Synthesis of chiral oxacyclic dienes via ruthenium-catalyzed enyne metathesis: useful building blocks for chiral tricyclic oxygen derivatives

Various chiral oxacyclic dienes were synthesized via enyne metathesis using Grubbs catalyst (PCy3)2Cl2RuCHPh. A series of substrates bearing a 1,2-diol skeleton was prepared from (2S)-(benzyloxy)-propanal. The enyne metathesis proceeds smoothly in CH2Cl2 at 23°C with a low loading of catalyst (2.0 mol%) under ethylene gas (1–2.5 atm), giving good yields of products without epimerization at any stereogenic carbon. Heating compound comprising a disubstituted alkyne in benzene (80°C) under nitrogen resulted in formation of two diastereomers via epimerization of the primary product. The epimerization occurs at the oxacyclic carbon rather than the benzyl carbon. Diels–Alder reactions of chiral oxacyclic dienes and with maleic anhydride, maleimide and benzoquinone proceeded with high diastereoselectivities, yielding a single cycloadduct efficiently at ambient conditions. The structures of Diels–Alder adducts were determined by 1H NOE NMR spectra. The cycloadducts were formed via the approach of dienophiles to the diene in endo mode and opposite the substituent of the stereogenic center. The cycloadducts and were transformed into enantiopure tricyclic furans and after transformation of the (2S)-(silyloxy)ethyl group into an acetate group.