Asymmetric synthesis of arylglycines and their use as chiral templates forthe stereocontrolled synthesis of 7,8-disubstituted 3-aryl-1,2,3,4-tetrahydroisoquinolin-4-ols

A synthetic technique for the asymmetric synthesis of arylglycines has been optimized, reaching the target amino acids in only four steps with good yi elds and with enantiomeric excesses higher than 99%. The key step consisted of a stereocontrolled electrophilic amination reaction of (S,S)-(+)pseudoe phedrine-bas ed arylacetamide enolates with di-tert-butylazodicarboxylate. The arylglycines thus obtained turned out to be excellent chiral templates for the production of chiral, nonracemic 7,8-disubstituted 3-aryl-1,2,3,4-t etrahydroisoquinolines, through use of a synthetic sequence involving: (1) reduction of the arylglycines to the parent arylglycinols, (2) N-benzylatio n with appropriately substituted aromatic aldehydes and (3) Swern oxidation followed by acid-catalysed cyclization of the obtained a-amino aldehydes.