Water as an efficient medium for the synthesis of tetrahydro-β-carbolines via Pictet-Spengler reactions

A mild and efficient protocol for the Pictet-Spengler reaction in water using an acid catalyst has been described. The condensation of tryptophan, tryptamine, and N-b-benzyl tryptophan with different aldehydes having both electron-withdrawing and -donating substituents in the presence of a catalytic amount of TFA in water furnished tetrahydro-beta-carbolines in good isolated yields. A salient feature of the water mediated Pictet-Spengler reaction was the general trend observed during the condensation of Trp-OMe and aryl/aliphatic aldehydes furnishing diastereomeric mixtures with a preference for the cis-isomer. (c) 2007 Elsevier Ltd. All rights reserved.