Stereo- and regioselectivity in asymmetric synthesis of α-amino substituted benzocyclic compounds

Abstract

The enantiomerically pure chiral benzocyclic amines 6– 8 were obtained by asymmetric transamination of the corresponding prochiral ketones 9a– c. The method involves: (a) formation of chiral imines 10a– c from the prochiral ketones 9a– c and the inexpensive chiral auxiliary ( R)- or ( S)-phenylethylamine (PEA); (b) asymmetrically induced reduction of these imines to the diastereomeric amines 11a– c and 12a– c; (c) catalytic hydrogenation to remove the benzylic fragment of the chiral PEA auxiliary. The stereoselectivity of the imine reduction, as well as the regioselectivity of the catalytic hydrogenation, are strongly dependent on the size of the saturated ring condensed with the benzene ring. This approach was used to develop a convenient, high yielding, and stereoselective route to several practically important optically active α-amino substituted benzocyclic compounds.