Cis-Diastereoselectivity in Pictet-Spengler Reactions of L-Tryptophan and Electronic Circular Dichroism Studies

The diastereoselective synthesis of optically active 1,3-disubstituted tetrahydro-beta-carbolines using polar protic PictetSpengler cyclization of (S)-tryptophan methyl ester with five aldehydes RCHO (R-CH3, C2H5, C3H7, C4H9, and C6H5) was studied. As an alternate route, the cyclization of (S)-tryptophan with the same aldehydes and subsequent methylation of the resulting tetrahydro-beta-carboline carboxylic acids were also performed for comparison. 13C NMR and electronic circular dichroism (ECD) studies and time-dependent density functional theory ECD calculations data established the relative 1,3 cis/trans and the absolute configuration (1S,3S/ 1R,3S) of the synthesized compounds. The solid-state and solution ECD study of the prepared compounds, supported by ECD calculation and X-ray data, afforded a reliable ECD method for the configurational assignment of 1,3-disubstituted tetrahydro-beta-carbolines and revealed the stereochemical factors that determine the characteristic ECD data. Chirality 24:789795, 2012. (c) 2012 Wiley Periodicals, Inc.