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α‐ t ‐butyl‐ and α‐ i ‐propyl‐ ortho ‐hydroxybenzylamines: Racemic synthesis/resolution and asymmetric synthesis
Author(s) -
Bernardinelli Gérald,
Fernandez Daniel,
Gosmini Romain,
Meier Peter,
Ripa Alberto,
Schüpfer Patrick,
Treptow Björn,
Kündig E. Peter
Publication year - 2000
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(2000)12:5/6<529::aid-chir41>3.0.co;2-3
Subject(s) - chemistry , mandelic acid , alkylation , imine , enantioselective synthesis , medicinal chemistry , kinetic resolution , absolute configuration , alcohol , stereochemistry , chiral resolution , organic chemistry , enantiomer , catalysis
Efficient routes to α‐ tert ‐butyl‐ and α‐ 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 )‐α‐ tert ‐butyl‐ ortho ‐methoxybenzylamine (( S )‐ 2a ). Chirality 12:529–539, 2000. © 2000 Wiley‐Liss, Inc.