Selective Sulfonylation And Acylation Of Carbohydrates Catalyzed By Ferric Chloride

The selective protection strategy can realize the site-selective functionalization of hydroxyl groups,and plays an important role in the efficient synthesis of sugar blocks and oligosaccharides.Among the many types of protecting groups that have been developed,acyl groups have become one of the most commonly used protecting groups in the synthesis of oligosaccharides due to the convenience of introduction and removal.Research on selective acylation methods has also been the focus of sugar chemists.In addition to the selective protection strategy,in the actual synthesis of sugar blocks and oligosaccharides,specific groups often need to selectively modify carbohydrate hydroxyl groups.Sulfonyl,as a special type of acyl,is often used in the selective modification of carbohydrate hydroxyl groups.In the broad field of organic chemistry including carbohydrate chemistry,the sulfonylated products are widely used as precursors for the synthesis of various biologically significant compounds and new functional materials.However,due to the low activity of sulfonyl(especially p-toluenesulfonyl),highly efficient methods are rare in the selective sulfonylation strategies that have been developed.It is mainly achieved by organotin and organoboron methods.The potential toxicity of organotin reagents is its biggest drawback,and the expensive price of organoboron also limits its application.Therefore,the development of a green,efficient and universal site-selective sulfonylation strategy remains a challenge in carbohydrate chemistry.Here,we have conducted a series of investigations to develop a catalytic system that can achieve both selective sulfonylation and selective acylation of substrates containing two or more hydroxyl groups,which is to combine a catalytic amount of Fe Cl₃with the ligand benzoyltrifluoropyruvate(Hbtfa)(Fe Cl₃/Hbtfa=1/2)in the presence of diisopropylethylamine(DIPEA)or potassium carbonate(K₂CO₃).The catalytic system exhibits high catalytic activity,leading to sulfonylated/acylated products with high site-selectivity and excellent isolated yield.It has a wide range of substrates,including glycosides containing cis-diol structure as well as simple 1,2-diols and1,3-diols.The reaction conditions of the system are mild,and the reaction is carried out at room temperature without the need for a strict water and oxygen removal process,which is easy to operate.The mechanism study shows that under basic conditions,Fe Cl₃first forms[Fe(btfa)₃]with twice Hbtfa(btfa=benzoyl trifluoropyruvate)in acetonitrile solution,and then Fe(btfa)₃and the two hydroxyl groups of the substrate form a five-or six-membered ring intermediate,and simultaneously release a molecule of Hbtfa.The subsequent reaction of the cyclic intermediate and the sulfonylating/acylating reagent results in selective sulfonylation/acylation of the substrate.The released Hbtfa will be combined with excess Fe Cl₃to form[Fe(btfa)₃]again to continue the catalytic reaction.This study captured all key intermediates through HRMS analysis,demonstrating this mechanism for the first time.