Enantioselective Multicomponent Synthesis of Fused 6-5 Bicyclic 2-Butenolides by a Cascade Heterobicyclisation Process

The successive coupling of an alkoxy(aryl/heteroaryl)carbene complex of chromium with either a ketone or an imide lithium enolate and then a 3-substituted (H, TMS, PhCH2, PhCH2CH2, Me) propargylic organomagnesium reagent has afforded novel hydroxy-substituted bicyclic [4.3.0]-?-alkylidene-2-butenolides with three modular points that has allowed the efficient introduction of molecular complexity, including a homopropargylic alcohol core. The selective formation of these five- or six-component heterobicyclisation products is the result of the regioselective integration of the Grignard reagent as a propargyl fragment followed by a cascade CO/alkyne/CO insertion, ketene trapping and elimination sequence. By using lithium enolates of chiral N-acetyl-2-oxazolidinones and the corresponding propargylic organocerium reagents, both enantiomers of these bicyclic heterocycles were efficiently prepared with very high enantiomeric purity. Architecturally, these fused bicyclic butenolides are characterised by a highly unsaturated and oxygenated core and they exhibit strong blue fluorescence in solution.