Control of Competing N−H Insertion and Wolff Rearrangement in Dirhodium(II)-Catalyzed Reactions of 3-Indolyl Diazoketoesters. Synthesis of a Potential Precursor to the Marine 5-(3-Indolyl)oxazole Martefragin A

Dirhodium(II)-catalyzed reaction of 3-indolyl α-diazo-β-ketoester 25 in the presence of hexanamide
results in competing metal carbene N−H insertion and Wolff rearrangement. The corresponding
phenyl diazoketoester 32, on the other hand, gives only the product of N−H insertion, suggesting
that the indole moiety is more prone to 1,2-rearrangement. The competing processes were
investigated in a range of 3-indolyl α-diazo-β-ketoesters (36, 38, 40, 44); these studies established
that the Wolff rearrangement could be effectively suppressed by the presence of a strong electron-withdrawing group on the indole nitrogen. Dirhodium(II) catalysts were also more effective than
copper or Lewis acid catalysts in favoring the insertion process. The products of N−H insertion,
the ketoamides (26, 47, 49, 51, 53), were readily cyclodehydrated to the corresponding 5-(3-indolyl)oxazoles. The N−H insertion/cyclodehydration methodology was used in a formal synthesis of the
marine natural product martefragin A. Thus the N-Boc homoisoleucine amide 23, prepared by
asymmetric hydrogenation of a dehydro amino acid, underwent N−H insertion with the rhodium
carbene derived from the N-nosyl indolyl diazoester 40, followed by cyclodehydration and
deprotection to give the 5-(3-indolyl)oxazole martefragin A precursor 75.