Sliver/Copper-catalyzed Direct Oxyphosphorylation Of Alkynes With H-phosphonates And Oxygen In The Air

β-ketophosphonates are extremely versatile intermediates in organic chemistry, especially for the construction of α,β-unsaturated carbonyl compounds through the well-known Horner-Wadsworth-Emmons(HWE) reactions. β-ketophosphonates exhibit a wide range of biological activities and outstanding metal-complexing abilities. β-ketophosphonates can therefore be used for liquid-liquid extraction of metal ions. In addition, β-ketophosphonates can serve as useful precursors in the synthesis of chiral β-amino and β-hydroxy phosphonic acids as well, both of which are endowed with interesting biological properties. According to the reported literatures, the synthesis of β-ketophosphonates mainly include:(1) the reaction of α-haloketones with trialkylphosphites(Michaelis-Arbuzov Rearrangement);(2) the acylation of alkylphosphonates with carboxylic acid derivatives by employing stoichiometric amounts of organometallic reagents;(3) the hydration of alkynylphosphonates;(4) the direct oxyphosphorylation of alkenes with dioxygen and H-phosphonates. However, almost all of these methods suffer from limitations such as poor product yields, low atom economy, inaccessible materials, tedious procedures, requiring excess amounts of organometallic reagents, long reaction time, or other relatively harsh reaction conditions. Therefore, the development of convenient, efficient, and especially benign methods to access β-ketophosphonates is still highly desirable in synthetic chemistry.At first, we develop a highly efficient and environmentally friendly silver-catalyzed hydration of alkynylphosphonates to β-ketophosphonates at 100 °C in water. Compared with mercury-catalyzed, palladium-catalyzed or gold-catalyzed, the described catalytic system will be more useful in synthetic programs. The disadvantage of the method is that one must synthesize the starting materials, alkynylphosphonates in advance. And after a persistent search,we disclose an unprecedented synthetic approach by which a series of β-ketophosphonates are readily prepared by direct oxyphosphorylation of alkynes with H-phosphonates and oxygen in the air in the presence of silver/copper cocatalysts and K2S2O8 within 3 hours at room temperature. The whole methodology has simple process, easy operation, high atom economy, cheap and accessible raw materials and catalysts. Finally, we comprehensively expound the mechanism of the oxyphosphorylation by a variety of means such as nitrogen atomosphere, radical scavenger and 31 P NMR stacks.The main contents of this paper are as follows:1. The chemcial properties, biological activities and synthesis methods for the synthesis of β-ketophosphonates were introduced and summarized.2. A highly efficient and environmentally friendly silver-catalyzed hydration of alkynylphosphonates to β-ketophosphonates was developed. Ag NO3 can take the place of Hg, Pd or Au as catalyst of the hydration of alkynylphosphonates to β-ketophosphonates. Then 34 compounds were synthesized, and all structures were confirmed by 1H NMR、13C NMR、31P NMR、HR MS.3. The reaction conditions were optimized from the respects such as catalyst, cocatalyst, oxidant, the ratios of reactants, solvent and time with the template reaction of phenylacetylene and diethyl phosphate. Then 35 compounds were synthesized, and all structures were confirmed by 1H NMR、13C NMR、31P NMR、HR MS.4. Finally, we studied the mechanism of this reaction with designed experiments. The results suggested that the oxyphosphorylation of alkynes with H-phosphonates and oxygen in the air undergone through a free radical mechanism not via a hydration of alkynylphosphates.