title: The diazo route to diazonamide A. Studies on the indole bis-oxazole fragment.
abstract: [structure: see text] Various approaches to the indole bis-oxazole fragment of the marine secondary metabolite diazonamide A are described, all of which feature dirhodium(II)-catalyzed reactions of diazocarbonyl compounds in key steps. Thus, 3-bromophenylacetaldehyde is converted into an alpha-diazo-beta-ketoester, dirhodium(II)-catalyzed reaction of which with N-Boc-valinamide resulted in N-H insertion of the intermediate rhodium carbene to give a ketoamide that readily underwent cyclodehydration to give (S)-2-(1-tert-butoxycarbonylamino)-2-methylpropyl]-5-(3-bromobenzyl)oxazole-4-carboxamide, after ammonolysis of the initially formed ester. This aryl bromide was then coupled to a 3-formyl-indole-4-boronate under Pd catalysis to give the expected biaryl. Subsequent conversion of the aldehyde group into a second alpha-diazo-beta-ketoester gave a substrate for an intramolecular carbene N-H insertion, although attempts to effect this cyclization were unsuccessful. A second approach to an indole bis-oxazole involved an intermolecular rhodium carbene N-H insertion, followed by oxazole formation to give (S)-2-[1-tert-(butoxycarbonylamino)-2-methylpropyl]-5-methyloxazole-4-carboxamide. A further N-H insertion of this carboxmide with the rhodium carbene derived from ethyl 2-diazo-3-[1-(2-nitrobenzenesulfonyl)indol-3-yl]-3-oxopropanoate gave a ketoamide, cyclodehydration of which gave the desired indole bis-oxazole. Finally, the boronate formed from 4-bromotryptamine was coupled to another diazocarbonyl-derived oxazole to give the corresponding biaryl, deprotection and cyclization of which produced a macrocyclic indole-oxazole derivative. Subsequent oxidation and cyclodehydration incorporated the second oxazole and gave the macrocyclic indole bis-oxazole.
authors.affiliation: Department of Chemistry, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
authors.forename: James R
authors.initials: JR
authors.lastname: Davies
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kane
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Moody
mesh_terms: D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis*; D007211:Indoles; D010080:Oxazoles / Q000138:chemical synthesis*
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; D007211:Indoles; D010080:Oxazoles; C408862:diazonamide A