Acetonitrile-dependent Oxyphosphorylation: Synthesis Of β-ketophosphonates From Alkenyl Acids Or Alkenes

β-Ketophosphonate are versatile intermediates for various synthetically useful transformations,especially for the construction of alkenes through the well known Horner-Wadsworth-Emmons（HWE）reaction.β-Ketophosphonates also exhibit interesting bioactivities and prominent metal-complexing abilities.They have been successfully applied as extractants for transition elements,lanthanides,actinoid and alkali metals etc.Great efforts have been made during the past several decades to synthesize β-ketophosphonate scaffolds.Earlier synthetic methods mainly include Arbuzov reaction,and hydration of alkynylphosphonates catalyzed by palladium（II）and gold（I）catalysts.However,nearly all those earlier developed methods suffer from inaccessible materials,and moreover,for some reactions,expensive catalysts,or harsh basic or acidic reaction conditions are required.Over the past few years,the other synthetic methods concerning direct oxyphosphorylation of alkynes and alkenes with H-phosphonates were subsequently reported,respectively.Then,the use of both α,β-alkynyl carboxylic acids and α,β-alkenyl carboxylic acids,synthetically as terminal alkyne and alkene equivalents,began to be reported in the literature,It is worth mentioning here that,direct use of α,β-alkynyl carboxylic acids and α,β-alkenyl carboxylic acids has some advantages,such as no unpleasant smell,easy handling and storage due to they are solids.However,nearly all those developed methods suffer from expensive catalysts,or basic reaction conditions are required.Thus,more benign,efficient and atom-economic synthetic strategies have been pursued aggressively over the past few years.An efficient one-pot synthesis of β-ketophosphonates has been developed,via the reaction of α,β-alkenyl carboxylic acids or alkenes with H-phosphonates and air oxygen,catalyzed by Cu SO4·5H2O in CH3 CN.CH3CN plays a decisive role,probably by forming an active oxygen complex [（Me CN）n CuII-O-O·].It is well known that acetonitrile is an excellent ligand for copper（II）ion,it is pity that oxidation reactions participated by copper（II）-acetonitrile complex have been reported rarely.In a sharp contrast to other methods,the most prominent advantage of our reaction is using common and inexpensive Cu SO4·5H2O,instead of using much more expensive catalyst.The advantages also include a base-free condition and a wide reaction scope.The scope of the reaction encompasses both alkenyl carboxylic acids and alkenes,being suitable for transformation of not only alkenyl carboxylic acids but also alkenes into the corresponding β-ketophosphonates.In mechanism research,through radical scavenger,nitrogen atmosphere,isotope labeling experiment means,etc,the mechanism of the reaction was in-depth studied.The main contents of this paper are as follows:1.The chemical properties,application and synthesis methods of β-ketophosphonates were introduced and summarized.2.The reaction conditions were optimized from the respects such as solvent,catalyst,temperature and amount of H-phosphonate with the template reactions of cinnamic acid with diethyl H-phosphonate.Under the optimized conditions,the scope and regularity of this reaction were investigated.By employing a large variety of α,β-alkenyl carboxylic acids or alkenes with H-phosphonates,28 compounds were synthesized with structural elucidation by 1H NMR,¹³ C NMR,³¹ P NMR and HRMS.3.The mechanism of the reaction was explored by variety of means,such as radical scavenger,nitrogen atmosphere,isotope labeling and so on,and the mechanism of the reaction was in-depth studied.4.The reaction conditions were optimized from the respects such as solvent,catalyst,temperature and amount of H-phosphonate with the template reactions of styrene with diethyl H-phosphonate.And under the optimized conditions,the scope and regularity of this reaction were investigated.By employing a large variety of alkenes including internal alkenes with H-phosphonates,20 compounds were synthesized with structural elucidation by 1H NMR,¹³ C NMR,³¹ P NMR and HRMS.