Hypervalent Iodine-Induced [3+2] Cyclization Reaction Of Arylamines With Amides

Amide fragments are widely present in various functional materials and active molecules,and the functionalization of C-N bond conversion is of great significance for the efficient preparation of various amine drug molecules.In the past decades,this type of organic transformation has become one of the most interesting research directions,but oxidative cyclization involving amide bonds is rare,and more challenging and stable thioamide C-N bond derivatization studies are rarely reported.At the same time,arylthiazole and aryloxazole compounds are widely used in pharmaceutical synthesis and material applications,and the continuous development of efficient synthesis of such compounds has always been one of the important contents of synthetic chemists’research.Based on this background,a novel hypervalent iodine-induced twofold oxidation cyclization reaction of arylamine with amide was developed for the activation and transformation of inert amide bonds,and a series of arylthiazole and oxazole derivatives were synthesized with high chemical selectivity.In this paper,arylamine and N,N-dimethylthiocarboxamide were used as research objects to prepare C2-unsubstituted aryloxazole derivatives by I(V)under solvent-free conditions,in which the breaking of the inert C(S)-N bond was realized.Firstly,the conditions of the oxidant,temperature,reactant concentration of the reaction were optimized by the single-factor control experiment,and the optimal conditions of the reaction were determined.Subsequently,by investigating the substrates with different electron effects,the compatibility of the reaction with substrate functional groups was determined,and finally 26 cases of arylthiazole derivatives with diverse structures were obtained.Derivatization experiments showed that the reaction was compatible with active molecular fragments such as(DL)-Menthol and(-)-Borneol,showing the practicality of the method.Finally,the reaction mechanism was explored by radical scavenger experiment and synthesis of possible intermediates.This method successfully realized the breaking of inert C(S)-N bonds,which further enriched the synthesis strategy of arylthiazole derivatives.On the basis of the above,the synthesis of C2-N-substituted aryoxazole derivatives was induced by Ⅰ(Ⅲ)using arylamine and N-substituted formamide as substrates.Firstly,the reaction conditions were optimized by adjusting the oxidant,temperature,reactant concentration and other factors to determine the best conditions for the reaction.Subsequently,the compatibility of substrate functional groups with different electron effects and steric hindrance was investigated under optimal conditions,and it was found that the reaction was not only compatible with heterocyclic fragments such as thiophene and thianthracene,but also compatible with more sensitive alkenyl fragments,and finally 30 cases of aryloxazole derivatives with different structures could be obtained.At the same time,it was pleasantly surprised to find that the reaction could be efficiently converted in only 1 min,and the yield could reach 53%.This method successfully implemented the activation of C(O)-N bonds,which provided a new idea for the synthesis of aryloxazole derivatives.In conclusion,a new type of hypervalent iodine-induced cyclization reaction between arylamine and amide was developed in this paper,and a series of arylthiazole and oxazole derivatives were synthesized with high chemical selectivity.Based on the research in this paper,it’s expected that the range of substrates will continue to be broadened in the future to enhance the compatibility of the reaction.