Endo-oxacyclizations of polyepoxides: biomimetic synthesis of fused polycyclic ethers.
Boron trifluoride-etherate promotes the endo-selective oxacyclization of polyepoxides derived from various acyclic terpenoid polyalkenes, including geraniol, farnesol, and geranylgeraniol, providing an efficient and stereoselective synthesis of substituted oxepanes and fused polyoxepanes. The mechanism of the oxacyclization reaction probably involves intramolecular nucleophilic addition of epoxide oxygen to open another epoxide that is activated as an electrophile by the Lewis acid. These oxacyclizations proceed stereospecifically with inversion of configuration upon opening of each epoxide to provide trans-fused polycyclic products. The oxacyclization cascade is terminated by a tethered nucleophile, which may be the carbonyl oxygen of a ketone, ester, or carbonate, or a trisubstituted alkene. The best oxacyclization yields are generally observed with tert-butyl carbonate as the terminating nucleophile, although in some cases the oxacyclization products include formation of tert-butyl ethers as a minor product. The oxacyclization transformations described herein may mimic ring-forming steps in the biosynthesis of trans-syn-trans-fused polycyclic ether marine natural products.
McDonald
Frank E
FE
Department of Chemistry, Emory University, 1515 Pierce Drive, Atlanta, GA 30322, USA. fmcdona@emory.edu
Bravo
Fernando
F
Wang
Xia
X
Wei
Xudong
X
Toganoh
Motoki
M
Rodríguez
J Ramón
JR
Do
Bao
B
Neiwert
Wade A
WA
Hardcastle
Kenneth I
KI
D001685:Biological Factors / Q000096:biosynthesis; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D002855:Chromatography, Thin Layer; D003500:Cyclization; D004852:Epoxy Compounds / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D015394:Molecular Structure; D014961:X-Ray Diffraction
D001685:Biological Factors; D004852:Epoxy Compounds