Indole as a tool in synthesis. Indolenine approach to 4,5-epoxy-10-normorphinans

The 4,5-epoxy-10-normorphinans 2a and 2b featuring the morphine skeleton lacking the B-ring were synthesized using the ''nitrous acid deamination'' of indolenines as the key step. Thus, indolenines 13 and 15 were prepared by Fischer synthesis from the corresponding bicyclic ketolactams 6 and 12, respectively, and further transformed into the related hexahydrodibenzofurans. Ketolactam 6 was obtained from 3-nitromethylcyclohexanonc using classical chemistry, whereas 12 was built up by fragmentation of a perhydroazepinone, followed by an intramolecular Diels-Alder cyclization. While the process led to the unnatural ring junction (2b), the natural configuration (Za) was obtained by base catalysed epimerization of 4,5-epoxy-17-methyl-9-oxo-10-nor-14 alpha-morphinan 21. Copyright (C) 1996 Elsevier Science Ltd