Highly enantioselective construction of a quaternary carbon center of dihydroquinazoline by asymmetric Mannich reaction and chiral recognition

The highly enantioselective construction of a quaternary carbon center of dihydroquinazoline by an asymmetric Mannich reaction and chiral recognition are described. The key transformation was to establish the chiral trifluoromethyl quaternary carbon center by a diamine-Bronsted acid-catalyzed enantioselective and regioselective Mannich reaction of a methyl ketone and 4-trifluoromethyldihydroquinazo-line. An unusual phenomenon of self-discrimination of enantiomers in hydrogen-bonded dimers was observed. A valuable intermediate was transformed into the enantiopure HIV reverse transcriptase inhibitor DPC 083 (> 99.9 ee) simply by reduction of the carbonyl group and elimination of the hydroxy group in hexamethylphosphoric tramide (HMPA).