ASYMMETRIC CONTROL IN THE PICTET-SPENGLER REACTION BY MEANS OF N-PROTECTED AMINO-ACIDS AS CHIRAL AUXILIARY GROUPS

Aromatic and aliphatic Schiff bases of tryptamine react with Fmoc- or ph-thaloyl-protected amino acid chlorides to form N-acyliminium interm ediates, which, in the presence of titanium alkoxides at room temperat ure, undergo Pictet-Spengler reactions to give tetrahydro-beta-carboli nes with diastereomeric ratios of up to 99:1. The chiral auxiliary can be removed from the Pictet-Spengler adducts by means of a simple redu ction. To rationalize the observed stereoselectivity a transition-stat e model is proposed in which the titanium atom coordinates both the ca rbonyl group of the N-acyliminium ion and the amino acid protecting gr oup.