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.
J Org Chem
; 70(15): 5840-51, 2005 Jul 22.
Article
in En
| MEDLINE
| ID: mdl-16018676
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxazoles
/
Rhodium
/
Alkaloids
/
Amines
/
Indoles
Language:
En
Journal:
J Org Chem
Year:
2005
Document type:
Article
Affiliation country: