , Wuhan University , Wuhan 430072 , China.

PMID: 31702146
DOI: 10.1021/acs.joc.9b02176

Abstract

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).

Publication types

Research Support, Non-U.S. Gov't