Enantioselective Michael addition to vinyl phosphonates via hydrogen bond-enhanced halogen bond catalysis.

Andrus Metsala,Mikk Kaasik,Ivar Järving,Kristin Erkman,Jevgenija Martõnova,Tõnis Kanger

doi:10.1039/d1sc01029h

Abstract

An asymmetric Michael addition of malononitrile to vinyl phosphonates was accomplished by hydrogen bond-enhanced bifunctional halogen bond (XB) catalysis. NMR titration experiments were used to demonstrate that halogen bonding, with the support of hydrogen-bonding, played a key role in the activation of the Michael acceptors through the phosphonate group. This is the first example of the use of XBs for the activation of organophosphorus compounds in synthesis. In addition, the iodo-perfluorophenyl group proved to be a better directing unit than different iodo- and nitro-substituted phenyl groups. The developed approach afforded products with up to excellent yields and diastereoselectivities and up to good enantioselectivities.

Highlights

Halogen bonds (XBs), noncovalent interactions between electrophilic halogen atoms and Lewis bases,[1] are exploited in areas ranging from crystal engineering to catalysis.[2]
Since several studies have demonstrated the viability of XBs to achieve catalysis.[4]
Initial experiments involving vinyl phosphonate 1a and malononitrile 2 (Scheme 1) revealed that no reaction occurred in two days at RT in DCM (Table 1, entry 1)

Summary

Introduction

Halogen bonds (XBs), noncovalent interactions between electrophilic halogen atoms and Lewis bases,[1] are exploited in areas ranging from crystal engineering to catalysis.[2]. The reduction of catalyst loading under the diluted conditions had little effect on the enantioselectivity, yet resulted in a slower reaction (Table 2, entries 3 and 4).

Results

Conclusion