Tandem Sakurai-aldol addition reactions as a route to structurally complex carbocycles.
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.
Stevens
Benjamin D
BD
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Nelson
Scott G
SG
D000475:Alkenes / Q000737:chemistry; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D003500:Cyclization; D003512:Cyclohexanones / Q000138:chemical synthesis*; D015394:Molecular Structure; D012821:Silanes / Q000737:chemistry; D013237:Stereoisomerism; D014025:Titanium / Q000737:chemistry
D000475:Alkenes; D003512:Cyclohexanones; D012821:Silanes; D014025:Titanium