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Highly Enantioselective Construction of a Quaternary Carbon Center of Dihydroquinazoline by Asymmetric Mannich Reaction and Chiral Recognition
Author(s) -
Jiang Biao,
Dong Jia Jia,
Si Yu Gui,
Zhao Xiao Long,
Huang Zuo Gang,
Xu Min
Publication year - 2008
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200800039
Subject(s) - enantioselective synthesis , chemistry , enantiopure drug , quaternary carbon , mannich reaction , ketone , enantiomer , trifluoromethyl , regioselectivity , combinatorial chemistry , medicinal chemistry , organic chemistry , stereochemistry , catalysis , alkyl
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).