Synthesis of Pyrrolo-imidazoindoles from Tryptophan Methyl Ester

Significance

The stereoselective acid-promoted sequential double cyclization of tryptophan-based α-amino nitriles, derived from either ketones or aldehydes, to novel hexahydropyrrolo[1′,2′,3′:1,9a,9]imidazo[1,2-a]indoles is described. The precursors are prepared by in situ Yb(OTf)₃-promoted cyanation of intermediate Schiff bases. The cyclization undoubtedly proceeds by normal indole 3-Lewis-acid activation followed by trap of the iminium species and indole-N by the side chain amino and nitrile functions. Two or three stereogenic centers are formed in a single step. The exo-isomer is produced under kinetically controlled conditions and can be converted into the corresponding endo-isomer under thermodynamic control.