title: 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.
abstract: 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.
authors: Department of Chemistry, University of Exeter, Stocker Road, Exeter, EX4 4QD, United Kingdom.
authors: James R
authors: JR
authors: Davies
authors: Peter D
authors: PD
authors: Kane
authors: Christopher J
authors: CJ
authors: Moody
authors: Alexandra M Z
authors: AM
authors: Slawin
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology; D000577:Amides / Q000737:chemistry; D000588:Amines / Q000737:chemistry*; D001391:Azo Compounds / Q000737:chemistry; D002384:Catalysis; D002413:Cations, Divalent; D004952:Esters / Q000737:chemistry; D006838:Hydrocarbons; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D008956:Models, Chemical; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: C503523:5-(3-indolyl)oxazole; D000470:Alkaloids; D000577:Amides; D000588:Amines; D001391:Azo Compounds; D002413:Cations, Divalent; D004952:Esters; D006838:Hydrocarbons; D007211:Indoles; C115837:Martefragin A; D010080:Oxazoles; C030011:carbene; C030374:indole; D012238:Rhodium; D008697:Methane