Macrolactonization via Ti(IV)-mediated epoxy-acid coupling: a total synthesis of (-)-dactylolide [and zampanolide].
A total synthesis of dactylolide (1) is described. The key feature involves the Ti(IV)-mediated coupling of structurally complex "Sharpless epoxides" and carboxylic acids in either an intramolecular (macrolactonization) or an intermolecular mode. Other notable aspects include a proton-catalyzed, cis-selective construction of the 4-methylenetetrahydropyran ring; a selective oxidation of an allylic alcohol in the presence of a 1,2-diol by an oxoammonium ion; an efficient ring-closing metathesis reaction of an in situ (bis-TMS) protected alpha,omega-diene-vic-diol; and an aluminum-mediated aza-aldol reaction of a primary amide to 1 to construct the acyclic carbinolamide in zampanolide.
Hoye
Thomas R
TR
Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, USA. hoye@chem.umn.edu
Hu
Min
M
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis*; D007783:Lactones / Q000138:chemical synthesis*; D018942:Macrolides / Q000138:chemical synthesis*; D011161:Porifera / Q000737:chemistry; D013237:Stereoisomerism
D019086:Bridged Bicyclo Compounds, Heterocyclic; D007783:Lactones; D018942:Macrolides; C451487:dactylolide; C444900:zampanolide