Controlled Phosphorylation Of Thioesters: Reductive Coupling Vs Decarbonylative Coupling

Thioester is a kind of important bioactive functional compounds,which occurs in many natural products and synthetic compounds.The study on the activation and transformation of thioester has important reference value for the modification and modification of related functional molecules.However,there are few reports on the conversion of thioesters,which might be attributed to two points:1)the thioester is a conjugated structure,which increases the difficulty to activate thioester C-S bond;2)the sulfur atom can easily coordinate to metals,thus poisoning metal catalyst and reducing the reactivity.In the manuscript,we reported a controlled phosphorylation of thioesters with P（O）-H compound.By tuning the reaction conditions,thioester C-S bonds could be selectively transformed into sp²C-P bonds or sp³ C-P bonds.The specific research contents and results are as follows:（1）Catalyzed by PdCl₂,P（O）-H compound could quickly couple with thioesters through decarbonyl coupling,producing the corresponding aryl phosphine oxides.The reaction could complete in 20 minutes.The subdtrate scope is general.Thioesters with electron donating groups,halogens and heterocycles could effectively react with diphenylphosphine oxide.Under the reaction conditions,electron-deficient thioesters showed low reactivity.It should be noted that three kinds of P（O）-H compounds,i.e.secondary phosphine oxides,H-phosphinates and H-phosphonates,all were applicable to this reaction,efficiently coupling with thioesters to produce the corresponding aryl phosphoryl compounds.（2）With the use of K₂CO₃ as a base and Na H₂PO₂ as a reductant,P（O）-H compounds could react with thioesters through reductive coupling under the metal-free reaction conditions,generating the corresponding benzyl phosphoryl compounds.The reaction showed high functional group tolerance,i.e.tert butyl,phenyl,F,Cl,Br,trifluoromethyl,cyano,etc.,all were well compatible under the current reaction conditions.In addition,moderate to good yields were obtained when the thioesters bearing heterocycles were used.