Juan A. Casares

Bimetallic Catalysis using Transition and Group 11 Metals: An Emerging Tool for CC Coupling and Other Reactions

Bimetallic catalysis refers to homogeneous processes in which either two transition metals (TM), or one TM and one Group 11 (G11) element (occasionally Hg also), cooperate in a synthetic process (often a C-C coupling) and their actions are connected by a transmetalation step. This is an emerging research area that differs from the isolated or tandem applications of the now classic processes (Stille, Negishi, Suzuki, Hiyama, Heck). Most of the reactions used so far combine Pd with a second metal, often Cu or Au, but syntheses involving very different TM couples (e.g., Cr/Ni in the catalyzed vinylation of aldehydes) have also been developed. Further development of the topic will soon demand a good knowledge of the mechanisms involved in bimetallic catalysis, but this knowledge is very limited for catalytic processes. However, there is much information available, dispersed in the literature, coming from basic research on exchange reactions occurring out of any catalytic cycle, in polynuclear complexes. These are essentially the same processes expected to operate in the heart of the catalytic process. This Review gathers together these two usually isolated topics in order to stimulate synergy between the bimetallic research coming from more basic organometallic studies and the more synthetic organic approaches to this chemistry.

Palladium round trip in the Negishi coupling of trans-[PdMeCl(PMePh2)2] with ZnMeCl: an experimental and DFT study of the transmetalation step.

Compared with the detailed mechanistic knowledge of the Stille reaction, little is known about the Negishi reaction. Recently, we experimentally uncovered the complicated behavior of the transmetalation of transACHTUNGTRENNUNG[PdRfClACHTUNGTRENNUNG(PPh3)2] (Rf= 3,5-dichloro-2,4,6-trifluorophenyl) with ZnMe2 or ZnMeCl, showing that each methylating reagent afforded stereoselectively a different isomer (trans or cis, respectively) of the coupling intermediate [PdRfMe ACHTUNGTRENNUNG(PPh3)2].[4] Moreover, the study revealed the occurrence of undesired transmetalations, such as those shown in Scheme 1, which could eventually produce homocoupling products; the corresponding undesired intermediates were detected and identified by NMR spectroscopy techniques. The formation of undesired intermediates in related reactions with aryl zinc derivatives was later observed by Lei et al. Herein, we report an experimental mechanistic study of the reaction of trans-[PdClMe ACHTUNGTRENNUNG(PMePh2)2] (1) with ZnMeCl, which affords the first experimental determination of thermodynamic parameters of a Negishi transmetalation. This is complemented with a theoretical DFT study, which provides a detailed view of the reaction pathway, consistent with the experimental parameters. The reactions of 1 with ZnMeCl were carried out (with one exception) in 1:20 ratio, simulating catalytic conditions with 5 % Pd, in THF at different temperatures. At room temperature, the only product observed was cis[PdMe2ACHTUNGTRENNUNG(PMePh2)2] (2), in equilibrium with the starting material 1. In these conditions, complex 2 undergoes slow decomposition (reductive elimination) to give ethane. When the reaction was monitored by P NMR spectroscopy at 223 K (Figure 1 a), the coupling rate to give ethane became negligible and the formation of trans-[PdMe2ACHTUNGTRENNUNG(PMePh2)2] (3), as well as cis-[PdMe2ACHTUNGTRENNUNG(PMePh2)2] (2), was observed. The trans isomer 3 seemed to be formed first and then disappeared. The same reaction, carried out at 203 K in 1:1 ratio to get a slower rate of transformation, confirmed that 3 is formed noticeably faster than 2 (Figure 1 b). Thus, the observation of the cis isomer at room temperature is deceptive for the stereoselectivity of the transmetalation. Snapshots of two moments of the transmetalation reaction at 203 K, as seen by P NMR spectroscopy, are shown in Figure 1 c. The behavior of 3 is typical of a kinetic product of noticeably lower stability than the thermodynamic product (2): eventually it disappears from observation as the reaction proceeds and gets closer to the equilibrium concentrations, where the concentration of 3 is very small. In effect, during the progress of the reaction at 223 K (Figure 1 a), the concentration of 2 increases continuously; in contrast, a small accumulation of 3 is produced initially and then its concentration decreases, so that in 300 min 3 has practically disappeared. After about 10 h at 223 K, the system has reached equilibrium between the starting complex 1 and the final thermodynamic product 2 ([1]=5.8 10 3 mol l , [2]=4.4 10 3 mol l , and Keq =2.0 10 ); the concentration of 3 is below the limit of NMR observation. [a] B. Fuentes, Dr. J. A. Casares, Prof. P. Espinet IU CINQUIMA/Qu mica Inorg nica Facultad de CienciasUniversidad de Valladolid 47071 Valladolid (Spain) Fax: (+34) 983423231/ ACHTUNGTRENNUNG(+34) 983186336 E-mail : casares@qi.uva.es espinet@qi.uva.es [b] M. Garc a-Melchor, Prof. A. Lled s, Prof. F. Maseras, Dr. G. Ujaque Qu mica F sica, Edifici C.n, Universitat Aut noma de Barcelona 08193 Bellaterra, Catalonia (Spain) Fax: (+34) 935812920 E-mail : gregori@klingon.uab.es [c] Prof. F. Maseras Institute of Chemical Research of Catalonia (ICIQ) Av. Pa sos Catalans, 16, 43007 Tarragona, Catalonia (Spain) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201001332. Scheme 1.

Cationic Intermediates in the Pd-Catalyzed Negishi Coupling. Kinetic and Density Functional Theory Study of Alternative Transmetalation Pathways in the Me–Me Coupling of ZnMe2 and trans-[PdMeCl(PMePh2)2]

The complexity of the transmetalation step in a Pd-catalyzed Negishi reaction has been investigated by combining experiment and theoretical calculations. The reaction between trans-[PdMeCl(PMePh(2))(2)] and ZnMe(2) in THF as solvent was analyzed. The results reveal some unexpected and relevant mechanistic aspects not observed for ZnMeCl as nucleophile. The operative reaction mechanism is not the same when the reaction is carried out in the presence or in the absence of an excess of phosphine in the medium. In the absence of added phosphine an ionic intermediate with THF as ligand ([PdMe(PMePh(2))(2)(THF)](+)) opens ionic transmetalation pathways. In contrast, an excess of phosphine retards the reaction because of the formation of a very stable cationic complex with three phosphines ([PdMe(PMePh(2))(3)](+)) that sequesters the catalyst. These ionic intermediates had never been observed or proposed in palladium Negishi systems and warn on the possible detrimental effect of an excess of good ligand (as PMePh(2)) for the process. In contrast, the ionic pathways via cationic complexes with one solvent (or a weak ligand) can be noticeably faster and provide a more rapid reaction than the concerted pathways via neutral intermediates. Theoretical calculations on the real molecules reproduce well the experimental rate trends observed for the different mechanistic pathways.

14-Electron T-shaped [PdRXL] complexes: evidence or illusion? Mechanistic consequences for the stille reaction and related processes.

A recent claimed spectroscopic observation (by (1)H NMR) of 14-electron T-shaped 3-coordinated palladium complexes turns out to be a misinterpretation. A thorough study of the species formed by [PdRX(AsPh(3))(2)] (R=Ph, C(6)Cl(2)F(3); X=Cl, I) in different solvents (S=CDCl(3), THF, DMF) suggests that: 1) there is no NMR-detectable amount of [PdRX(AsPh(3))], and 2) in the presence of free arsine (AsPh(3)/[PdRX(AsPh(3))(2)] 2:1) the concentration of [PdRX(AsPh(3))(S)] is negligible. This clearly settles matters in the controversy of dissociative or associative pathways for the transmetalation step involved in the Stille coupling in favor of the latter: under catalytic conditions the dominant pathway is the associative reaction of the stannane with the square-planar complex [PdRX(AsPh(3))(2)].

Strong Metallophilic Interactions in the Palladium Arylation by Gold Aryls

Its the second step that counts: arylation of Pd by Au takes place through transition states and intermediates featuring strong Au⋅⋅⋅Pd metallophilic interactions. However, the aryl transfer from [AuArL] to [PdArClL(2)] is thermodynamically disfavored and will not occur unless an irreversible Ar-Ar coupling from [PdAr(2)L(2)] follows.

Observation of a hidden intermediate in the Stille reaction. Study of the reversal of the transmetalation step.

A study of the reaction of cis-[PdRf2(AsPh3)2] (Rf = 3,5-C6Cl2F3) with ISnBu3 (that is the reversal of the natural Stille reaction of [PdRfI(AsPh3)2] with RfSnBu3) allows for the observation of cis-[PdRf2(AsPh3)(ISnBu3)], the expected intermediate from a cyclic transmetalation in the direct Stille reaction, thus providing experimental support to the operation of cyclic transmetalation pathways.

Efficient silylformylation of alkynes catalyzed by rhodium complexes with P,N donor ligands

Abstract The complexes [Rh(diene)(L-L′)](BF 4 ), and [RhCl(CO)(L-L′)] (diene=COD 1,5-cyclooctadiene; L-L′=P(bzN)Ph 2 , P(bzN) 2 Ph, P(bzN) 3 , PePy, or PePy 2 , bzN=2-(dimethylaminomethyl)phenyl, PePy n =P(CH 2 CH 2 Py) n Ph 3− n ; Py=2-pyridyl; n =1,2) are poor catalysts for the hydrosilylation of 1-hexyne, but excellent catalysts for the silylformylation of 1-hexyne in tetrahydrofurane at atmospheric pressure and room temperature.

Palladium-Mediated Organofluorine Chemistry

Abstract The importance of organofluorine compounds in pharmaceuticals and agrochemicals has encouraged the study of their synthesis since the middle of the twentieth century. In recent years, there has been a huge increase in the work devoted to improve the use of transition metals as catalysts for the formation of C F bonds and its activation, and also to the development of fluoroalkylation and fluoroarylation reactions. Palladium complexes, as undisputed protagonists in the catalyzed reactions for the formation of C C or C heteroatom bonds, have been employed for these reactions. However, the particular properties of fluorine and fluorinated hydrocarbons do not allow a straightforward translation of the palladium-catalyzed methodologies. This chapter provides an overview of the progress in palladium-catalyzed synthesis of organofluorinated compounds. It also accounts for those studies on the reactivity of palladium complexes bearing fluoride or fluorinated groups that allow to rationalize why some catalysts are effective and why some others are not. Although progress in the understanding of these chemical systems has been enormous in recent years, many aspects of their reactivity are still poorly understood, so, predictably, the field will remain an active focus of research in coming years.

In Situ Generation of ArCu from CuF2 Makes Coupling of Bulky Aryl Silanes Feasible and Highly Efficient.

A bimetallic system of Pd/CuF2, catalytic in Pd and stoichiometric in Cu, is very efficient and selective for the coupling of fairly hindered aryl silanes with aryl, anisyl, phenylaldehyde, p-cyanophenyl, p-nitrophenyl, or pyridyl iodides of conventional size. The reaction involves the activation of the silane by Cu(II), followed by disproportionation and transmetalation from the Cu(I)(aryl) to Pd(II), upon which coupling takes place. Cu(III) formed during disproportionation is reduced to Cu(I)(aryl) by excess aryl silane, so that the CuF2 system is fully converted into Cu(I)(aryl) and used in the coupling. Moreover, no extra source of fluoride is needed. Interesting size selectivity towards coupling is found in competitive reactions of hindered aryl silanes. Easily accessible [PdCl2 (IDM)(AsPh3)] (IDM = 1,3-dimethylimidazol-2-ylidene) is by far the best catalyst, and the isolated products are essentially free from As or Pd (<1 ppm). The mechanistic aspects of the process have been experimentally examined and discussed.

Revealing the diastereomeric nature of pincer terdentate nitrogen ligands 2,6-bis(arylaminomethyl)pyridine through coordination to palladium

Palladium complexes of formula [PdLCl]X (X = Cl 1, BF42) containing the pincer terdentate ligands L [L = 2,6-(ArNHCH2)2C5H3N (Ar = 4-MeC6H41a and 2a, 4-MeOC6H41b and 2b); L = 2,6-(4-MeC6H4NMeCH2)2C5H3N 1c and 2c] have been synthesised as cis–trans diastereomeric mixtures. The chiral nature of both amine arms of the pincer ligands accounts for the mixtures of isomers. All the complexes show dynamic behavior assigned to conversion between diastereomers. A ΔG‡273 of 68.9 kJ mol−1 for 2a and a ΔG‡273 of 65.8 kJ mol−1 for 2c were found through complete DNMR line-shape analysis of the –CH2– signals in the 1H spectra. The cis–trans conversion requires the inversion of the pyramidal nitrogen of one of the coordinated amine arms. Two putative pathways have been proposed for such inversion: a) dissociation of one of the amine nitrogen atoms followed by inversion of the nitrogen atom and reformation of the nitrogen–palladium bond and b) deprotonation of one of the N–H bond leading to an amido intermediate which can reprotonate on the other side. Experimental evidence is given for both mechanisms. The structural characterization of 1a is described.