Study On Phosphine-catalyzed Cycloaddition And Addition Of Allenoates And Bioactivity Of Reaction Products

Phosphines are widely used as stoichiometric reagents or catalysts in organic synthesis. Their importance has been witnessed by several well-known name reactions such as the Wittig reaction for olefin formation, Staudinger reaction for formation of amines and derivatives, and Mitsunobu reaction, especially for the formation of esters. The significant potentialities of phosphines have further been exploited by applying them in the Michael, Morita-Baylis-Hillman, annulation and isomerization reactions et al. The reactions involving phosphines as reagents or catalysts can often be carried out under mild conditions, and are compatible with many different functional groups, providing a variety of useful molecules with a high degree of functionalization. Consequently, those reactions (and their enantioselective variants) have been widely applied in the synthesis of polyfunctionalized derivatives such as biologically active heterocycles and total synthesis of natural products.Recently, developing new reactions with phosphines as reagents or catalysts has attracted great attention. Activated allenes subjected to nucleophilic phosphine catalysis conditions exhibit superbly diverse reactivity toward electrophilic reagents. These allenes can function as one-, two-, three-, or four-carbon synthons when reacting with a variety of electrophilic coupling partners (including aldehydes, alkenes, imines, and aziridines) undergoing [2+1],[4+1],[3+2],[2+2+2],[3+3],[4+2],[4+3], or [8+2] annulations. The particular reactivity of the allene substrate is often induced by its electrophilic coupling partner. Consequently, the search for new electrophilic substrates exhibiting suitable reactivity for effective use in the synthesis of heterocycles with new skeletons or structural features is a major challenge for the formation of diverse cycloaddition products from the nucleophilic phosphine catalysis of allenes. In this context, we employed azomethine imines as a new type of electrophilic coupling reagent and accomplished the phosphine-catalyzed [3+N] annulations of azomethine imines with allenoates.In this dissertation we describe the phosphine-catalyzed [3+2], and [4+3] annulations of azomethine imines (1) and allenoates. Phosphine-catalyzed [3+2] and [4+3] annulation reactions of C,N-cyclic azomethine imines with allenoates have been developed to give a variety of pharmaceutically attractive tetrahydroisoquinoline derivatives in moderate to excellent yields. The two distinct reaction pathways,[3+2] and [4+3] cyclization, depend on the nature of nucleophilic phosphine and allenoate. Generally, for α-alkyl allenoates, the reactions always proceed with [3+2] cyclization as major pathway no matter what phosphine was used; for a-ArCH2-substittuted allenoates, the reaction pathway was controled by the phosphine catalyst used.In order to expand the scope of azomethine imines, the reaction of azomethine imine (5) with allenoate (2f) has also been designed and tried. Various reaction conditions have been examined, but the desired reaction did not work.In addition we describe the phosphine-catalyzed additions of5-phenylpyrazolidin-3-one (compound6) and allenoates. Some3-pyrazolone derivatives (compound7) are prepared.Since dinitrogen-fused heterocycles often display excellent bioactivities, the bioactivities of the cycloaddition reaction have also been studied. By the bioassay, although the products haven’t herbicidal and insecticidal activities, they demonstrate excellent bactericidal activities. Especially, two compounds displayed higher activities than the control pesticides. The facts demonstrate these compounds could be used as the lead compound for the further pesticide discovery.