Trityl Ion Mediated C-H Functionalization Of Tetrahydrofurans And Dihydropyrans

?-substituted tetrahydrofurans and dihydropyrans skeletons are widely present in bioactive natural products and synthetic drugs.How to efficiently synthesize these compounds has attracted great attention of organic chemists in the world.Efficient methods have been reported,though requiring multiple steps and the installation of functional groups in advance.Therefore,developments of simple and efficient way to synthesize such compounds are required.In recent years,C-H activation has achieved rapid developments because of its simple operation,high atomic efficiency and in accordance with the goal of green chemistry.Many research groups have developed various oxidation systems to realizethe C-H functionalization of ethers,such as DDQ,TBHP,persulfate,T+BF4-and so on,with a lot of limitations though.Most of the substrates are limited to benzylic ether compounds,with less reports about tetrahydrofurans and dihydropyrans.The reaction conditions are harsh and each oxidation system can only be applied to a specific type of nucleophile.Therefore,we studiedthe use of trityl ion as oxidant torealize the C-H functionalization of tetrahydrofuran and unsymmetric cyclic ether..The C-H functionalization of tetrahydrofuran with potassium alkynyl trifluoroborate was selected as the model reaction for reaction conditions optimization,including the source of trityl ion,Lewis acid,temperature and solvent.With the optimized conditions in hand,the scope of different types of potassiumtrifluoroborates was investigated.The C-H functionalization of dihydropyrans was next studied.As for unsymmetrical substrates,the regio-and diastereoselectivity of the coupling reactions was foundexcellent as a result.Using phenylethylene as a nucleophile,the CDC reaction of tetrahydrofuran can also be achieved after a one-pot operation with two steps.The intermolecular and intramolecular KIE experiments were conducted after which possible reaction mechanism was suggested.In summary,we have successfully achieved the synthetic method for direct constructionof diverse a-functionalized tetrahydrofurans and unsymmetrical cyclic ethers using readily available tritylion as the oxidant.The reaction proceeds under mild conditions,exhibits good functional-group tolerance and excellent regio-and diastereoselectivity forthe unsymmetrical ethers.The method is efficient and practical,not only provides a straightforward way to synthesize complex molecules with biological activity,but also allowfacile and rapid accessto build up compound library by a structural-corediversificationstrategy.