Synthesis of Chiral Phosphorus Reagents and Their Application in Combination With Lewis Acid as a Cocatalyst in Morita–Baylis–Hillman Reaction

Abstract

Two novel chiral thiophosphoramides and two chiral phosphoramidites were synthesized starting from (S)-α-phenylethylamine and (R)-(+) or (S)-(−)-1,1′-Bi-2-naphthol (BINOL), respectively, and their application in combination with Lewis acid as cocatalysts in asymmetric Morita–Baylis–Hillman (MBH) reaction was investigated. Dramatic rate acceleration (the corresponding adducts were obtained in fair to excellent chemical yield within 15 min–5 h) was observed in these chiral phosphorus reagents/Lewis acid cocatalyzed MBH reaction between 4-nitrobenzaldehyde and activated alkenes, and in one case, moderate enantioselectivity was achieved (the corresponding adduct's ee value is 44%).

GRAPHICAL ABSTRACT

Keywords:

• Activated alkenes
• chiral phosphoramidites
• chiral thiophosphoramides
• Morita–Baylis–Hillman reaction
• 4-nitrobenzaldehyde

Acknowledgments

This work is supported by the Research Fund for Young Scientist (No. 52LX29), the special research program for Tianjin Binhai New Area (No. 52LE14) Tianjin Normal University, and Natural Science Foundation of Tianjin (No. 08JCYBJC26900), Tianjin.