P,N-/P,O-Hybrid Ligands:Synthesis And Applications In Pd-Catalyzed Alkoxycarbonylation/Hydroaminocarbonylation Of Alkynes

Pd-catalyzed carbonylation of unsaturated hydrocarbons is a homogeneous catalytic reaction process for the atom-efficient synthesis of high value-added carbonyl compounds（carboxylic acids,carboxylate esters,amides,etc.）.Especially as for the carbonylation of alkynes performed under different catalytic systems,the mono-carbonylation can be directed to synthesizeα,β-unsaturated carbonyl compounds,or the double-carbonylation to afford succinic acid derivatives.It is well known that ligands play an indispensable role in the Pd-catalyzed carbonylation of alkynes,and their design and synthesis are the core content of the study of highly selective directional carbonylation.The electronic and steric effects of ligands can effectively regulate the catalytic performances（activity,selectivity and stability）of Pd catalysts.Among them,phosphorous-containing hybrid ligands,such as P,N-and P,O-hybrid ligands,exhibit unique regulatory effects on Pd catalysts due to their unique hemilability.Herein,a series of P,N-and P,O-hybrid ligands were designed and synthesized for Pd-catalyzed carbonylation of alkynes,including alkoxycarbonylation of alkynes,double-hydroaminocarbonylation of alkynes,and double-alkoxycarbonylation of alkynes with Pd relay catalysis modified by double ligands cooperation.The main results are summarized as follows:（1）Pd-catalyzed alkoxycarbonylation of alkynes for synthesis of branchedα,β-unsaturated carboxylate esters with involvement of multifunctional P,N-hybrid ligandsIn this part,P,N-hybrid ligands L1-L5 containing the backbones of oxalamido-,isophthalamido-and pyridine-2,6-dicarboxamido-moiety respectively were synthesized,and the catalytic performances of L1-L5 modified Pd catalysts on the alkoxycarbonylation of alkynes were investigated.The results showed that L5-modified Pd（Me CN）₂Cl₂ catalytic system containing the m-phenylxylamide skeleton,-PPh₂ fragment and-F substituents exhibited high catalytic activity and regioselectivity in the alkoxycarbonylation of alkynes.Characterization by X-ray single crystal diffraction and the in situ FT-IR techniques confirmed that L5 is a multifunctional ligand.On the one hand,in Pd-L5 complex formed by L5 and Pd（Me CN）₂Cl₂,the hydrogen bond is developed between the N-H bond in the amide group and Cl^-,which ensures the stability of the complex and is conducive to the dissociation of Cl^-,thus improving the active coordination of the catalyst.Secondly,the intramolecular hydrogen bonding of Pd-L5 is beneficial to enhance the stability of the catalyst.On the other hand,the potential hydrogen bonding of amide groups in L5 to the substrate alcohol can effectively activate the alcohol,thereby promoting the formation of Pd^Ⅱ-H species(v 1956 cm^-1),which plays a synergistic catalytic role.The constructed L5-Pd（Me CN）₂Cl₂ catalytic system showed good substrate universality.（2）Pd-catalyzed bis-hydroaminocarbonylation of terminal alkynes for synthesis of N-aryl substituted succinimides with involvement of ionic P,O-hybrid ligandIn this part,the novel ionic P,O-hybrid ligands L8-L11 were synthesized via re-constructing the bidentate phosphine ligands Xantphos or（R）-BINAP.The catalytic performances of these ligands（L8-L11）modified Pd on the bis-hydroaminocarbonylation of terminal alkyne were investigated.The results showed that the L8-modified Pd（Me CN）₂Cl₂ system exhibited high activity,excellent selectivity and good stability.The single crystal structure of L8 proved that it could be used as a tetra-pedate P,O-hybrid ligand.XPS analysis also demonstrated the presence of P,O-chelation in the complex Pd-L8.The results of in situ FT-IR characterization,kinetic monitoring and control experiments further revealed that the L8-Pd（Me CN）₂Cl₂system catalyzed bis-hydroaminocarbonylation of terminal alkyne followed the Pd^Ⅱ-H reactive species reaction mechanism.The steric effect and the hemilability of the P,O-chelation effect in L8 facilitate the formation and stabilization of the Pd^Ⅱ-H species(v 1942 cm^-1),as well as the regioselectivity of the branched productsα,β-unsaturated amides.In addition,the L8-modified Pd（Me CN）₂Cl₂ catalyst had good substrate universality and stability,and could be cumulatively recycled for 5 times（120 h）without obvious inactivation.（3）Pd-relay-catalysis for bis-alkoxycarbonylation of terminal alkynes to succinic acid diestersIn this part,the relay-catalysis over Pd-catalyst with involvement of the two kinds of ligands of L7 and L9 was achieved successfully in bis-alkoxycarbonylation of terminal alkynes for synthesis of succinic acid diesters.As a P,O-hybrid ligand,L7 via forming a stable cis-complex Pd-L7 with Pd（Me CN）₂Cl₂ was responsible for first-step alkoxycarbonylation of terminal alkynes to selectively form the branchedα,β-unsaturated carboxylate esters.Then the ionic biphosphine of L9 was responsible for the second-step alkoxycarbonylation of branchedα,β-unsaturated carboxylate esters to generate the target products（2-alkylp-or aryl-substituted succinate）.The in situ high-pressure FT-IR characterization,reaction kinetics monitoring and control experiments proved that L7 and L9 could independently coordinate with Pd-center to form two distinct catalytic systems.Therein,the L7-modified Pd-catalyst showed high activity toward the first-step alkoxycarbonylation along with excellent regioselectivity for the branchedα,β-unsaturated carboxylate esters.And the L9-modified Pd-catalyst had good activity for the second-step alkoxycarbonylation ofα,β-unsaturated carboxylate esters.