Olefin Insertion Versus Cross-Coupling in trans-[Pd(Ar)X(AsPh3)2] Complexes (X = I, F, CF3) Treated with a Phosphine-EWOlefin Ligand to Induce Ar–X Coupling

Producción CientíficaAddition of the coupling promoter PEWO ligand 1-(Ph2P),2-(CH═CH–C(O)Ph)C6F4 (PhPEWO-F) to precursors with the displaceable AsPh3 ligand trans-[PdXAr(AsPh3)2] (X = I, F, CF3) fails to induce the pursued Ar–F or Ar–CF3 coupling and results in formation of products of olefin insertion into the Pd–Ar bond for X = I, CF3, and in Ar–Ar coupling for X = F. In the course of the processes, trans-[PdXAr(PhPEWO-F)(AsPh3)] intermediates are observed for X = I, F, CF3, with P-coordinated PhPEWO-F monodentate ligands and a dangling olefin group. For X = I, CF3, subsequent insertion of the double bond into the Pd–Ar bond and O-coordination gives rise to complexes with a P,C,O-pincer system. The observed insertion rates suggest that the limiting step toward insertion is the trans to cis isomerization, while insertion itself is very fast. This is supported by the fast insertion observed when PhPEWO-F is added to cis-[Pd(CF3)Ar(3-F-py)2]. The insertion mechanism in PhPEWO-F resembles the initial phase of the dearomative rearrangement mechanism reported for PdArBrL (L = dialkyl biaryl phosphine).Ministerio de Economía, Industria y Competitividad (Projects CTQ2014-52796-P, CTQ2016-80913-P, and CTQ2014-52974-REDC)Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA256U13

E–Z Isomerization of Phosphine-Olefin (PEWO-F4) Ligands Revealed upon PdCl2 Capture: Facts and Mechanism

Producción CientíficaThe PEWO phosphines R2P(o-C6H4CH═CHC(O)Ph), R2P(o-C6H2F2CH═CHC(O)Ph), and R2P(o-C6F4CH═CHC(O)Ph) and their P-monodentate complexes trans-[PdCl2(P-monodentate)2] show, in solution and (when available) in the X-ray diffraction structures, an E configuration of the double bond. In contrast, the structures of [PdCl2(P-chelate)] display E and Z configurations. The E/Z isomerization of the latter requires first decoordination of the double bond, which then allows for easy rotation about the electron-deficient double bond. Thus, the E/Z equilibria exist for the free and the P-monodentate complexes as well but are not observed because they are extremely displaced toward the E isomer. Their capture in the form of [PdCl2(P-chelate)], with equilibrium constants on the order Keq ≈ 1–3, allows the two configurations to be observed and isolated. Evaluation of their ability to couple Pf–Pf from cis-[PdPf2(THF)2] (Pf = C6F5) affords values of their ΔG⧧(Pf–Pf)Pd parameters confirming that higher substitution of H by F produces lower coupling barriers and a double bond that is more electron deficient when it is free and more electron withdrawing when it is coordinated.Junta de Castilla y León (projects VA051P17 and VA062G18)Ministerio de Economía, Industria y Competitividad (projects CTQ2016-80913-P and CTQ2017-89217-P

Experimental Study of the Mechanism of the Pd-catalyzed Aryl-alkyl Negishi Coupling using Hybrid Phosphine- Electron Withdrawing Olefin Ligands

Producción CientíficaA detailed study of the Negishi cross-coupling reaction of ArI (Ar = 2-C6H4CO2Et) and ZnEt2 with palladium catalysts containing conventional phosphines versus one using a chelating hybrid phosphine–electron-withdrawing olefin (P-EWO) ligand reveals that for conventional phosphines (e.g., PPh3) β-H elimination from intermediate [PdArEt(PPh3)2] is competitive with Ar–Et reductive elimination and is responsible for part of the undesired reduction product ArH. In contrast, with the EWO phosphine, the β-H elimination from intermediate [PdArEt(P-EWO)] is slow compared to the fast Ar–Et reductive elimination, and the undesired reduction product ArH observed proceeds in this case of hydrolysis of ZnArEt, formed in transmetalations where Ar is transferred from Pd to Zn. The rate of these transmetalations is comparable to the rate of reductive eliminations. Consequently, undesired transmetalations affording [PdEt2(P-EWO)] and ZnArEt are more effective at early stages of the reactions and less effective when the ethylating agent becomes poorer in ZnEt2 and richer in ZnEtX (X = I), as the reaction proceeds. Careful analysis of the experiments reveals the detailed changing evolution of the reaction, not only providing the main features of the catalytic cycle but also deducing how the reagents in the system change with time and what the effects on the products of these changes are.Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. GR169 and VA256U13)Ministerio de Economía, Industria y Competitividad (CTQ2013-48406-P

Organometallic nucleophiles and Pd: What Makes ZnMe2 Different? Is Au like Zn?

Producción CientíficaThe cis/trans isomerization of [PdMeAr(PR3)2] complexes (Ar = C6F5, C6F3Cl2) can take place spontaneously (via dissociation and topomerization, studied experimentally) or catalyzed by ZnMe2. The later mechanism, studied by DFT methods, involves methyl exchange between Pd and Zn. The study of this catalyzed isomerization shows that, in contrast with the typical acidic behavior of Zn in ZnMeCl, Zn in ZnMe2 (or, more exactly, the ZnMe bond) behaves as a strong basic center, able to attack the relatively high in energy acceptor orbital at Pd in fairly electron rich Pd complexes such as [PdArMeL2] or [PdMe2L2]. This makes the two reagents very different in Negishi couplings. The catalyzed isomerization occurs via transmetalation, thus both processes are connected. A comparison of the Pd/Zn intermediates and transition states with those found previously for Pd/Au transmetalations reveals very similar structures with intermetallic distances in the order of or noticeably shorter than the sum of the vdW radii, regardless of the nature of the metal (metallophilic Au or non metallophillic Zn). These short distances are associated to the involvement of the metals in 3c2e electron deficient bonds during R group transmetalation. In this respect there is a remarkable similarity with the structurally known behavior of main-group electron-deficient compound, which supports a unified view of the transmetalation processes.Ministerio de Economía, Industria y Competitividad (CTQ2013-48406-P)Ministerio de Economía, Industria y Competitividad (CTQ2012-37734)Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA256U13)Centro de Supercomputación de Galicia (CESGA, ICTS240-2013 and ICTS257-2014

Ranking Ligands by Their Ability to Ease (C6F5)2NiIIL → Ni0L + (C6F5)2 Coupling versus Hydrolysis: Outstanding Activity of PEWO Ligands

Producción CientíficaThe NiII literature complex cis-[Ni(C6F5)2(THF)2] is a synthon of cis-Ni(C6F5)2 that allows us to establish a protocol to measure and compare the ligand effect on the NiII → Ni0 reductive elimination step (coupling), often critical in catalytic processes. Several ligands of different types were submitted to this Ni-meter comparison: bipyridines, chelating diphosphines, monodentate phosphines, PR2(biaryl) phosphines, and PEWO ligands (phosphines with one potentially chelate electron-withdrawing olefin). Extremely different C6F5–C6F5 coupling rates, ranging from totally inactive (producing stable complexes at room temperature) to those inducing almost instantaneous coupling at 25 °C, were found for the different ligands tested. The PR2(biaryl) ligands, very efficient for coupling in Pd, are slow and inefficient in Ni, and the reason for this difference is examined. In contrast, PEWO type ligands are amazingly efficient and provide the lowest coupling barriers ever observed for NiII complexes; they yield up to 96% C6F5–C6F5 coupling in 5 min at 25 °C (the rest is C6F5H) and 100% coupling with no hydrolysis in 8 h at −22 to −53 °C.Ministerio de Economía, Industria y Competitividad (Projects CTQ2017-89217-P and CTQ2016-80913-P)Junta de Castilla y León (projects VA051P17 and VA062G18)Ministerio de Economía, Industria y Competitividad FPI scholarship (BES-2017-080726

Promoting difficult coupling processes: synthesis of phosphine-olefin hybrid ligands, reactivity and reductive elimination studies

The work developed during this doctoral thesis involves the design, synthesis, characterization and evaluation of the catalytic activity of a family of hybrid phosphine-olefin (PEWO) ligands that are able to promote challenging coupling processes. The memory is organized in five main blocks: Introduction, Results and Discussion, Experimental Section, Resumen en español (Spanish Summary) and Annex. First of all, the introduction presents concepts related to the four main topics treated: Ligand design, Reductive elimination promoted by ligands, Negishi reaction mechanism and Reductive elimination in Ni. The results obtained have led so far to the publication of several articles, although there are others that are in the process of being published. In the Results and Discussion block brief comments about the former, as well as full description of the later (drafts) are presented. The experimental characterization of the compounds and detailed explanation of some experiments is gathered in the Experimental Section. In addition, according to the Spanish regulation of Doctoral Thesis, a brief summary of the thesis written in Spanish is included. Finally, the Articles published (with the corresponding Supporting Information) in the original format of the paper are reproduced.Departamento de Química Física y Química InorgánicaDoctorado en Química: Química de Síntesis, Catálisis y Materiales Avanzado

Understanding the Use of Phosphine-(EWO) Ligands in Negishi Cross-Coupling: Experimental and Density Functional Theory Mechanistic Study

Producción CientíficaThe easily prepared hemilabile ligand 1-(PPh2),2-(trans-CH═CHCOPh)–C6F4 (PhPEWO-F) and other PEWO ligands are well-known promoters of C–C reductive eliminations and very effective in Negishi couplings. As an example, the efficient Negishi coupling of (C6F5)–I and Zn(C6F5)2 is reported. The thorough experimental study of the steps involved in the catalytic cycle uncovers the potential weakness of this ligand that could frustrate at some points the desired cycle and provide some simple precautions to keep the catalytic cycle working efficiently. Density functional theory (DFT) calculations complete the experimental study and provide insight into nonobservable transition states and intermediates, comparing the potential conflict between reductive elimination and olefin insertion. Our results showcase the importance the transmetalation step, facilitated by the strong trans effect of the electron-withdrawing ligand, and the choice of organozinc nucleophiles, critical to ensure fast group exchange and a positive outcome of the catalytic reactions.Ministerio de Economía, Industria y Competitividad (project CTQ2017-89217-P)Junta de Castilla y León (project VA062G18