Asymmetric Phase-Transfer Catalyzed [3+2] Cycloaddition For Synthesis Of Cyclopentenes

Chiral five-membered all-carbon ring structures are widely existed in nature products and drug molecules,and have always been one of the core skeletons with high occurrence rate in small molecule drug development.Because the synthesis of five-membered all-carbon ring structures via[3+2]cycloaddition reactions has the obvious advantages of simplicity,high efficiency and high atomic economy,the construction of five-membered all-carbon ring structures with regioselectivity and stereoselectivity by[3+2]cycloaddition has received extensive attention.In recent decades,asymmetric[3+2]cycloaddition reactions catalyzed by chiral metal complexes and some small organic molecules have achieved remarkable results,but the construction of chiral five-membered all-carbon rings by asymmetric phase transfer catalyzed[3+2]cycloaddition has not been successful.In this thesis,the synthesis of cyclopentenes by asymmetric[3+2]cycloaddition under phase transfer catalysis were studied.In the first chapter of this thesis,the reactions of asymmetric[3+2]cycloaddition to construct chiral five-membered all-carbon ring structures were reviewed.It is mainly divided into asymmetric[3+2]cycloaddition reactions catalyzed by chiral metal complexes and small organic molecules.Among them,metal asymmetric catalysis mainly includes the reactions ofπ-allyl,cyclopropane,metal carbene,while the organic small molecule asymmetric catalysis includes the reactions of allenes,MBH derivatives,acroleins,cyclopropanes.It should be noted that there is only one report on the asymmetric phase transfer catalyzed[3+2]cycloaddition for synthesis of cyclopentene,but the enantioselectivity was very low.The second chapter mainly described the spiro skeleton-based chiral quaternary ammonium salts catalyzed[3+2]cycloaddition reactions for synthesis of cyclopentenes.The optimal conditions were selected by screening different bases,temperatures,solvents,and phase transfer catalysts.The optimal conditions for this reaction were determined as follows:10 mol%chiral quaternary ammonium salt 3t with side chain of 3,5-^tBu₂C₆H₃as catalyst,toluene as solvent,50%potassium hydroxide aqueous solution as base and-30°C.Under the optimal reaction conditions,the yield of the chiral cyclopentenes product were up to 92%,and the enantioselectivity were up to 81%.Then the scope of the substrate was studied.Forα,β-unsaturated ketones,the aryl,heteroaryl,alkyl substituents at R¹or R²position were compatible.Forα,β-unsaturated esters,the reaction is difficult to run.Theα,β-unsaturated aldehydes are decomposed under this reaction conditions.We speculated that the reaction mechanism may be through conjugated addition-conjugated addition-elimination domino processes to deliver cyclopentene products.