Palladium-Catalyzed Dialkylation Of C-C Triple Bonds:Access To Multi-Functionalized Indenes

The difunctionalization of alkynes is a highly rapid and efficient strategy to access multi-substituted alkenyl moieties in organic synthesis.During the past several decades,an alternative strategy via nucleophilic cyclization to alkynyl triple bond for the con-struction of cyclic compounds has attracted continuous interest from organic chemists.Among them,1,3-dien-5-ynes have been extensively exploited as the starting materials for the synthesis of various carbo-and heterocycles due to their flexible reaction properties.So far,many transition-metal such as Au?Pt?Ru?Rh?Pd etc have been successfully applied as efficient catalysts for the synthesis of naphthalene and heterocyclic compounds via 6-endo-dig cyclization.To the best of our knowledge,indene derivatives have shown important pharmaceutical activities,for example,oxytocin antagonists,antiproliferative agents,estrogen receptor modulators,and h5-HT6 serotonin receptor.At the same time,the substituted indene derivatives widely used as building blocks for the synthesis of functional materials.Combining our previous works and literature reports,it was found that tuning the substituent locations on the alkenyl double bond of 1,3-dien-5-ynes would result in different cyclization pathways.Accordingly,we hypothesized that the multisubstituted indenyl products could be accessed via choosing suitable coupling partner to trap the vinylpalladium species generated in situ after 5-endo-dig cyclization of 1,3-dien-5-ynes.It is well known that the allylic alcohols are efficient and useful alkyl and allylic precursors in palladium-catalyzed coupling reactions.The main contents include the following two parts:Part ?:The development of the difunctionalization of alkynes.In this section,we systematically introduce intermolecular and intramolecular difunctionalization of alkynes.Among them,the intramolecular difunctionalization of alkynes is divided into the synthesis of heterocyclization/functionalization and carbocyclic compounds.Wherein the synthesis of carbocyclic compound according to the cyclization modes of 1,3-dien-5-ynes can be classified as 6-endo-dig cyclization,5-exo-dig cyclization and 5-endo-dig cyclization.Part ?:Palladium-catalyzed dialkylation of C-C triple bonds:access to multi-functionalized indenes.In this part,different palladium catalysts,copper salts and solvents were screened to optimize the palladium-catalyzed tandem dialkylation reactions of 1,3-dien-5-ynes for the synthesis of multisubstituted indene derivatives.Under the optimized reaction conditions,the substrate scope of 1,3-dien-5-yne derivatives was explored and the generality of different allylic alcohols as coupling partner was examined.The reaction has the following advantages:(1)the reaction utilizes inexpensive metal palladium as a catalyst;(2)mild reaction conditions?high reactivities and universalities;(3)one-pot method for tandem cyclization.