Application Of Sulfuryl Fluoride In Cascade Organic Synthesis

Sulfuryl fluoride(SO2F2)has been known and used as a fumigant for over 50 years.Interestingly,only very recently it has gained widespread interest as a reagent for organic synthesis.Herein we focus on the organic synthesis involving sulfuryl fluoride promoted alcohol and phenol transformation.In the first part,we have developed a novel alkylation method for 1,3-dicarbonyl compounds that involves only bubbling SO2F2 through a solution of 1,3-dicarbonyl compound with NaOH and the necessary alcohol.This method is effective for both 1,3-diketones and beta-ketoesters.This method enabled methylation of 1,3-dicarbonyl compounds in good yield.It is also effective for alcohols with longer carbon chains,such as ethanol,isopropanol,n-butanol,and trifluoroethanol.The reaction also showed good tolerance to other functional groups.Compared with other known alkylation methods of 1,3-dicarbonyl compounds,this reaction is carried out in a relatively mild and safe condition.In the second part,we prepared Pd(OAc)2·Et3N reagent to simplify the experimental procedure using catalytic solid Pd(OAc)2..This reagent not only can efficiently catalyze the Suzuki-Miyaura coupling reaction of fluorosulfate,but also demonstrated the ability to catalyze Heck coupling and Sonogashira coupling.Applying this reagent and 2,4-dihydroxybenzoic acid as a raw material in the participation of SO2F2,we have achieved a one-pot synthesis of the drug diflunisal,with an isolation yield of 92%.