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 phthaloyl‐protected amino acid chlorides to form N ‐acyliminium intermediates, which, in the presence of titanium alkoxides at room temperature, undergo Pictet–Spengler reactions to give tetrahydro‐β‐carbolines with diastereomeric ratios of up to 99:1. The chiral auxiliary can be removed from the Pictet–Spengler adducts by means of a simple reduction. To rationalize the observed stereoselectivity a transition‐state model is proposed in which the titanium atom coordinates both the carbonyl group of the N ‐acyliminium ion and the amino acid protecting group.