Asymmetric Cycloaddition Of Vinylcyclopropanes Between Conjugated Unsaturated Imines And Enantioselective Synthesis Of (-)-1,13-Herbertenediol

Highly functionalized cyclopentane derivatives are aboundant in natural products as well as bioactive molecules and pharmaceuticals.Thus,the development of highly efficient methods for assemble of such molecules is highly desired.The most efficient approach for cyclopentane derivatives is cycloaddition.Vinyl cyclopropane dicarboxylate undergoes readily cycloaddition with electron deficient alkenes.However,the enantioselective cycloaddition of vinyl cyclopropane and conjugated unsaturated imines are still elusive.Regarding our previous investigation of the enantioselective cycloaddition of vinyl cyclopropane dicarboxylate and imines generated in situ from aryl sulphonated indoles,we surmised that conjugated unsaturated imines would be interesting because imine,alkene and conjugated system are all likely to undergo cycloaddition with vinyl cyclopropanes.Herein we disclosed an enantioselective[3+2]cycloaddition of vinyl cyclopropane and acyclic conjugated unsaturated imines.After a systematic investigation of reaction condition such as chiral ligands,solvents,catalyst loading,temperature and additives,the optimal condition was set as:the reaction was carried out at room temperature at 0.1 mmol scale using toluene?2 mL?as the solvent in the presence of 5 mol%of Pd₂?dba?₃ in combination with 10 mol%of chiral phosporamidte as the catalyst.Various acyclic conjugated unsaturated imines were tolerable affording the optically enriched cyclopentane derivatives in up to 97%yield and with up to 98%ee and up to 20:1 dr.The cycloaddition can be scaled up to gram scale without the erosion of yield or selectivities.All the absolute configuration of cycloadducts are determined by X-ray structure.We also described herein an enantioselective synthesis of?-?-1,13-Herbertenediol based our previous development of rhodium catalyzed enantioselective formal[4+1]cycloaddition of diazo aryl acetate and Danishesky dienes.?-?-1,13-Herbertenediol was obtained in 25%yield and 80%ee in 11 steps.