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) catalyst, treatment of various 3-(2,6-dibromophenyl)quinazolin-4-ones with NaBH 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) at the C4'position, amount of NaBH, and reaction temperature.