Enantioselective [4+1] Cycloadditions Of Diazo Isatin And Electron Enriched Diene

Optically enriched and highly functionalized cyclopentenone or cyclopentanone are versatile and indispensable structural frameworks in the synthesis of complicated molecules which are significant in drug discovery,natural product,and bioactive compound.Many efforts have been devoted to the rapid and efficient assembly of synthetically important compound,but the synthesis is still full of challenge.Therefore,many focuses have been devoted to the simple and efficient synthesis of cyclopentenone and cyclopentanone.The metal carbene formed by diazo can act as both a nucleophile in the reaction and as an electrophile.And metal carbene as an electrophilic reagent,mainly react with heteroatomic nucleophiles,rich electronic aromatic and others.Carbon atoms as nucleophiles directly reacting with metal carbenes are not common and the products are mostly racemic.In this study,Rhodium catalyzed enantioselective [4+1] cycloadditions of diazo compound and electron enriched dienes such as Danishefsky's diene are firstly described.The nucleophilic enolate carbon reacts with rhodium carbene followed by a sequential intramolecular conjugate addition and thereby affording the optically and highly structurally enriched cyclopentenone bearing an all carbon stereocentre in 99% yields and with up to 90% ee;the optical purity can be further increased to 99% ee after simple recrystallization from a mixed solvent of hexane and ethyl acetate,and the proposed mechanism has been conjectured.It provides a simple and efficient method to synthesise the chiral cyclopentanone through a simple derivation.All the products were characterized and the absolute configuration was determined by X-ray single crystal diffractometer.