Dichloroketene-induced cyclizations of vinyl sulfilimines: application of the method in the synthesis of (+/-)-desoxyeseroline.

Journal Article (Journal Article)

The reactions of several aryl-, furanyl-, and vinyl-substituted sulfilimines with dichloroketene proceeded at 25 degrees C to yield thioalkyl-substituted gamma-lactams. The overall process involves nucleophilic addition of the nitrogen atom of the sulfilimine onto the highly electrophilic dichloroketene to first generate a zwitterionic intermediate. A subsequent [3,3]-sigmatropic rearrangement is followed by intramolecular trapping of the Pummerer cation by the amido anion to furnish the observed gamma-lactam product. Incorporation of donor groups on the aromatic ring of the sulfonyl functionality had little effect when aryl-substituted sulfilimines were used but exhibited a major effect on the efficiency of the reaction with furanyl-substituted systems. The placement of an electron donor group (i.e., OMe) on the sulfonyl aryl group enhances the nucleophilicity of the amido anion contained within the sulfonium ion intermediate and facilitates the rate of the 3,3-sigmatropic rearrangement. Styryl-substituted sulfilimines cyclize in a stereospecific manner and produce a 3:2-mixture of gamma-lactams and the isomeric imino-lactone system. The heavily functionalized gamma-lactams are easily converted to a variety of nitrogen containing substrates. The vinyl sulfilimine cyclization method was applied to the total synthesis of the Calabar alkaloid (+/-)-desoxyeseroline.

Full Text

Duke Authors

Cited Authors

  • Padwa, A; Nara, S; Wang, Q

Published Date

  • October 2005

Published In

Volume / Issue

  • 70 / 21

Start / End Page

  • 8538 - 8549

PubMed ID

  • 16209605

Electronic International Standard Serial Number (EISSN)

  • 1520-6904

International Standard Serial Number (ISSN)

  • 0022-3263

Digital Object Identifier (DOI)

  • 10.1021/jo051550o


  • eng