Fe₂O₃-catalyzed Pummerer Rearrangement Of Acyl Chorides And Sulfoxides

Sulfur-containing organic compounds have been attracting more and more interest due to their essential role in the fields of drug design and discovery,material science etc.The a-acyloxy sulfides which were also called alkylthiomethyl esters could act as one of the most important carboxyl protecting groups according to its property.The drug molecules that contain alkylthiomethyl esters groups have been more easily absorbable.Furthermore,a-acyloxy sulfides also act as the flavor additives.So thea-acyloxy sulfides compounds could have a broad prospect in many science fields.The development of new methods for highly efficient preparation of the a-acyloxy sulfides has the important research value.Currently,the methods of preparation of the a-acyloxy sulfides include Pummerer rearrangement reaction,nucleophilic substitution,anti-Markovnikov addition,etc.Due to the simple construction of reactant and the economical efficiency,the Pumnerer reaction has been widely concerned.Because of the harsh traditional reaction conditions of the Pummerer reaction,it is very important to develop a new mild and rapid method reaction condition to prepare the a-acyloxy sulfides by the Pummerer rearrangement.In this study,we disclose here a method for the iron-catalyzed Pummerer rearrangement of acyl chlorides,sulfoxides and bases,providing a facile route for the synthesis of alkylthiomethyl ester.And 23 new compounds containing MTM esters were obtained with high yield up to 93%.Notably,a wide range of substrates could be suitable for the new method with high yields including the substrates bearing the electron-donating or electron-withdrawing groups,and some phenyl or aliphatic substrates.After the optimization of the reaction conditions,a new mild methods for the preparation of a-acyloxy sulfides had been developed.In this condition,the acyl chlorides act as nucleophile and the Et3N act as acid-binding agent.Under the catalysis of the cheap iron oxide(Fe2O3)with the toluene as solvent,the sulfoxides can be activated to produce the thionium ion intermediates,and then the nucleophiles attacked the ions at room temperature.The final product a-acyloxy sulfides can be obtained with satisfactory yields.Moreover,excellent yield can be achieved on a gram-scale,which showed the huge industry potential value of this new method in the future.Finally,we based on the traditional Pummerer rearrangement reaction mechanism,a new mechanism involving the Fe2O3-catalyst and mild condition was proposed.