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

摘要

Dirhodium(II)-catalyzed reaction of 3-indolyl alpha-diazo-beta-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 alpha-diazo-beta-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.