Tandem Sakurai-aldol addition reactions as a route to structurally complex carbocycles

J Org Chem. 2005 May 27;70(11):4375-9. doi: 10.1021/jo050225y.

Abstract

Tandem intramolecular Sakurai-aldol reactions provide a concise and highly diastereoselective route to substituted cyclohexenone derivatives. The cyclization substrates are readily obtained using olefin isomerization-Claisen rearrangement (ICR) reactions to prepare the key chiral allyl silane precursors. The Claisen reaction products are elaborated to the chiral Sakurai-aldol substrates by an efficient two-step sequence involving vinyl organometallic-aldehyde addition and oxidation of the resulting alcohol. The reaction of the resulting enones with TiCl(4) elicits a highly stereoselective allyl silane conjugate addition to produce a trichlorotitanium enolate as the reaction intermediate; intermolecular trapping of the enolate with an aldehyde provides pentasubstituted cyclohexanone derivatives in which the annulation reaction establishes four stereocenters and two new C-C bonds. A fully intramolecular variant of the Sakurai-aldol reaction that creates four stereocenters, two new C-C bonds, and establishes two new carbocyclic rings is also described.

Publication types

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

MeSH terms

  • Alkenes / chemistry
  • Catalysis
  • Chemistry, Organic / methods*
  • Cyclization
  • Cyclohexanones / chemical synthesis*
  • Molecular Structure
  • Silanes / chemistry
  • Stereoisomerism
  • Titanium / chemistry

Substances

  • Alkenes
  • Cyclohexanones
  • Silanes
  • Titanium