Construction Of Multifunctionalized Fused Polycyclic Aromatic Compounds Via Tetrayne Cyclization

Natural products,materials and drug molecules with a wide range of uses generally have multifunctional aromatic fused ring as the main structure.Challenging synthesis of target molecules requires innovative methods to construct aromatic ring skeleton quickly.As an active intermediate in organic synthesis,benzyne has been a hotspot in this research in recent years.The precursor compound containing benzene ring eliminate two ortho-groups under certain conditions to form an active intermediate,then captured by other reagent.Based on the previous study of our research group,several multifunctional aromatic compounds were constructed by cascade reaction with benzyne intermediates generated in situ by different types of linear nonconjugated polyalkynes through HDDA reaction(hexadehydro-Diels-Alder reaction).The main research contents including the following four parts: 1.Fused multifunctionalized bridged aromatic hydrocarbons from in situ generated arynes and anthracene derivativesD-A reaction plays an important role in the construction of cyclic compounds.A series of multifunctionalized bridged polycyclic aromatic compounds were synthesized by cyclization of carbon or nitrogen linked tetraynes and anthracene derivatives.The multifunctionalized bridged pentacyclic aromatic skeleton and quaternary carbon triptycene derivatives were obtained by controlling the substituent properties of anthracene through cycloaddition reaction of two different active sites without metal catalysis,under mild conditions and with good compatibility for substrates.The structure of the product indicates that the reaction has specific stereoselectivity.2.Synthesis of versatile dibenzothio[seleno]phenes via tetrayne cyclizationThe dibenzothio[seleno]phenes derivatives were synthesized by cyclization of carbon linked tetraynes with triphenylphosphine selenide and triphenylphosphine sulfide without metal catalysis.The reaction system has good compatibility for terminal alkyne with electron-withdrawing or electron-donating group,and speculated the plausible mechanism of the reaction by stepwise [2+2] cycloaddition,4 ? electronic ring opening,the intramolecular nucleophilic addition,carbon-phosphon bond break,the formation of the carbon-carbon bond,finally remove diphenylphosphine to generate target compounds with good regioselectivity and stereoselectivity.3.Construction of phenanthrene derivatives by intermolecular TDDA reaction induced by tetrayne cyclizationThe synthesis of phenanthrene derivatives by intermolecular TDDA reaction of benzyne generated by HDDA reaction and substituted phenylacetylene was studied.The reaction system has good compatibility for terminal alkyne with electron-withdrawing or electron-donating group and linked atoms of carbon or nitrogen,and speculated the plausible mechanism.The experimental results of substrate expansion showed that phenylacetylene containing electron-withdrawing substituents reacted with tetrayne to generate naphthalene derivatives by two-step cycloaddition.Further studies have shown that when the molar ratio of the reactants increases,only to form naphthalene derivatives.The reactions have good chemical selectivity and stereoselectivity,and provide a new way to synthesize naphthalene and phenanthrene derivatives from simple materials under mild conditions.4.Direct alkylation and carbonylation of in situ generated arynes via tetrayne cyclizationThe insertion reaction of arynes is an effective method to introduce two vicinal functional groups.The synthesis of o-alkyl benzoyl derivatives under metal-free catalysis by the insertion of tetraynes with various carbon nucleophiles was studied.We speculated the possible reaction mechanism by stepwise [2+2] cycloaddition,opening of four-membered ring,and finally by taking proton hydrogen in solvent or under the action of water.With the expansion experiment of the substrate,found that with the increase of steric hindrance of the ortho group of alkyne carbon on benzyne,the reaction tended to be hydroalkylated and penta-substituted aromatic compounds were generated.The products have specific regional selectivity and stereoselectivity due to the structure of tetrayne precursor.This arynne difunctionalization provides a new method for the preparation of multisubstituted aromatic compounds.All the new compounds had been characterized by IR,NMR and HRMS spectroscopy,structures of some of the products had been confirmed by X-ray single crystal structure analysis.