Synthesis of Azepino[4,5-b]indolones via Radical-Mediated Tryptamine Substitution

Significance

Reported is the synthesis of azepino[4,5-b]indolones using a radical-based C2-tryptamine alkylation as a key step. The mechanism of the reaction was not investigated as the use of xanthates and peroxides in radical reactions has been the subject of previous investigation and use by the Zard group (referenced well in the current work). In this previous work, catalytic amounts of peroxide initiator were used. However, several equivalents were necessary since it was also the oxidant involved in rearomatization. Although a tertiary xanthate was also used in the alkylation, the yields of this reaction were low and a more efficient procedure using a secondary xanthate with K₂CO₃ and an alkylating agent (MeI or BnBr) was developed for the preparation of the more highly substituted products. Interestingly, when the diesters were cyclized, azepine ring ­hydroxylation was observed. Although a precedent for a similar hydroxylation using much harsher conditions was given, no explanation for this phenomenon was provided.