When the enamine component is changed from 162 to 1-(1-pyrrolidinyl)-cyclohexene (166), 52 affords 3-hydroxy-Nb-methoxycarbonyl-2-(1-pyrroli-dinyl)-3H-indole-3-ethanamine (167, 38%) as a sole isolable product. Similarly, 1-hydroxy-N,N-dimethylindole-3-acetamide (168a) provides 3-hydroxy-N,N-dimethyl-2-(1-pyrrolidinyl)-3H-indole-3-acetamide (169, 21%) and N,N-dimethylindole-3-acetamide (168b, 26%). The structure of 167 is determined by X-ray single-crystal analysis.

Scheme 22 A plausible mechanism for the tosyl chloride-mediated reaction of 1-hydroxy-tryptamines with enamines

A plausible mechanism for the formations of 164, 165, and 167 is shown in Scheme 22 [40]. Following the route a, an initially attempted reaction pathway, the tosylation of 52 occurs. Subsequent nucleophilic attack of the enamine (166) on the resultant tosylate (170) at the 3-position can afford 164 through 171 after work-up. Compound (165) is the product of [3,7] sigmat-ropic rearrangement of 170.

On the other hand, following the route b, the tosylation of the enamine (166) would occur simultaneously with the attack by the 1-hydroxy oxygen of 52 to generate the intermediate (172), in which the nitrogen lone pair orbital of pyrrolidine can interact with the n-orbital (2,3-bond) of indole. Subsequent acid catalyzed O - N bond cleavage results in the formation of 173 following the electron movement as shown by the curved arrows. The highly electron-rich compound (173) would be oxidized to the final product (167) through intermediates (174) and (175) under atmospheric oxygen.

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