Pd-catalyzed carbocyclization-Negishi cross-coupling cascade: a novel approach to 1alpha,25-dihydroxyvitamin D3 and analogues

Org Lett. 2005 Dec 22;7(26):5885-7. doi: 10.1021/ol052489c.

Abstract

[reaction: see text] A mild palladium-catalyzed cascade has been used for the synthesis of the hormone 1alpha,25-dihydroxyvitamin D3 (calcitriol, 1a) and its analogues 1b and 1c. This one-pot process involves two consecutive transformations at room temperature: An initial palladium-catalyzed 6-exo-cyclocarbopalladation of vinyl triflates followed by a Negishi cross-coupling reaction with an alkenyl zinc. This novel strategy opens new possibilities for the preparation of a variety of new vitamin D analogues of therapeutic potential, particularly with modifications at the triene and/or ring-A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Cyclization
  • Molecular Structure
  • Palladium / chemistry*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / chemical synthesis

Substances

  • dihydroxy-vitamin D3
  • Vitamin D
  • Palladium