Oxidative rearrangement of indoles: a new approach to the EFHG-tetracyclic core of diazonamide A.

A new approach to the ring EFHG-tetracyclic core fragment of the marine secondary metabolite diazonamide A is described. The route is based on the oxidative rearrangement of 3-arylindole-2-carboxylates. Thus, a range of 3-arylindole-2-carboxylates (3, 8) underwent rearrangement to the corresponding 3,3-disubstituted oxindoles (4, 9) with migration of the ester group upon treatment with tert-butyl hypochlorite followed by acid. The oxindoles 9 with a 3-[2-(4-methoxybenzyloxy)]phenyl substituent underwent cyclization to the tetracyclic aminals 11 following N-protection, reduction, and treatment with methanesulfonic anhydride. The methodology was applied to the tyrosine-indole derivative 17 to give the EFHG-tetracyclic core of diazonamide A.