Hydrogen-Bonding Cyclodiphosphazane Organocatalysts in Enantioselective Michael Additions

Abstract Chiral aryl-(1R,2R)-N,N-dimethyldiamino-cyclohexane (DMDACH)-substituted cyclodiphosphazanes are demonstrated to be efficient bifunctional hydrogen-bonding organocatalysts for the enantioselective Michael additions of 2-hydroxy-1,4-naphthoquinone (<90% ee), Meldrum’s acid (<55% ee), and kojic acid chloride (<80% ee) to β-nitrostyrene. The parent, unsubstituted phenyl-cyclodiphosphazane with PO functions shows superior enantioselectivity in most cases and even exceeds, with 55% ee, the enantioselectivity of Takemoto’s thiourea catalyst for the challenging Meldrum’s acid substrate (46% ee). For Michael additions of kojic acid chloride, the meta-CH3-substituted cyclodiphosphazane with PS functions is the most enantioselective (< 80% ee) catalyst. This highlights the benefits of modular cyclodiphosphazane structures, which can be tailored for specific substrates.