Tandem double-intramolecular [4+2]/[3+2] cycloadditions of nitroalkenes. Studies toward a total synthesis of daphnilactone B: piperidine ring construction

J Org Chem. 2006 Jan 20;71(2):593-605. doi: 10.1021/jo052001l.

Abstract

[reaction: see text] Two model studies in support of a total synthesis of the complex polycyclic alkaloid daphnilactone B have been completed. The objectives of the models studies were to demonstrate the use of a tandem double-intramolecular [4+2]/[3+2] nitroalkene cycloaddition for the stereocontrolled construction of four of the rings in the core of the natural product. The first model study established the ability to create a pyrrolidine ring corresponding to ring A of daphnilactone B through a modification of the dipolarophile and subsequent functional group manipulations. The second model study required the modification of the dienophile in the [4+2] cycloaddition to accommodate the formation of a piperidine ring (ring B of daphnilactone B). Nitroalkene 26 containing a diene as the dienophile served well in the tandem cycloaddition to afford the nitroso acetal 38a in 77% yield. Subsequent functional group manipulations allowed for the high-yielding conversion to the core of daphnilactone B.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis*
  • Alkaloids / chemistry*
  • Alkenes / chemical synthesis*
  • Alkenes / chemistry*
  • Lactones*
  • Models, Molecular
  • Molecular Conformation
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry*

Substances

  • Alkaloids
  • Alkenes
  • Lactones
  • Piperidines
  • daphnilactone B