光化学条件下(β-重氮-α,α-二氟乙基)膦酸酯与羧酸的酯化反应

Esterification of Carboxylic Acids with(β-Diazo-α,α-difluoroethyl)phosphonates under Photochemical Conditions

利用可见光促进的O-H插入反应可以在温和条件下实现羧酸与原位生成的(β-重氮-α,α-二氟乙基)膦酸酯的酯化反应,以良好的产率得到了含有α,α-二氟甲基膦酸酯的羧酸酯类化合物.该反应操作简单,对于不同的官能团具有良好的适应性.因此,这一反应为α,α-二氟甲基膦酸酯衍生物的合成提供了一种高效的策略.

Fluoroalkyl-substituted diazo compounds belong to one of the most powerful tools in organic synthetic chemistry and their transformations have attracted numerous attention.Since the reagent,trifluorodiazoethane,was discovered in 1943,it has attracted many research interests in organic synthesis.On the contrary,the similar difluorodiazoethane(CF2HCHN2),which just changes CF3 group to CF2H group,however,leads to significant changes on their chemical properties,in particular the stability.Until now,the studies on difluorinated diazo compounds remain less explored.Therefore,the related chemistry on difluorodiazoethane emerges as a hot research topic,and the inventory of methods for the preparation and application of new diazo compounds is continuously supplemented.In this communication,a visible-light-promoted esterification reaction of carboxylic acids with in situ generated(β-diazo-α,α-difluoroethyl)phosphonates via O-H insertion has been achieved under mild conditions,which affordedα,α-difluoromethyl phosphonates(DFMPs)-containing esters with good chemical yields.Several carboxylic acids and amines featuring various functional groups are well compatible in the reaction under photo-chemical conditions.A control experiment with the addition of D2O has been performed to verify the proton-transfer process involved in this reaction,and a possible mechanism containing in situ generation of diazo intermediate and protonation is provided.This reaction is operationally simple and shows good functional group compatibility providing an efficient and sustainable strategy for the assembly ofα,α-difluorinated phosphonate derivatives.A typical procedure for this visible-light-promoted reaction between(β-diazo-α,α-difluoroethyl)phosphonates and carboxylic acids is presented as follows:into a vail were taken amine 1(0.2 mmol),carboxylic acid 2(0.1 mmol),t-BuONO(0.24 mmol)and CHCl3(3 mL).The mixture was heated to 60℃and stirred in the presence of 4.5 W blue LEDs for 4 h.Then,solvent was removed in vacuum.Product 3 was purified by TLC plate of 20 cm×20 cm using petroleum ether/ethyl acetate(4∶1,V/V)as eluent.