title: Conformational, steric and electronic effects on the site- and chemoselectivity of the metal-catalyzed reaction of N-bis(trimethylsilyl)methyl, N-(2-indolyl)methyl α-diazoamides.
abstract: The Rh(II)- and Cu(II)-catalyzed reactions of N-bis(trimethylsilyl)methyl, N-(2-indolyl)methyl α-diazoamides are investigated to delineate how conformational, steric and electronic factors influence the site- and chemoselectivity of the metallocarbenoid reaction. The N-bis(trimethylsilyl)methyl (N-BTMSM) group is found to be essential in promoting the metallocarbenoid reaction at the N-(2-indolyl)methyl moiety as well as providing subtle but effective conformational influence about the amide N-C(α) sigma bond in diazoamides carrying an N-C(α) alkoxymethyl side-chain, to afford excellent site- and chemoselectivity. In general, the metal-catalyzed reactions are found to favor metallocarbenoid addition to the indole C(2)-C(3) double bond over C-H insertion to give cyclopropanated products (tetracyclic γ-lactams); however, chemoselectivity is also affected by steric effects, as revealed in the N-[2-(3-methylindolyl)]methyl diazoamides, and to some extent by the nature of the catalyst employed, as seen in the N-C(α)-alkoxymethyl diazoamides. The tetracyclic γ-lactams are found to rearrange to give good to high yields of the tricyclic indole derivatives under the metallocarbenoid reaction conditions or under acidic conditions. The propensity of the tetracyclic γ-lactams to undergo rearrangement is found to be dependent on the nature of the α-substituent on the original diazo carbon and the indole N-substituent.
authors.affiliation: Department of Chemistry and Biochemistry, University of Regina, Regina, Saskatchewan, Canada S4S0A2.
authors.forename: Bao
authors.initials: B
authors.lastname: Zhang
authors.forename: Andrew G H
authors.initials: AG
authors.lastname: Wee
mesh_terms: D000577:Amides / Q000737:chemistry*; D001391:Azo Compounds / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D004583:Electrons; D007211:Indoles / Q000737:chemistry*; D008745:Methylation; D008958:Models, Molecular; D008968:Molecular Conformation; D012238:Rhodium / Q000737:chemistry*
chemical_list: D000577:Amides; D001391:Azo Compounds; D007211:Indoles; D003300:Copper; C030374:indole; D012238:Rhodium