alpha-t-butyl- and alpha-i-propyl-ortho-hydroxybenzylamines: Racemic synthesis/resolution and asymmetric synthesis

Efficient routes to alpha-tert-butyl- and alpha-iso-propyl-ortho-hydroxyben zylamines 1a and 1b are described. Highly enantioenriched 1a and 1b were ob tained by resolution of the methoxy derivatives 2 by recrystallization of t he salts formed with mandelic acid followed by Lewis acid mediated demethyl ation. The chiral 1,3-amino alcohol 1a has also been obtained in an asymmet ric synthesis with the key step a diastereoselective alkylation of the imin e obtained by condensation of o-anisaldehyde with phenyl glycinol. The abso lute stereochemistry of these 1,3-aminophenols was determined by CD spectro scopy of the salicylideneamines 12 and by an X-ray structure analysis of th e salt formed between (R)-mandelic acid and (S)-alpha-tert-butyl-ortho-meth oxybenzylamine ((S)-2a). (C) 2000 Wiley-Liss, Inc.