Metal-free Mediated Reactions Based On Diazonium Salts

The diazonium salts have been widely used in organic synthesis because of its easy-preparation and high reactivity, it can be obtained by the reaction of anilines and nitrosating reagents. Diazonium salts are prone to undergo a homolytic dediazoniation to provide aryl radicals, various reactions based on the in-situ generated aryl radical from diazonium salts have been established, such as Sandmeyer-type reactions and Meerwein-type reactions. Transition-metals or photocatalysts are usually used in this kind of reaction since the transformation of diazonium salts to aryl radical go through a single electron transfer (SET) process. Metal contamination is a serious issue in the pharmaceutical industry, the use of transition-metals or photocatalysts restricts the application of diazounium salts. Meanwhile, the reactions need to use pre-prepared diazonium salts as starting material in most cases. Under this background, our research has been focused on metal-free mediated radical reactions based on in-situ generated diazonium salts. The results include:Addition and cyclization of N-arylacrylamides with in-situ generated diazonium salts: the diazonium salts can be generated by the reaction of anilines and tert-butyl nitrite. In the presence of BPO, the in-situ generated diazonium salts can react with N-Arylacrylamides to provide 3,3-disubstituted oxindoles. Using different kinds of anilines and N-Arylacrylamides, various 3,3-disubstituted oxindoles are synthesized. The chloro-and bromo-groups can be tolerated in this reaction and allows for further functionalization. Based on control experiment, we proposed a prossible radical mechanism.Cyanomethylation of alkenes with C-H bond activation of acetonitrile:in-situ generated diazonium salts as radical promoter:the in-situ generated diazonium salt from p-methoxyaniline and tert-butyl nitrite is used as radical promoter. The cyanomethylation and cyclization of N-Arylacrylamides with C-H bond activation of acetonitrile is realized. Based on control experiment, we proposed a possible radical mechanism. Meanwhiles, the in-situ generated diazonium salt can also be used as promoter for the C-H bond activation of CH2CI2 and CHCl3.A radical cascade arylation/aryl migration/desulfonylation of conjugated alkenes:in the presence of TBAI, the in-situ generated diazonium salts from anilines and tert-butyl nitrite can provide aryl radicals. The in-situ generated aryl radical can react with the C=C bond of N-phenyl-N-(phenylsulfonyl)methacrylamide, followed by the 5-ipso-cyclization and rapid desulfonylation, a-all-carbon quaternary stereocenters amides can be obtained. Through the deuterated experiment, we speculate that some H atom in the final product may come from the nitromethane.