Diastereo- and enantio-selectivity in the Pictet-Spengler reaction

The factors that control the relative and absolute stereochemistry of 1,3-disubstituted and 1,2,3-trisubstituted tetrahydro-ß-carbolines formed via the Pictet-Spengler reaction are discussed. In particular, the stereochemical factors that lead to the predominance of cis-1,3-disubstituted products under conditions of kinetic control are presented, with the aid of X-ray crystallographic data on a number of compounds; methods for assigning relative stereochemistry on the basis of NMR data are given; the mechanism by which racemisation can occur during the Pictet-Spengler reaction has also been studied, and procedures for eliminating this problem are given.