Applications Of Organic Silyl Reagents Catalyzed Alcohols In The Synthesis Of Ether,Thioether,and Realted Pharmaceutical Intermediates

Oxygen and sulfur elements play an important role in organic synthesis,biochemistry,materials,medicine,pesticides and other fields.At the same time,oxygenates and sulfur-containing compounds are often the key structures in organic and pharmaceutical intermediates,many compounds containing oxygen and sulfur have unique biological antibacterial activity and chemical properties.The construction of C-O bond and C-S bond is the most important in the synthesis of these compounds.So far,the reported methods include Williamson reaction,acid-mediated dehydration methods,transition metal-catalyzed reactions,transition metal-free aromatic nucleophilic substitution reactions,etc.Among them,transition metal-catalyzed dehydroalkylation has been widely reported.These methods are restricted by environmental pollution,difficult operation,low conversion rate,by-products and other problems,and do not have high practical application value.Organic silicides are very important organic compounds,which are widely used in organic synthesis,materials and chemical industry.Organosilicon group has many unique advantages in protecting functional groups,activating and improving stereoselectivity.There are few reports about organosilicon reagents involved in the catalysis,but there may be new discoveries in the study of the catalytic performance of organosilicon compounds.Organic compounds(such as element-hydrogen compound E-H)were activated in situ by using catalytic amount of organosilicon reagents R3SiX(X=H,halogen,other anions,etc.)to form organosilicon intermediaates E-SiR3 with high activity.In this paper,the development of a new method of organosilicon catalysis through the double in-situ activation of reactants by organosilicon reagent has a good scientific significance and application prospect,which is worth exploring.The details are as follows:1.S-alkylation of alcohols catalyzed by organic silicides in the synthesis of asymmetric thioethers was studied.The method uses trimethyl halosilane as catalyst,alcohols and thioalcohols as substrate,and does not need solvent.For some substrates,inert gas protection is needed to improve the yield.In addition,some substrates are active and can obtain better yield at lower temperature.Compared with the traditional synthesis method,this method does not need transition metals and additives,has mild conditions,simple operation and environmental friendliness.2.O-alkylation of alcohols catalyzed by organic silicides in the synthesis of symmetrical ethers was studied.The method uses trimethyl halosilane as catalyst and alcohol as substrate without inert gas protection and solvent.Compared with the traditional method,the method is simple to operate and economical and green.3.O-alkylation of alcohols catalyzed by organic silicides in the synthesis of asymmetric ethers was studied.The method takes trimethyl halosilane as catalyst,two different alcohols as the substrate,without inert gas protection and solvent.The reaction is characterized by high yield,good tolerance to substrates,mild conditions,easy operation and easy separation of products.