Direct Cyclopalladation of Fluorinated Benzyl Amines by Pd3(OAc)6: The Coexistence of Multinuclear Pdn Reaction Pathways Highlights the Importance of Pd Speciation in C–H Bond Activation

Palladacycles are key intermediates in catalytic C–H bond functionalization reactions and important precatalysts for cross-couplings. It is commonly believed that palladacycle formation occurs through the reaction of a substrate bearing a C–H bond ortho to a suitable metal-directing group for interaction with, typically, mononuclear “Pd(OAc)2” species, with cyclopalladation liberating acetic acid as the side product. In this study, we show that N,N-dimethyl-fluoro-benzyl amines, which can be cyclopalladated either ortho or para to fluorine affording two regioisomeric products, can occur by a direct reaction of Pd3(OAc)6, proceeding via higher-order cyclopalladated intermediates. Regioselectivity is altered subtly depending on the ratio of substrate:Pd3(OAc)6 and the solvent used. Our findings are important when considering mechanisms of Pd-mediated reactions involving the intermediacy of palladacycles, of particular relevance in catalytic C–H bond functionalization chemistry.


■ INTRODUCTION
The cyclopalladation of substrates bearing a suitable metaldirecting group and a proximal C−H bond, e.g., N^CH, at "Pd(OAc) 2 " is a commonly encountered reaction in both the synthesis of palladacycles and catalytic C−H functionalization processes (Figure 1). 1 Moreover, such palladacycles are invoked as key intermediates, either on-or off-cycle, for many different types of reactions. 2Palladacyclic products can be mononuclear, dinuclear, or trinuclear (vide supra).In most studies, cyclopalladation is thought to occur via a mononuclear Pd II species (Figure 1), with the general presumption that despite the form of the "Pd(OAc) 2 " starting material used, i.e., Pd 3 (OAc) 6 or polymeric [Pd 2 (OAc) 4 ] n 3 species, mononuclear "Pd(OAc) 2 " is delivered in solution for direct reaction with the N^CH substrate.However, the occurrence of palladacyclic products in dinuclear or trinuclear forms raises the question of whether C−H bond activation takes place through polynuclear Pd species, or if the mononuclear Pd complexes aggregate by alternative mechanisms (the latter being the current state of thinking). 4ranell et al. 5 proposed that primary benzylamines undergo cyclopalladation involving dinuclear Pd II species in a cooperative manner, where the metalation by the first palladium atom is the rate-limiting step.Furthermore, Musaev et al. showed that a single monoprotected amino acid (MPAA)-bridged dipalladium core [Pd 2 (MPAA) 1 ] is an active catalyst for cyclopalladation of N,N-dimethylaminomethylferrocene. 6igure 1.Top: cyclopalladation of suitable substrates bearing a metaldirecting group (depicted here with nitrogen); "Pd(OAc) 2 " can be derived from different palladium(II) diacetate sources, e.g., Pd 3 (OAc) 6 or [Pd 2 (OAc)  4 ] n (less commonly).Bottom: cyclopalladation of 1a to give regioisomeric products 2a 6 (para) and 2a 2 (ortho), as reported by Fairlamb and Perutz et al. (note that the palladacyclic numbering system is that used in the paper). 10omputational studies reported by Musaev and coworkers pointed to the direct reaction of liberated "Pd 2 (OAc) 4 " from Pd 3 (OAc) 6 , which is arguably the most common commercially used palladium(II) acetate source (note: at the time of writing, Pd 3 (OAc) 6 is the only "Pd(OAc) 2 " source openly available). 3,7hile thermodynamically uphill in terms of compound isolation, coordination of a suitable N^CH substrate allows formation of stable intermediates providing a competing pathway for cyclopalladation via the dinuclear Pd II "Pd 2 (OAc) 4 " species.Despite this possibility, the consensus is that cyclopalladation proceeds predominantly via mononuclear Pd II intermediates.
On the other hand, Yu et al. 8 invoked reactions of oxazolines with Pd 3 (OAc) 6 to give a trinuclear Pd II species containing two N-coordinated oxazoline ligands, which undergo monomerization prior to cyclopalladation occurring; formation of mononuclear palladacycles then aggregates to bring about the formation of trinuclear [C^NPd(μ 2 -OAc) 2 Pd(μ 2 -OAc) 2 Pd(C^N)] species, which have been observed in other studies.For example, Vańǎ et al. established that cyclopalladation can occur directly at Pd 3 (TFA) 6 with acetanilide liberating dinuclear cyclopalladated complexes, "Pd(TFA) 2 ", and carboxylic acid. 9he cyclopalladation of a series of fluorinated benzyl amines with Pd 3 (OAc) 6 was reported by Fairlamb et al. 10 For N,Ndimethyl-3-fluorobenzyl amine 1a (Figure 1), cyclopalladation was found to be nonselective in CH 3 CN, affording regioisomeric dinuclear [Pd(C^N)(OAc)] 2 products 2a 6 and 2a 2 .Cyclopalladation involving palladium chloride salts, proceeding via a different mechanism, was regioselective placing the fluorine substituent para to Pd II .A question from that study was whether cyclopalladation of the higher-order Pd 3 (OAc) 6 cluster might also take place, which was mentioned in the concluding remarks to that study.
In this paper, we report the outcomes of the direct reactions of fluorinated benzyl amines with the cyclic Pd 3 (OAc) 6 cluster, under varying reaction conditions.Reaction monitoring by NMR spectroscopic analysis shows the formation of different Pd II species, including formation of both trinuclear and dinuclear Pd II species.Our studies indicate that a direct cyclopalladation of N,N-dimethyl-4-fluorobenzyl amine 1b with Pd 3 (OAc) 6 occurred under conditions where there is "excess" Pd over 1b, resulting in formation of trinuclear clusters of the type [C^NPd(μ 2 -OAc) 2 Pd(μ 2 -OAc) 2 Pd-(C^N)].Furthermore, we reveal a changing regioselectivity in certain substrates.

■ RESULTS AND DISCUSSION
Influence of the Solvent.We first assessed whether the regioselectivity for cyclopalladation of 1a with Pd 3 (OAc) 6 was altered with changing solvent nature (Figure 2 and Table S1, see the Supporting Information).Thus, we conducted the reaction of 1a (1.3 equiv with respect to Pd) with Pd 3 (OAc) 6 in different solvents and analyzed (by NMR) the ratio of cyclopalladated products before and after addition of pyridine.The addition of pyridine enables simplification of spectra due to the cleavage of polynuclear complexes and formation of mononuclear complexes of the type trans-[C^NPd(OAc)(Npyridine)]. 10 The results displayed in Figure 2 and Table S1 show an increasing amount of the ortho activated product 2a 2 with increasing dielectric constant.It is also pertinent to mention that no temperature effect is observed in two exemplar solvents, namely, toluene and acetonitrile (Table S2, see the Supporting Information).
The reaction outcomes described in Figure 2 can be explained in part by the findings of Lei and coworkers, 11 who showed that monomerized trans-Pd(OAc) 2 (solvent) 2 is liberated from Pd 3 (OAc) 6 in more polar solvents (evidenced by in operando X-ray absorption spectroscopy).
These data show that solvent polarity lowers the energy for the ortho-palladation reaction pathway.In less polar solvents, we expect larger Pd clusters to be dominant, mainly as the solvent is less able to displace the bridging Pd-acetoxy ligands.Thus, the presence of large Pd clusters disfavors the orthopalladation reaction pathway.We cannot rule out changes in character at the nitrogen center influencing transition state structures and geometries.
Influence of Reaction Stoichiometry.The influence of the reaction stoichiometry on cyclopalladation regioselectivity was next assessed (Table 1).In chloroform (1% EtOH), the ratio of regioisomers 2a 6 and 2a 2 remained constant while changing the molar ratio of 1a versus "Pd(OAc) 2 ".In contrast, in dichloromethane and acetonitrile, changes in the ratio of 2a 6 and 2a 2 on lowering the amount of 1a were observed (Table 1 and Table S3).
The deeper insight into this difference offers comparison of the 19 F{ 1 H} NMR spectra of the individual experiments measured before addition of pyridine (Figure 3).From the spectral data for experiments run in chloroform, only the signals of dinuclear palladacycles 2a 6 and 2a 2 are present.Influence of the solvent on the ratio of regioisomers 2a 6 and 2a 2 .Red points are included with some degree of uncertainty.For more details, see Table S1.This observation is consistent with the changes observed in Table 1 and can be explained by the opening of a new reaction pathway involving alternative polynuclear reaction intermediates, affording a different ratio of ortho-and para-substituted palladacycles.This reaction pathway becomes more important with an increasing ratio of palladium(II) acetate in the reaction mixture.
Kinetic Experiments.To gain further information about the reaction pathways and intermediates, the kinetic behavior of the system was monitored by 1 H and 19 F{ 1 H} NMR spectroscopic analysis.To avoid the complicated spectra due to the presence of regioisomeric species, N,N-dimethyl-4fluorobenzyl amine 1b was used as a substrate in the first instance (Scheme 1).
The temporal evolution of intermediates and products is visible by 19 F{ 1 H} NMR spectral analysis (Figure 4).Here, the reaction containing a small excess of 1b (1.3 equiv) over "Pd(OAc) 2 " showed signals of six reaction species (intermediates 3b, 4b, 5b, and 6b and products 2b and 8b) grouped into two spectral regions (Figure 4).The species seen in the region between δ −112 and −114.5 ppm correspond to the signals of fluorine atoms connected to the N-coordinated non-C−H activated substrate.On the other hand, in the region of δ −116.5 to −118 ppm are found the fluorine atoms connected to the cyclopalladated species.
The product/intermediate evolution profiles obtained by integration of the individual 19 F{ 1 H} NMR signals are depicted in Figure 5.It is shown that each reaction species contains only one type of substrate (likely N-coordinated, cyclopalladated).The only exception is 6b, containing both N-coordinated (nonactivated, "non") and cyclopalladated (activated, "act") substrate molecules.
The kinetic behavior of solutions containing a different excess of "Pd(OAc) 2 " over 1b was also examined.Changes were noted in these experiments (Figure 5 and Figures S3− S18, Supporting Information).Firstly, signals corresponding to the second product 8b and intermediates 7b and 9b whose abundance increased with a decreasing 1b/Pd ratio of reactants appear.While 7b gives one signal in the region of N-coordinated substrates, 9b gives at least five weak signals in both regions of the spectra, indicative of the presence of cyclopalladated and N-coordinated units within the molecule.Secondly, we note that 3b grows in the presence of an increasing excess of 1b.
The knowledge gained from the reaction profiles obtained by 19 F NMR spectroscopic analysis can help to extract analogous 1 H spectral data, enabling assignment of the acetate ligands to the reaction species (see Figures S3−S7 and S13− S17, Supporting Information).The problematic region is that in the range of 1.8−2.1 ppm in the 1 H NMR spectra, where there are overlapping signals of N−CH 3 and acetate CH 3 groups.
Signal Assignment.The signals for unreacted 1b are observable only in the experiment where there is an excess (Figures S7 and S17, see the Supporting Information), as singlets with variable chemical shifts due to an interaction with liberated acetic acid. 12he 19 F signal of the dinuclear product 2b appears at δ −116.9 ppm. 1 H NMR exhibits signals for the aromatic protons at δ 6.92 (1H) and 6.75 (2H) ppm.These are accompanied by two "doublets" of diastereotopic benzylic CH 2 groups at δ 3.65 (1H) and 3.25 (1H) ppm together with two distinctive N−CH 3 groups at δ 2.82 (3H) and 2.16 (3H, NCH 3 ) and a bridging acetate methyl group at δ 2.11 (3H) ppm.These data are characteristic of palladacyclic complexes. 13rinuclear products 8b give signals at δ −117.60 and −117.62 ppm by 19  We note that the formation of products 2b and 8b is accompanied by formation of liberated acetic acid δ 2.15 (3H).S3 and related comments).

Organometallics
The first two intermediate species 3b and 4b give rise to signals for an N-coordinated substrate.Furthermore, the benzylic CH 2 and N−CH 3 protons are not split, indicating that the substrate units are not bonded tightly, i.e., the complexes are not held in a rigid conformation or alternate configuration.Intermediate 3b gives one signal at δ −113.9 ppm by 19 F NMR.The corresponding 1 H signals at δ 3.66 (2H−CH 2 ) and 2.33 (6H−N(CH 3 ) 2 ) ppm are not coupled to other nuclei.Aromatic protons are found at δ 7.87 (2H) and 7.19 (2H) ppm.The 1 H signal at δ 1.95 ppm (3H) corresponds to the acetate CH 3 groups.The abundance of 3b is increasing with increasing excess of 1b over Pd.Complex 3b is most likely mononuclear Pd(OAc) 2 (1b) 2 whose formation is proposed in the first steps of the reaction of Pd 3 (OAc) 6 with a stoichiometric amount of benzylamine 5 or a two-fold excess of dimethylbenzylamine. 14 The fluorine chemical shift of 4b ( 19 F NMR) appears at δ −114 ppm.Signals at δ 8.35 (2H−ArH), 7.35 (2H−ArH), 3.56 (2H−CH 2 ), 2.36 (6H), and 1.91 ppm (3H) in 1 H were also assigned to 4b.The relative abundance of this intermediate seems to be almost independent of the 1b/Pd ratio.However, it strongly increases after addition of water to the reaction mixture (Figure S19).We were not able to fully assign its structure and nuclearity; however, it contains Pd/1b/ OAc in a 1:1:1 ratio; we tentatively suggest that it is a Pd 2 dimer complex possessing bridging hydroxo ligands.
If the reaction occurs with excess "Pd(OAc) 2 ", signals of new but minor intermediates 7b and 9b, together with two signals of products 8b, appear (Figure 3).Their occurrence is concominant with increasing the Pd:1b ratio.Unfortunately, due to their lower abundance and overlap with other signals, assignment of all the signals was not possible by 19 F NMR spectroscopic analysis; structural deductions were thus made by comparison with dinuclear Pd 2 species.
Complex 7b provides only one signal for the N-coordinated species at δ −112.6 ppm ( 19 F NMR). Signals at δ 7.39 (2H− Ar), 4.40 (1H), and 2.78 (3H) ppm were identified by 1 H NMR spectroscopic analysis.These data taken together point to this being a trinuclear analogue of 5b.Slow evaporation of the solvent from a reaction mixture starting with excess Pd 3 (OAc) 6 over 1b gave crystals suitable for crystallographic analysis.The results indicate the presence of a cocrystal of both products 2b and 8b (Figure 6).This additional characterization provides additional confirmation of our structural assignments by NMR spectroscopic analysis (in solution).As far as we know, cocrystallization of this kind is unique in the chemistry of palladium(II) carboxylates, and only a few clusters 15 or polymers 16 containing more than four palladium atoms and a carboxylate group are known.On the other hand, there are approximately 20 examples of trinuclear Pd analogues 8,17 of 8b.Meanwhile, in 8b and the aforementioned examples, three palladium atoms bridged by four acetates are arranged linearly with separations of 3 Å, where planes between the acetate ligands of neighboring palladium atoms are perpendicularly oriented.About a quarter of the reported structures exhibit other features, e.g., three palladium atoms are bridged by less than four carboxylates and thus exhibit shorter separations or a bent structure. 18Four oxygen atoms around Pd4 in 8b (Figure 6) are situated in a perfectly planar arrangement, completed by symmetry-related Pd3 atoms in a tetragonal bipyramid.In the case of the coordination polyhedra of Pd3 atoms, the situation is more complicated.Four heteroatoms of the ligands surrounding the Pd3 centers are partially distorted in the square plane of the metal, found 0.019(2)Å below the plane made by heteroatoms toward the Pd4 direction.The C23−Pd3−Pd4 angle is 117.40(12)°, a significant deviation from 90°.While there are typical weak noncovalent interactions, there is no significant connectivity between trinuclear and dinuclear molecules.There is a plethora of dinuclear palladium carboxylates from which about 20 structures contain a derivative of 2-[(N,N-dimethylaminoethyl)phenyl]-type ligands.There appears to be no major difference in these structures characterized by the square planar arrangement of the heteroatoms around palladium and relatively short interactions between metals of ∼3 Å. 4g,10,19 The planes of the carboxylates are nearly perpendicular, with ligands occupying the remaining two coordination sites with an alternate arrangement.Ligand substitution has a negligible influence on the intramolecular N−Pd interaction, being ∼2 Å.The presence of fluorine atoms, especially in the ortho-and parapositions (6 and 4), in relation to palladium causes a bigger deflection of phenyl planes away from the ideal parallel orientation.For example, the interplanar angle in the unsubstituted ligand is 12.35(11)°, 10 whereas the presence of fluorine in position 5 of 2b promotes a change to 33.18(19)°.Further difluorination 10 in positions 4 and 5 leads to an angle of 42.13(12)°.Alteration of the fluorine atoms, to either positions 3 and 6 or 4 and 6, widens the angles to 89.43 (19)  and 87.85(11)°, respectively.
With the knowledge gained about the reaction intermediates involving substrate 1b, we measured the kinetic behavior of the 3-substituted substrate 1a (a nonsymmetrical substrate) in CH 2 Cl 2 and CH 3 CN.The experiment shows analogous behavior and intermediates, as in the case of symmetrical substrate 1b (see Figure 7 and S22 − Supporting Information).

■ DISCUSSION AND CONCLUSIONS
We have shown that Pd 3 (OAc) 6 , which is a Pd cluster species, reacts with fluorinated substrates 1, for which there is a dependence on the stoichiometry of the species 3, 5, and 7 formed (Scheme 2).It is likely that 3 is formed first, which is then subsequently transformed into 5 or 7 while releasing one molecule of the unreacted substrate 1 (Figure 5, top left).However, alternative direct formation of 5 or 7 is possible, especially in the presence of higher quantities of palladium.In the presence of H 2 O (e.g., in the presence of adventitious moisture), 4 is formed.In specific terms relating to the fluorinated substrate 1b, on formation of 5b, it undergoes C− H bond activation to form 6b followed by a subsequent second C−H bond activation to afford 2b.To the best of our knowledge, this is the first time that a half-activated intermediate 6b has been evidenced experimentally.Furthermore, it has been determined that 9 derives from 7.
From the kinetic behavior (Figure 5), it was deduced that 7b reaches a maximum later than analogue 5b, and 9b later than analogue 6b.Furthermore, product 8b appears following the formation of 2b.We can state that the trinuclear Pd 3 (OAc) 6 cluster interacts first with substrates 1, which are subsequently broken down, fragmenting into mono-or dinuclear Pd species, from which the dinuclear Pd pathway can proceed (Scheme 2).However, in the presence of excess Pd, the dinuclear species reacts with Pd 3 (OAc) 6 , allowing the trinuclear intermediate 7b to be formed.Species 7b further undergoes two subsequent C−H bond activations within the trinuclear Pd framework via 9b in forming 8b.
There are several factors speaking against the most common hypothesis that C−H activation occurs exclusively via mononuclear Pd 1 species, while the polynuclear species are formed later.Firstly, the changes in the ratio of ortho and para activated products discussed above (see Figure 3 and Table 1) provide evidence that at least two of these pathways occur, while each of them takes place with a different preference for formation of ortho and para products.In agreement with experiments employing different solvents, the presence of large Pd clusters disfavors the ortho-palladation.Secondly, our data shows that the mononuclear pathway is slow (Figure S21, see the Supporting Information).If the reaction proceeds with more than one equivalent of 1b, the reaction rate significantly decreases.Thirdly, we have determined that 2b can be converted to 8b by addition of Pd 3 (OAc) 6 , over several hours  (note: we see no change after five minutes, see Figure S20, Supporting Information).However, this is slower in comparison to the reactions studied.Thus, this shows that intermediate 9b is kinetically relevant.
In conclusion, we have provided experimental evidence that cyclopalladation reactions can proceed via dinuclear and trinuclear Pd cluster/complexes, in addition to mononuclear Pd species.Our reaction outcomes suggest that cyclopalladation is slower for mononuclear Pd species, involving substrates such as 1 in a reaction with Pd 3 (OAc) 6 .Regioselectivities are subtly different, depending on the reaction pathway.These findings highlight that there is an added complexity in cyclopalladation reactions of palladium-(II) acetate with appropriate C−H substrates containing Pd-directing groups, a far-reaching finding with implications for catalysis and synthetic chemistry involving palladacyclic intermediates.

■ EXPERIMENTAL DETAILS
Influence of the Solvent.To the solution of 10 mg (0.045 mmol) of "Pd(OAc) 2 " in 0.5 mL of the solvent was added 8 μL (0.059 mmol) of 1a, and the reaction mixture was stirred at room temperature.After 5 h, the solvent was evaporated, and the residue was dissolved in CDCl 3 and analyzed by 1 H and 19 F protondecoupled NMR.Next, 4 drops of pyridine was added into the NMR tube, and the sample was analyzed again.
Influence of Reaction Stoichiometry.To 10 mg (0.045 mmol) of "Pd(OAc) 2 " was added 0.5 mL of the solvent (chloroform stabilized with EtOH 1%, acetonitrile, and DCM) followed by various We indicate the starting point as Pd 3 (OAc) 6 , which can be in equilibrium with dimer Pd 2 (OAc) 4 and monomer Pd(OAc) 2 species.We suspect that there are exchange processes involving water (and/or acetic acid).amounts (2, 4, 6, 8, and 12 μL) of 1a.The reaction mixture was stirred for 4 h at room temperature, the solvent was evaporated, and the residue was dissolved in CDCl 3 and analyzed by 1 H and 19 F proton-decoupled NMR.Next, 4 drops of pyridine was added into the NMR tube, and the sample was analyzed again.
Kinetic Experiments.Palladium acetate (10 mg, 0.045 mmol) was dissolved in an NMR tube in 0.55 mL of a deuterated solvent (CD 3 CN or CD 2 Cl 2 ).After measurement of the first spectra, 8, 5, 3, or 2 20 μL of 1b was added, and the 1 H and 19 F kinetics was followed.For the 2D experiments, the reaction mixture was cooled to −20 °C 7 min after initiation.
Crystal Growth.The cocrystal of 2b and 8b was prepared by the slow evaporation of a solution containing 20 mg (0.09 mmol) of "Pd(OAc) 2 " and 5 μL of 1b in 0.5 mL of DCM in a pentane atmosphere.The single-crystal X-ray diffraction data can be found deposited to the Cambridge Crystallographic Database Centre (CCDC 2189187).

■ ASSOCIATED CONTENT
* sı Supporting Information

Figure 2 .
Figure2.Influence of the solvent on the ratio of regioisomers 2a 6 and 2a 2 .Red points are included with some degree of uncertainty.For more details, see TableS1.

Figure 3 .
Figure 3.Comparison of 19 F{ 1 H} NMR spectra (measured in CDCl 3 ) illustrating product distribution dependence on reaction stoichiometry (different amounts of 1a added to the one equivalent of "Pd(OAc) 2 ") for experiments running in chloroform (1% EtOH) (top) and acetonitrile (bottom) (for details, see TableS3and related comments).
F signal occurs at δ −113.5 ppm.By 1 H NMR, there are signals indicative of para disubstitution at δ 8.25 (2H) and 7.27 (2H) ppm, two "doublets" at δ 4.53 (1H) and 3.72 (1H) ppm corresponding to a diastereotopic CH 2 , and four signals at δ 2.70, 2.22, 2.01, and 1.77 ppm of CH 3 groups derived from two N−CH 3 groups (substrate) and two CH 3 of the bridging acetate ligands at Pd.The splitting of CH 2 and N(CH 3 ) 2 groups, analogous to the splitting in the dinuclear Pd 2 product 2b, suggests an alternative chemical environment.The existence of this intermediate is likely rigid and in a dimeric form (Figure 5).The intermediate 6b gives two signals with identical intensities by 19 F NMR.One signal is in the region of an Ncoordinated moiety (δ −113.77ppm) and the second signal in the region for a palladacyclic motif (−116.5 ppm).The 1 H spectra show the presence of one nonactivated paradisubstituted aromatic ring with signals at δ 7.76 (2H) and 7.15 (2H) ppm, along with one activated aromatic ring with signals of three protons at δ 7.05 (1H), 6 Finally, 9b exhibits two fluorine signals at δ −113.77and −113.82 in the region of N-coordinated substrates and three signals at δ −117.34,−117.5, and −117.69 ppm in the region showing cyclopalladated substrates by19 F NMR spectroscopic analysis.This is most likely a trinuclear Pd 3 analogue of 6b.

Figure 6 .
Figure 6.X-ray structure of a cocrystal of 2b and 8b (image produced from the cif file in CrystalMaker X, version 10.8.1).Thermal ellipsoids are drawn at a 50% occupancy level.

Figure 7 .
Figure 7.Comparison of the evolution profiles obtained from 19 F{ 1 H} NMR for reaction of different amounts (1.31 top and 0.5 bottom equiv) of 1a with "Pd(OAc) 2 " (1 equiv) in CD 2 Cl 2 at room temperature.The signals of products 2a, 8a, and 9a are given for clarity.

Table 1 .
Influence of Reaction Stoichiometry on the Ratio of Regioisomers 2a 6 and 2a 2 However, the experiments in acetonitrile and dichloromethane exhibit a decreasing intensity of signals corresponding to dinuclear palladacycles 2a 6 and 2a 2 and increasing intensity of new signals, associated with increasing Pd present in the reaction mixture.