Multifunctional Nitrogen Phosphine Ligands Control Palladium Catalyzed New Organic Reactions

Design of efficient and multi-funuctional phosphine ligands and development of recyclable Palladium/Ligand catalytic systems for new C-C/C-N bond forming reactions is of highly interests.In this context,a seris of novel N,P-ligands were successfully obtained.With the library of hetero-phosphine ligands,a highly efficient allylation of activated acetamides under environmentally benign process was developed,leading to novel mono-substituted and double-substituted products in excellent yields and chemo-selectivity.Based on the high efficiency of the first generation of N,P-ligand(L1)on chemo-selective allylation,we modified the ligand with PEG-2000 substituents for inhencement of water solubility.With the hydropholic analogue(L10)of L1,the Pd-catalyzed double allylation of acetamides with allylic acetate was able to proceed in aqueous media.Further,we extended the application of recyclable Pd/L10 catalytic system,the challaging intermolecular carbonylative coupling reaction could be accomplished in water leading to a,p-unsaturated 1,4-dicarbonyl esters in good yields.A new strategy on construction of highly-functionalized 1,2,3,4-hydroqulionone-2-one was developed under the Pd/L1 catalytic system via a sequential double-enolate benzylation/intramolecular amidation approach.A broad scope of substrate was tolerated in the tandem reaction.The mechanism study on these reactions and the investigation of catalytic species was analyzed by HR-MS,NMR,FT-IR and X-Ray diffraction.The novelty of this article are included as follows:(1)modulation of s-triazinal core is of vital important in this work.A variety of novel s-triazine based N,P ligands was synthesized via sequential nucleophilic substitution of each chlorides.This method on chemical modulation of s-triazine core afforded a unique schiff-base-based phosphine ligand(L1)with highly catalytic performance on controllable allylation process in PEG-400.In the presence of catalytic amount of Pd organometallic species and L1,cyano-containing amides reacted with simple allylic acetates smoothly under mild conditions.Furthermore,the Pd(OAc)2/L1/PEG-400 system could be recycled for 5 times with thoughout high yields of mono-allylated acetamides.On the basis of initial expermiments,the double allylation could also be achieved by changing the temperature and the bases.Under the the same catalytic systems,diverse double-allylated cyanoacetamides could be obtained in the presence of excess amount of KOtBu.The chemical deravitions of mono-and double-allylated cyano-containing acetamides could make the development of this catalytic system of highly importance.Under the Pd/L1 catalytic system,30 examples of both mono-and double-allylated cyano-containing acetamides were obtained with satisfactory yields.Through HR-MS analysis,the pre-calalyst was a tetra-coordinated Pd/L species with 1 equiv of L1 and 2 equiv of MeCN.Through 1HNMR and 31PNMR analysis,the ligand exchanges with allylic acetate was deteceted,which demonstrated the novel L1 could activated the allylic acetate.With the assistance of s-triazine core and extra bases,the attack of enolate on the Pd intermediate proceeded smoothly,giving the product by reductive elimination process on the palladium center.Hence,the s-triazine based Schiff-based N,P ligands prove to be a multi-functional ligands and showed potential industrial applications.(2)In this work,modified hydropholic N,P ligand analogue L10 was obtained via multiple-steps on modulation of s-triazine core.Based on the experimentation of the relationship between the yields of desired chalcones and the Schiff-base/Phosphine ligand structures,an intermolecular Heck-typed carbonylative reaction of aromatic triflates with phenyl-substituted alkenes or aryclated esters in pure water under Pd(OAc)2/L10 catalytic systems was developed.Various α,β-unsaturated 1,4-dicarbonyl esters were given in the presence of the optimized conditions.Chemical derivation experiments were conducted by mixturing the prepared chalcones with weinreb amides under 1 equivalent amount of Na2CO3,diverse[3+2]cycloaddition products could be obtained in satisfactory yields.Therefore,this work was featured in novel,recyclable and hydropholic property of the as-prepared ligand(L10)as well as the good performance on carbonylative Heck coupling reaction in water for the first time.(3)Under the developed Pd/s-triazine based phosphine ligand(GPS-Phos)catalytic system,the repeated enolated benzylation/intramolecular amidation process was accomplished in one-pot smoothly,affording diverse hydroqulionone-2-ones in moderate to good yields.This strategy was featured in terms of achievement of structural complexcity starting from relatively simple reagent,giving three bonds,one ring and quarternary stereo-center.Also with the developed catalytic system,four component double-benzylation/intramolecular amidation/Suzuki-Miyaura coupling reaction could be proceeded in PEG-400.The broad scope of substrates leads the methodology necessary.Also,the large-scale synthesis of highly-functionalized 1,2,3,4-hydroqulionone-2-one under the catalytic system makes the reaction applicable in industrial process.HR-MS and H-NMR analysis indicated that the chelated PdL1C12 was activated species for the C-N coupling reactions.(4)Syntheis functionalized carbonyl-containing compounds enabled by multi-functional ligand via a Pd-catalyzed conjugated-elimination process was disclosed in this section.By using a BINOL-skeleton derived N,P-Phos,various activated acetamides could reacted with MBH adducts in satisfactory yields.Under the Pd/N,P-Phos/A1 catalytic systems,this allylation reaction exhibit highly regio-selectivity,affording entirely γ-substituted cyano-containing amides with multiple hurdles.35 examples of novel carbonyl-containing amides were obtained under this catalytic systems,which prove it to be a multi-functional ligand.