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-hydroxybenzylamines 1a and 1b are described. Highly enantioenriched 1a and 1b were obtained by resolution of the methoxy derivatives 2 by recrystallization of the salts formed with mandelic acid followed by Lewis acid mediated demethylation. The chiral 1,3-amino alcohol 1a has also been obtained in an asymmetric synthesis with the key step a diastereoselective alkylation of the imine obtained by condensation of o-anisaldehyde with phenyl glycinol. The absolute stereochemistry of these 1,3-aminophenols was determined by CD spectroscopy of the salicylideneamines 12 and by an X-ray structure analysis of the salt formed between (R)-mandelic acid and (S)-alpha-tert-butyl-ortho-methoxybenzylamine ((S)-2a).
Bernardinelli
G
G
Department of Organic Chemistry, University of Geneva, Geneva, Switzerland.
Fernandez
D
D
Gosmini
R
R
Meier
P
P
Ripa
A
A
Schüpfer
P
P
Treptow
B
B
Kündig
E P
EP