Oxidation of an indoline with Fremy's salt (potassium nitrosodisulfonate) led to the formation of an unstable intermediate which isomerized to the desired 5-hydroxyindole upon standing. This intermediate has been isolated and characterized as an iminoquinone derivative. Identification of this intermediate has allowed us to propose a mechanism for the Fremy's salt mediated oxidation of indolines to 5-hydroxyindoles. O 1997 Elsevier Science Ltd.
During the course of our studies of serotonergic agents, we were interested in preparing the conformationaUy restricted serotonin analogue I and its enantiomer, j The synthesis of (+)-1 has been reported in the patent literature; however the synthetic route is quite lengthy and no method for resolution of (+)-1 has been reported) Since we had ready access to both enantiomers of the indoline derivative 2, 3 we felt the most direct route would involve an oxidative conversion of 2 to 1. The key step in this conversion would involve a Fremy's salt mediated oxidation.
HN~NH2 ~~. NH2
1 2
Fremy's salt (potassium nitrosodisulfonate) is a radical oxidizing agent which is most commonly employed to oxidize phenols to the corresponding benzoquinones. 4 We are also aware of a few reports where it has been used to convert indolines to the corresponding 5-hydroxyindoles. s No mechanism for this interesting reaction has been proposed, although Humber, et ai. 5a reported the formation of an uncharacterized intermediate which was transformed to the desired 5-hydroxyindole upon standing. We report in this communication the isolation and identification of an intermediate in this oxidation process which allows us to draw conclusions about the mechanism of this transformation.