Catalytic Enantioselective Synthesis of N-C Axially Chiral Mebroqualone and Its Derivatives through Reductive Asymmetric Desymmetrization

In the presence of (R)-DTBM-SEGPHOS-Pd(OAc)(2) catalyst, treatment of various 3-(2,6-dibromophenyl)-quinazolin-4-ones with NaBH4 gave optically active N-C axially chiral quinazolinone (mebroqualone) derivatives through reductive asymmetric desymmetrization (enantioselective monohydrodebromination) followed by kinetic resolution of the resulting monobromophenyl products (up to 99% ee). The enantioselectivity strongly depended on the substituent (R-2) at the C4'position, amount of NaBH4, and reaction temperature.