In Situ Formation Of PhSCl And PhSeCl And Their Applications To Chalcogenation Of Enamines Under Transition-metal Free Conditions

Thioether is a very important structural framework,widely existing in drug molecules with biological activity and organic materials,which can also be used as a precursor of sulfide with higher oxidation state and participate in a series of chemical transformation,which has great research value.The formation of C-S bond is a key step in the construction of thioether compounds.The construction of traditional C-S bond is mainly a cross-coupling reaction involving transition metal.Due to its high price and difficulty in post-processing,its application is greatly limited.Besides,other non-metallic C-S bond building methods have some problems,such as harsh conditions,high toxicity and low atomic utilization.Nowadays the rapid development of green chemistry,environment-friendly,atomic economy,high efficiency and simplicity all put forward higher requirements for the construction method of C-S bond.Therefore,it is particularly important to explore new ways to build C-S bond.In this paper,we used a green and efficient oxidant and a sulfur source with low toxicity to interact with the enamine compounds under mild conditions to obtain the?-thioenamine compounds and achieve the construction of C-S bond.Firstly,the optimal conditions were selected by using?Z?-3-amino-3-phenyl methyl acrylate as the model substrate,diphenyl disulfide as the sulfur source.The reaction solvent was determined to be N,N-dimethyl formamide,the reaction temperature was determined to be room temperature,and the feeding ratio was determined to be 1:0.5:0.5.At the same time,the tolerances of different substituent substrates to this method were studied.The yield is higher when R¹ is aromatic ring,heteroaromatic ring and R² is ester group.When R¹ is an alkyl group and R² is a strongly electron absorbent group,the yield is lower than other groups.The method was extended to the preparation of?-selenized enylamines,with a lower yield than thioetherification,but providing a new path for the construction of C-Se bond.The sulfide etherification/selenium etherification products obtained by the reaction were confirmed by ¹H NMR,¹³C NMR and HRMS.