Studies On Phosphine-mediated Cascade Cyclization Reactions Involving Dialkyl Azodicarboxylate Or MBH Carbonate With ?,?-unsaturated Ketones

Over the past decades,the phosphine-mediated annulation has developed as one of the most powerful tools for the synthesis of a wide array of synthetically useful or biologically important carbocyclic and heterocyclic compounds.These cyclic compounds are widely applied in the synthesis of pesticides,pharmaceuticals,fine chemicals and natural products.According to the difference of the amount of organophosphorus reagent,the reaction is usually divided into two categories:"phosphine-catalyzed"and"equivalent phosphine-promoted".In this dissertation,the synthesis of three kinds of novel nitrogen-containing heterocyclic compounds has been successfully realized by the domino cyclization reaction of dialkyl azodicarboxylate or Morita-Baylis-Hillman?MBH?carbonate with the?,?-unsaturate ketones promoted by tertiary phosphines.The dissertation is divided into the following four parts:Phosphine-mediated domino annulation reactions involving dialkylazodicarbo-xylate or MBH derivatives have constructed lots of useful carbon-and heterocycles.We have summarized the progress in phosphine-mediated reactions which allenoates were participated in detail in chapter one,which laid a solid foundation for the successful development of the research.In the second part,a cascade aza-Michael/Aldol annulation of 2-arylideneindane1,3-diones with in situ generated Huisgen zwitterions has been developed.This reaction afforded the desired products in moderate to good yields with excellent chemo-and diastereoselectivity.This strategy allows facile diastereoselective preparation of biologically important indenopyrazoline derivatives containing two contiguous chiral centers including a quaternary stereogenic center.Even in the gram scale amplification experiment,the yield of the target product and the diastereoselect-ivity is still retained.Finally,based on the experimental results of control experiments and ³¹P NMR spectroscopy,a possible mechanism is proposed for the reaction.The third part,through the design modification of the substrate and the system optimization of the reaction conditions,we found that the chemical selectivity of the reaction can be regulated by changing the?-substituent of chalcones,leading to efficient synthesis of multisubstituted pyrazoline derivatives in moderate to good yields with excellent chemoselectivity.This reaction represents a rare annulation reaction and accordingly reveals the new protocol to construct highly functionalized pyrazoline derivatives.Moreover,this is the first time,to the best of our knowledge,to achieve solvent-free synthesis based on Huisgen zwitterions.Further studies on these biologically active compounds are currently underway in our laboratory and will be reported in due course.The fourth part studies the[2+2+1]annulation reaction of unsubstituted Morita-Baylis-Hillman?MBH?carbonates with N-phenylpyrazolone derivatives catal-yzed by tertiary phosphines.This protocol proceeded well under mild conditions to furnish a series of spiro[cyclopentene-3,3'-pyrazole]derivatives containing five contiguous stereocenters and multiple functional groups,and the reaction afforded the desired products in moderate to highyields with good to excellent diastereoselectivities?up to 20:1?.A plausible reaction mechanism has also been proposed based on previous literatures.Efforts are in progress toward the development of asymmetric version of this reaction and in the application of this new methodology to synthesize interesting biologically active compounds.