Studies in sigmatropic rearrangements of N-prenylindole derivatives - A formal enantiomerically pure synthesis of tryprostatin B

Rearrangement of N^a-prenyl-N^b-acetyltryptamine, induced by BF₃·Et₂O at low temperature, leads to a 2-prenyl derivative, and thence to the tricyclic tryptamine 7 and the indoline 8. Similarly, N^a-prenyl-N^b-phthaloyl-l-tryptophan methyl ester furnished the corresponding 2-prenyl derivative 16, a known advanced precursor of tryprostatin B. Density functional (B3LYP) calculations for the putative rearrangement transition state for N-prenylskatole show that prior coordination of BF₃ to the indolic nitrogen changes the character of the subsequent sigmatropic pericyclic shifts from being entirely covalent to acquiring a significant degree of ionic character. The shifting prenyl group favours the endo over the exo mode of the transition state by 4.1 kcal mol ^-1.