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Issue 23, 2012
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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

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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–Cα sigma bond in diazoamides carrying an N–Cα 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–Cα-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.

Graphical abstract: 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

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Publication details

The article was received on 13 Jan 2012, accepted on 16 Apr 2012 and first published on 17 Apr 2012


Article type: Paper
DOI: 10.1039/C2OB25103E
Citation: Org. Biomol. Chem., 2012,10, 4597-4608
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    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

    B. Zhang and A. G. H. Wee, Org. Biomol. Chem., 2012, 10, 4597
    DOI: 10.1039/C2OB25103E

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