Synfacts 2009(2): 0147-0147  
DOI: 10.1055/s-0028-1087573
Synthesis of Heterocycles
© Georg Thieme Verlag Stuttgart ˙ New York

Direct Catalytic Asymmetric Synthesis of Cyclic Aminals from Aldehydes

Contributor(s): Victor Snieckus, Timothy Hurst
X. Cheng, S. Vellalath, R. Goddard, B. List*
Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany
Further Information

Publication History

Publication Date:
22 January 2009 (online)


Reported is the asymmetric synthesis of quinazolinones 3 and benzo(thia)diazines 6 from the reaction of 2-aminobenzamides 1 or 2-aminobenzenesulfonamides 4 with aldehydes 2 or 5 under chiral Brønsted acid catalysis. Investigation of several potential chiral phosphoric acid catalysts led to identification of the anthracenyl-modified TRIP catalyst 7 as the optimal reagent. Although high yields and enantioselectivities were obtained using aliphatic, α-unbranched aldehydes, branched and aromatic aldehydes gave somewhat lower enantioselectivities. A broad range of aromatic functional groups are tolerated, including strongly electron-donating and -withdrawing substituents. The methodology was also applied to the synthesis of several members of the benzo(thia)diazines, a known class of pharmaceuticals commonly employed for the treatment of high blood pressure.