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

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.

Automated summary

An asymmetric Michael addition of malononitrile to vinyl phosphonates was achieved using hydrogen bond-enhanced bifunctional halogen bond (XB) catalysis, demonstrating the key role of halogen bonding in activation of the Michael acceptors through the phosphonate group. This is the first example of using XBs for activating organophosphorus compounds in synthesis. The iodo-perfluorophenyl group was found to be a better directing unit than different iodo- and nitro-substituted phenyl groups, leading to excellent yields, diastereoselectivities, and good enantioselectivities in the products.