Highly Enantioselective Construction of a Quaternary Carbon Center of Dihydroquinazoline by Asymmetric Mannich Reaction and Chiral Recognition

Abstract

Abstract 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 ‐ Brønsted acid‐catalyzed enantioselective and regioselective Mannich reaction of a methyl ketone and 4‐trifluoromethyldihydroquinazoline. 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).