Mono/Multi-Dentate Phosphines:Synthesis And Applications In Pd-Catalyzed(Bis-)Carbonylation Of Alkynes

Carbonylations of alkynes are processes for the conversion of alkynes,CO and nucleophiles?alcohols,amines,water,etc.?into saturated or unsaturated carboxylic acid and their derivatives,which are typically catalyzed by Pd-catalysts modified by phosphine ligands.It has been well known that the steric and electron effects of phosphine ligands greatly influence the activity,selectivity and stability of catalysts,among which the multi-dentate phosphines exhibit excellent performance in stabilizing metal centers due to their flexible multi-chelation mode.Moreover,the?-feedback interaction between P and Pd can facilitates the migration of CO and its insertion into Pd-R bond,giving rise to the formation of acyl palladium intermediates Pd-?CO?R.Hence,the phosphines with intensive?-accepting ability can improve the catalytic performance of Pd-catalysts.Besides of phosphine ligands,auxiliary additives?such as Br?nsted acid,Lewis acid and H₂O?also play important roles in spurring the performance of Pd-catalysts.The addition of auxiliary additives can facilitate the generation and stabilization of Pd-H active species,which are responsible for the efficient carbonylations.Based on the significance of phosphines with multi-dentate and intensive?-accepting ability as well as the importance of additives in the Pd-catalyzed carbonylations,the research work in this thesis are carried out from the following two aspects.?1?Synthesis and characterization of multi-dentate phosphine ligands and their applications for Pd-catalyzed alkoxycarbonylation of alkynes promoted by H₂O additiveA series of novel multi-dentate phosphines with good robustness against water and oxygen were synthesized and fully characterization?Scheme 1?,which were applied to Pd-catalyzed alkoxycarbonylation of alkynes promoted by H₂O additive.It was found that the developed ionic tri-dentate phosphine?L2'?enabled Pd-catalyzed alkoxycarbonylation of alkynes most efficiently while H₂O was used as additive instead of acid.As for L2',its unique steric configuration with two types of potential P-P chelation modes?P…P distance of 4.31?and 4.36?respectively?to Pd-centre rendered the corresponding Pd-catalyst high activity and good stability for alkoxycarbonylation of alkynes.Compared with the neutral phosphine?L2?,the ionic phosphine L2'exhibited intensive?-accepting ability due to the electron-withdrawing effect from positive-charged imidazolium ring on the neighbored P-atom.As a result,L2'modified Pd-catalysts exhibited higher activity than the structurally similar ligand?L2?under optimal reaction conditions.The in situ FT-IR analysis also verified that the formation and stability of Pd–H active species were greatly facilitated with the presence of L2'as well as H₂O additive.In addition,as an ionic phosphine,L2'based PdCl₂?MeCN?₂ system immobilized in RTIL of[Bmim]NTf₂ could be recycled for 7runs without obvious activity loss or metal leaching.?2?Bi-functional ligand based Pd-catalyst for the carbonylations of alkynes?bis-alkoxycarbonylation,aminocarbonylation and hydroxycarbonylation?Both phosphine ligands and acid additives can significantly promote the formation and stability of Pd-H active species in Pd-catalyzed carbonylations of alkynes.However,the physical mixture of excess Br?nsted acids and phosphines lead to the following problems:excess protons quench the Pd-H active species,accompanied by the release of H₂([Pd^II-H]⁺+H⁺?Pd^II+H₂-);phosphine ligands are prone to alkylation and lead to the self-inactivation.On the other hand,the metal salts introduced by Lewis acid additives(Al³⁺,Fe³⁺)complicate the catalytic system.In this part,two kinds of bi-functional ligands L4 and L6 were successfully constructed,which bonded“phosphine”and“organic acid”in a molecular.The synergistic effects of“phosphine-SO₃H”bi-functional ligand?L4?based Pd-catalyst on the bis-alkoxycarbonylation/aminocarbonylation of alkynes and the“phosphine-phosphonium”bi-functional ligand?L6?based Pd-catalyst on the hydrocarboxylation of alkynes were investigated.?2.1?“Phosphine-SO₃H”bi-functional ligand based Pd-catalyst for bis-alkoxycarbonylation of alkynesThe bi-functional ligand?L4?containing diphopshino-fragment and sulfonic acid group?-SO₃H?succesfully enabled Pd-catalyst to efficiently catalyze the tandem bis-alkoxycarbonylation of terminal alkynes to produce aryl-/alkyl-substituted succinate?Scheme 2?.It was found that the incorporated-SO₃H in L4 indispensably assisted Pd-catalyst to accomplish this tandem reaction via intramolecular synergic effect.The bi-functional ligand based Pd-catalyst was not a result of the physical mixture of Xantphos and MeSO₃H.The in situ FT-IR analysis verified that the formation and stability of Pd-H active species was facilitated with the presence of L4.The formation of stabilized diacylpalladium intermediate?F?was the critical driving force for the second-step methoxycarbonylation.The DFT calculation was carried out to optimize the geometric structure of F,which indicated that the developed intramolecular O???H hydrogen bonds were the important structural feature to stabilize F.In addition,L4-based Pd-catalyst could be recycled successfully in the ionic liquid of[Bmim]NTf₂ without the obvious activity loss and the detectable metal leaching.?2.2?“Phosphine-SO₃H”bi-functional ligand based Pd-catalystfor aminocarbonylation of alkynes with amidesThe bi-functional ligand?L4?based Pd-catalyst was successfully applied in the aminocarbonylation of alkynes with amides to construct?,?-unsaturated imide?Scheme 2?.The incorporated phosphine group and sulfonic acid group were compatible with each other to achieve the intramolecular synergy.The catalytic system showed higher activity for aminocarbonylation of alkynes with amides than the physical mixture of two functional groups.The in situ FT-IR analysis verified that the formation and stability of Pd-H active species were facilitated with the presence of bi-functional ligand L4.Under the optimized conditions,the aminocarbonylation products of various alkynes and amides were obtained with the yields in the range of 46%-87%.Advantageously,as an ionic ligand,L4-based Pd-catalyst could be recycled for 6 runs in the ionic liquid of[Bmim]NTf₂ without the obvious activity loss and the detectable metal leaching.?2.3?“Phosphine-phosphonium”bi-functional ligand based Pd-catalyst for hydroxycarbonylation of alkynesThe bi-functional ligand?L6?based Pd-catalyst was successfully applied in the hydroxycarbonylation of terminal alkynes?Scheme 3?.The results showed that:the-PPh₂ group which coordinated with Pd could protect metal centre from inactivation;[P?V?⁺]?Lewis acid?could activate H₂O to promote the generation of Pd-H active species,and activate the carbonyl intermediates to promote the process of carbonylation.These two different groups were effectively separated by the rigid Xanthene ring to avoid the quenching reaction of“acid-base”pair.L6-based Pd-catalyst exhibited higher activity than the physical mixture of two functional groups.Moreover,O-atom in sulfonate with hemilabile effect could assistantly stabilize Pd²⁺centre;this kind of hydro-oil amphiphilicity ligand rendered both H₂O molecules and alkynes better accessibility to P-Pd²⁺catalytic sites,which also gave rise to the reaction rate.Under the optimized conditions,the hydrocarboxylation products of various alkynes were obtained with yields in the range of 68%-91%in the catalytic system.In addition,as an ionic ligand,L6-based Pd-catalyst could be recycled for 6 runs in the ionic liquid[Bmim]NTf₂ without the obvious activity loss and the detectable metal leaching.