Pd-catalyzed Aminocarbonylation/Alkoxycarbonylation Reaction Free Of Additives

Carbonylation is a CO-involved reaction process for the efficient syntheses of high value-added carbonyl compounds using easily available halides,alkenes,or alkynes,etc.as well as nucleophiles?amines,alcohols,water,etc.?as substrates,which is generally catalyzed by ligand-modified transition metal complexes.Ligands and transition metal catalysts play indispensable roles in carbonylation reaction,wherein phosphine-modified Pd-catalysts are widely used and studied because of their high catalytic activity and wide compatibility for substrate functional groups.In addition,auxiliary agents?such as Lewis/Br?nsted acid/base,etc.?are commonly used in carbonylation reaction.For example,bases?as acid scavengers?are usually required to ensure the smooth progress of the aminocarbonylation reactions of aryl halide.In the hydroaminocarbonylation of alkynes,acidic additives?such as Lewis/Br?nsted acids?are necessary to ensure the formation of Pd-H active species.However,the use of auxiliary agents not only increases the complexity of the reaction system and reduces the generality of the substrate scope,but also destroys the catalytic active species and induces some side-reactions.Based on the disadvantages caused by the involvement of auxiliary additives in the current Pd-catalyzed carbonylation reaction,in this thesis,the additive-free aminocarbonylation and alkoxycarbonylation over phosphine-modified Pd-catalysts were investigated,wherein the selection of reaction substrates and the design of functional ligands were emphasized.The research results obtained are summarized as follows:?1?Pd-catalyzed aminocarbonylation of aryl halides/alkynes using NH₄HCO₃ as ammonia surrogate free of auxiliary additiveAminocarbonylation reaction is an efficient and important method for the one-step synthesis of amide compounds.Compared with N-substituted amide compounds,primary amide compounds are more widely used in lubricants,medicines,and agrochemicals because of their diversified derivatives.However,examples on the efficient synthesis of primary amides by aminocarbonylation were rarely reported.In this part,the cheap and easily available NH₄HCO₃ was used for the first time for the synthesis of primary amides through aminocarbonylation reaction.It was found that in aminocarbonylation of aryl halides,CO and NH₄HCO₃,without the addition of auxiliary base,the primary amides were obtained in high yields over by the Pd-catalyst modified by the rigid biphosphine of Xantphos.In this reaction,NH₄HCO₃dually served as ammonia surrogate and acid-scavenger.The in situ decomposition of NH₄HCO₃ resulted in the release of NH₃ a nucleophile for the efficient generation of the target primary amides.Meanwhile,as an acid scavenger,NH₄HCO₃can effectively neutralize the formed HX acid?to generate thermodynamically stable CO₂?and then drove up the reaction progress smoothly.On the other hand,the use of weak basic NH₄HCO₃ also could inhibit the dehydration or polymerization of the product primary amide,which greatly facilitated the selectivity of the primary amide products.Comparatively,in the aminocarbonylation of alkynes,CO and NH₄HCO₃as a 100%atom-economic reaction,the target?,?-unsaturated primary amides were obtained in high yields over the Pd-catalyst modified by the biphosphine of Dppp with natural bite angle of 91^o without the addition of any auxiliary additive.In this reaction,NH₃ as the required nucleophile was released upon in situ decomposition of NH₄HCO₃.It was verified that the in situ released H₂CO₃?CO₂ and H₂O?could provide proton and then promote the generation of Pd-H active species,leading to the efficient aminocarbonylation in the absence of auxiliary additive.?2?Pd-catalyzed aminocarbonylation of alkynes with aliphatic amines free of auxiliary additive and its mechanism studyIn aminocarbonylation of alkynes,CO and amines,it is generally believed that the strong alkalinity of the involved aliphatic amines will quench the formed Pd-H active species,resulting in the failure of the aliphatic-amine-involved aminocarbonylation.Encouragingly,in this part,the aminocarbonylation of alkynes,CO and aliphatic amines free of auxiliary additive were successfully achieved.Accordingly,the new mechanism for such aminocarbonylation reaction was proposed wherein the unique carbamoylpalladium complex intermediate,instead of the widely accepted palladium-hydride?Pd-H?species,was belied to be the real catalytic active species,based on the related control experiments and characterization analyses.?3?Pd-catalyzed alkoxycarbonylation of electron-deficient olefins free of auxiliary additive with the present of a tri-functional ligandThe poor reactivity of the electron-deficient olefins?such as methyl acrylate and its derivatives?often results in the low efficiency in alkoxycarbonylation of olefins,CO and alcohols due to the low cloud density and weakened coordination ability of the involved carbon-carbon double-bond.Hence,a large amount of acid additives is necessarily added to promote and stabilize Pd-H active species to ensure this reaction.In this part,a tri-functional ligand L4 containing phosphino,phosphonium and SO₃^--group was synthesized by using the biphosphine of Xantphos as a parent molecule.It was found that L4-modified Pd-catalyst could cooperatively activate Me OH to be a proton-source,facilitating the generation of Pd-H active species.The later was responsible for the efficient alkoxycarbonylation of methyl acrylates and its derivatives free of any acid additive.The functionalized ligand of L4 was structurally features with the following points:?1?The introduced phosphino-moiety?-PPh₂?could coordinate to Pd-center to stabilize the Pd-catalyst;?2?The introduced positive-charged phosphonium-moiety with Lewis acidity could activate alcohol molecules through acid-base pair interactions to promote the generation of Pd-H active species.?3?The introduced SO₃^--group could capture and activate alcohol molecules through hydrogen-bond interaction.In addition,the oxygen-atom of SO₃^-with weak coordination ability could also gave rise to the stability of the Pd-catalyst.