Oxidative C-H Alkynylation Of 3,6-Dihydro-2H-pyrans

Objectives: Compounds having a skeleton of ?-substituted 3,6-dihydro-2H-pyran are widely present in people's lives and are structural motifs common in many biologically active natural products and synthetic drugs.Therefore,the rapid and efficient availability of such compounds is of great significance to us.A number of methods have been established to obtain ?-substituted 3,6-dihydro-2H-pyran skeletons with different substitution patterns,and the synthesis of ?-substituted 3,6-dihydro-2H-pyrans mainly depends on functional groups.Transformation,therefore,direct manipulation of a large number of readily available alpha-substituted 3,6-dihydro-2H-pyran backbones by structural core diversification strategies represents an attractive alternative to conventional oxygen-heterocyclic construction strategies.However,this solution still requires pre-installation of functional groups to get the desired product.So considering the economics of the steps and the economics of the atom,researchers are still exploring efficient and fast ways to synthesize such compounds.In recent years,C-H functionalization has attracted wide attention from researchers with minimal amount of intermediate functionalization and high atomic economy,namely,C-C bonds,C-O bonds,and C-N bonds have been constructed by C-H bonds.They used such reactions to modify the compounds,making this method a fast development.Researchers have also used this method for the functionalization of 3,6-dihydro-2H-pyran.Despite great innovations,these studies are still subject to toxic organotin,limited 3,6-dihydro-2H.-the effect of pyran range and alpha-substituent mode or expensive oxidizing agents.Alkynes,on the other hand,are common structural elements in the fields of biology,chemistry,materials science and medicine,and are valuable components due to their multiple chemical reactivity.Considering the importance of 2,4-disubstituted 3,6-dihydro-2H-pyran in pharmaceutical science,the use of readily available oxidizing agents for 4-substituted 3,6-dihydro-2H-pyrans for C-H alkynyl groups Systematic research will be a very attractive project.Methods: This paper mainly develops a direct and practical alkynylation and alkenylation of a 3,6-dihydro-2H-pyran skeleton with a series of potassium trifluoroborate by oxidation of a C-H bond.The use of various 3,6-dihydro-2H-pyrans is well tolerated by metal-free processes and rapidly provides 2,4-disubstituted 3,6-dihydro-2H-pyrans with different alpha-functional modes library.The specific work is as follows:Results: By optimizing the reaction conditions,2,3-dichloro-5,6-dicyano-1,4-benzoquinone(DDQ)acts as a strong oxidizing agent to promote C-H functionalization of the benzyl ether.The C-H alkynylation of 4-phenyl substituted 3,6-dihydro-2H-pyran and potassium trifluoroborate is selected to effect the reaction under DDQ oxidation.It is a pleasure to react in a dichloroethane(DCE)solvent at room temperature for three hours to give the desired,high yield alkynyl compound.After determining the reaction conditions,we extended the substrate of the different substituted 3,6-dihydro-2H-pyran and found that the aryl group is either an electron donating group or an electron withdrawing group,and the corresponding potassium trifluoroborate reagent.It can react very well at room temperature with a yield of up to 80%.The heterocyclic ring at the C4 position and the spiro ring at the ? position are also well tolerated.Subsequently,we studied the substrate range of potassium trifluoroborate,heteroaryl acetylene is an effective component of the method,alkyl acetylene proved to be a suitable component,and acetylene with benzyl ether is also well tolerated,a good reaction yield can be obtained.In addition to alkynylation,the 3,6-dihydro-2H-pyrans and styrene boronates also give good dilute products under standard oxidation conditions.We then derivatized with the alkynylated 3,6-dihydro-2H-pyran product obtained,all of which gave the desired product.Conclusion: An efficient and practical method for the preparation of ?-substitute DHPs is described.Under DDQ-mediated mild metal-free conditions,diverse 3,6-dihydro-2H-pyran undergo oxidative C–H alkynylation and alkenylation with a range of potassium trifluoroborates smoothly,rapidly providing a library of 2,4-disubstituted 3,6-dihydro-2H-pyran with diverse patterns of ?-functionalities for further diversification and bioactive small molecule identification.