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)(2)Cl2Ru=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 23degreesC 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 5 comprising a disubstituted alkyne in benzene (80degreesC) 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 19 and 22 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 H-1 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 29 and 31 were transformed into enantiopure tricyclic furans 35 and 38 after transformation of the (2S)-(silyloxy)ethyl group into an acetate group. (C) 2002 Elsevier Science Ltd. All rights reserved.