Insight into the mechanism of the Pictet-Spengler reaction for the synthesis of natural products

ORGN 163

Michael L. Van Linn, mvanlinn@uwm.edu, F. Holger Försterling, and James M. Cook, capncook@uwm.edu. Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, 3210 N. Cramer St., Milwaukee, WI 53211
It is well known that Nb-alkyl tryptophan alkyl esters undergo the Pictet-Spengler reaction with aldehydes to furnish both cis- and trans-1,2,3,4-tetrahydro-β-carbolines, with the trans isomer predominating. Epimerization at C-1 takes place under acidic conditions to produce, exclusively, the thermodynamically more stable trans diastereomer, potentially through a carbocationic intermediate. The epimerization rate has been shown to be sensitive to electronic effects directed toward the C-1 position. In order to determine if the carbocationic intermediate does indeed exist, rate data was obtained for a series of tri-substituted 1-phenyl-1,2,3,4-tetrahydro-β-carbolines. This rate data was applied to the Hammett relationship and σ and σ+ values were compared.