Multifunctional Catalysts in the Asymmetric Mannich Reaction of Malononitrile with N-Phosphinoylimines: Coactivation by Halogen Bonding versus Hydrogen Bonding

A multifunctional (noncovalent) catalyst containinghalogen-bond donor, hydrogen-bond donor, and Lewis basic siteswas developed and applied in an enantioselective Mannich reactionbetween malononitrile and diphenylphosphinoyl-protected aldi-mine affording products in high yields (up to 98%) and moderateto high enantiomeric purities (ee up to 89%). Typically,noncovalent catalysts rely on several weak interactions to activatethe substrate, with one or two of these giving the most notablecontribution to activation. In this instance, instead of the initiallyproposed coactivation by halogen bonding, it was revealed thathydrogen bonding plays a key role in determining theenantioselectivity.

Automated summary

A multifunctional catalyst containing halogen-bond donor, hydrogen-bond donor, and Lewis basic sites was developed and successfully applied in an enantioselective Mannich reaction between malononitrile and diphenylphosphinoyl-protected aldimine. It was found that hydrogen bonding played a key role in determining the enantioselectivity, contrary to the initially proposed coactivation by halogen bonding.