Synthesis of medium-bridged twisted lactams via cation-pi control of the regiochemistry of the intramolecular Schmidt reaction.

ABSTRACT: Medium-bridged twisted amides can be synthesized by the intramolecular Schmidt reaction of 2-azidoalkyl ketones. In these reactions, the regiochemistry of the Schmidt reaction is diverted into a typically disfavored pathway by the presence of an aromatic group at the alpha-position adjacent to the ketone, which stabilizes the predominantly reactive conformation of the azidohydrin intermediate by engaging in a nonbonded cation-pi interaction with the positively charged diazonium cation. This results in the rarely observed rearrangement of the C-C bond distal to the azidoalkyl chain. This reaction pathway also requires the azide-containing tether to be situated in the axial orientation in the key azidohydrin intermediate. Examination of the effect of substitution of aromatic rings on the reg

SUBMITTER: Szostak M 

PROVIDER: S-EPMC2821462 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature