Radical-mediated Alkene Aminochlorination And Aromatic C-H Thiolation Reactions

Organic synthesis methodology plays a very important role in organic chemistry,which promotes the development of chemistry field and other relative academic subjects by providing new ideas and routines for synthesis.Recent years,radical reactions attract more attention than before.Partly because of its high efficiency,partly because of its characteristics are so different from that of ion reactions.In detail,radical reactions can form compounds that are less thermodynamically stable,can produce compounds with sterically crowded carbon atoms and can always be proceeded in mild reaction conditions.In addition,radical additions and cyclization reactions usually are not plagued by the competition from beta fragmentation,this certain property contributes a lot to the applicability of radical reactions.Hence,introducing radical reaction mechanism into the synthesis of aminochlorides means more than the work itself.Compounds like aminochlorides widely exist in living organisms and are rich in biological activities,also they can be versatile intermediates in organic synthesis.Methods that used to synthesize aminochlorides often contain metals,or use quantities of oxidants,or have big limitations in substrate scope.Therefore,it is of great necessity to develop a new simple,efficient and general method to synthesize aminochlorides.Thus,a general method for generating nitrogen-centered radicals has been developed,namely a radical aminochlorination reaction promoted by CuCl2.(1)By using compound a as the standard substrate(as shown in Scheme One),many variables and their amounts have been investigated systematically and thoroughly to assure their impact on the cyclization reaction.Based on these abundant experiments,the optimal reaction condition has been picked out finally.(2)The new method developed applies to many kinds of nitrogen-containing substrates,including variable active alkenes and different aryl ring substitutes.(3)The radical reaction mechanism was fully proved by the radical clock reaction.Also the applications of the reaction products were briefly illustrated.Scheme OneAfter the completion of the project above,we switched our attention to generating heteroatom radicals via electrochemical procedure,which is more environmental friendly,and how to make heteroatom radicals undergo intramolecular cyclization reactions to synthesize compounds of bioactivities and pharmaceutiacal usages.Benzothiazoles and thiazolopyridines are prevalent in pharmaceuticals and organic materials.Thus we reported a metal-,and reagent-free method for the synthesis of benzothiazoles and thiazolopyridines through 2,2,6,6-tetramethylpiperidine-N-oxyl radical(TEMPO)-catalyzed electrolytic C-H thiolation(see Scheme Two).This dehydrogenative coupling process provided access to a host of benzothiazoles and thiazolopyridines from N-(hetero)-arylthioamides.Mechanistic studies suggested that the thioamide substrates were oxidized with the electrochemically generated TEMPO+through an inner-sphere electron transfer to afford the corresponding thioamidyl radicals.The thioamidyl radical then underwent homolytic aromatic substitution to form the key C-S bond.