Study On The Synthesis Of Benzo[c][1,2] Diazepines Via Rh-catalyzed[4+3] Annulation Of Pyrazolidinones And Propargylic Acetates

Recently,the combination of C-H functionalization and annulation with various unsaturated reactants has been recognized as a valuable strategy for the efficient construction of carbocyclic or heterocyclic compounds.Constructing five-and six-membered rings via C–H bond activation are copious through this strategy.However,access to medium-sized?seven-and eight-membered?rings is challenging because of the unfavorable entropic factors and transannular interactions.These combined factors?unfavorable entropic factors and transannular interactions?usually result in oligomerization or polymerization rather than cyclization.However,the synthesis of seven-membered rings is highly desirable,because seven-membered N-heterocycles are often endowed with significant biological and pharmaceutical activities.Typical methods for building these core structures generally rely on radical mediated reaction,palladium-catalyzed cross-couplings and ring-closing metathesis?RCM?.Each of these methods has its own limitations,such as the requirement of harsh conditions and/or poor functional group tolerance,or poorly accessible starting materials,or poor regioselectivity.Very recently,seven-membered nitrogen-containing heterocyclic rings have indeed been documented to be formed through[3+2+2],[4+3],[5+2]and[6+1]cycloaddition reactions.Great progress has been made in the construction of mononitrogen-containing seven-membered rings.The synthesis of seven-membered heterocycles containing multiple nitrogen??2?atoms has been rarely reported.Therefore,the reliable and practical methods for the efficient synthesis of structurally diversified seven-membered nitrogen heterocycles remains highly desirable.In this thesis,we have developed a rhodium-catalyzed C-H bond activation/cyclization reaction to construct structurally diversified seven-membered dinitrogen-fused heterocycles?Scheme 1?.The simple and easily available pyrazolinones and propargyl acetates are used as substrates.The corresponding seven-membered dinitrogen-fused heterocycles are obtained in moderate to good yields.N-Aryl-pyrazolidinones are easily accessible substrates which have been employed as four-atom synthons in this cyclization reaction.And the substrates with strong electron-withdrawing nitro and cyano group could also participate in the reaction smoothly,which provides chance for further modification of the products.In this reaction,propargylic acetates are employed as a C₃ synthon,in contrast to the usual C₁ or C₂ synthon behavior of related propargylic substrates.The catalytic system is simlple,avoiding external oxidant and ligand.The only additive used is sodium acetate,which is cheap and easy to obtain.Large scope of the functional groups are tolerated well and the yield of the amplification reaction is almost the same.In this reaction,the nitrogen-containing structure of the substrate itself is used as the directing group,and is cleverly incorporated into the target products through the final cyclization process,which greatly improves the atom and step economy.Moreover,the seven-membered dinitrogen-fused products are promising herbicides,carboxylase inhibitors and cancer inhibitors.In addition,the reaction mechanism was proposed based on the control experiments and DFT calculations?Scheme 2?.