Enantiospecific synthesis with amino acids. Part 2. α-Alkylation of tryptophan: a chemical and computational investigation of cyclic tryptophan tautomers

Abstract

The tautomerisation of various α-substituted tryptamine and tryptophan carbamates in trifluoroacetic acid/chloroform to the corresponding hexahydropyrrolo[2,3-b]indoles is studied by ¹H NMR spectroscopy and force field calculations in an attempt to understand the thermodynamic preference of substitutents at C-2 in the latter system for the endo-face. The calculations agree with experiment as to the thermodynamic nature of the selectivities observed, but fail to predict accurately the equilibrium ratios. It is concluded that the ratios are affected by factors not taken into account in the calculation and it is suggested that these factors may be entropic resulting from differential solvation of the endo and exo substituted systems.