Alkyl(quinolin-8-yl)phosphine Oxides as Hemilabile Preligands for

Jun 23, 2014 - Anionic phosph(in)ito (“phosphoryl”) ligands: Non-classical “actor” phosphane-type ligands in coordination chemistry. P. Sutra ...
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Alkyl(quinolin-8-yl)phosphine Oxides as Hemilabile Preligands for Palladium-Catalyzed Reactions Yu-Chang Chang,† Wei-Chan Chang,† Chan-Yu Hu, and Fung-E Hong* Department of Chemistry, National Chung Hsing University, 250 Kuo-Kuang Road, Taichung 40227, Taiwan S Supporting Information *

ABSTRACT: Preligands of quinolyl-substituted secondary phosphine oxides (SPOs, 2a−d) were prepared and characterized. The unique palladium complex 3, having a distorted-square-pyramidal structure, was obtained from the reaction of 2 equiv of 2c with Pd(COD)Cl2 or [Pd(μ2-Cl)(η3allyl)]2. In the crystal structure of 3, an apical chloride ligand and a supramolecular tetradentate ligand composed of a deprotonated 2c′ and a neutral 2c′ were resolved (2c′: PA form of 2c). Intriguingly, the gas-phase optimized geometry of 3 converged to a distorted-square-planar structure, which was predicted by density functional calculations. The solid-state distorted-square-pyramidal structure of 3 can only be explained with the consideration of environmental effects (i.e., the electrostatic interactions between the surrounding molecules). As also evidenced by 31P NMR experiments performed in different deuterated solvents, the crystal structure of 3 is retained in solution. In the crystal structure of 3, a long Pd−Cl bond was analyzed by energy decomposition analysis, showing that the bond is dominated by electrostatic character. Furthermore, application of these SPOs using the Heck reaction shows good reactivity toward common aryl bromides. The hemilabile preligand 2c also tautomerizes to the competent ligand 2c′ for palladium-catalyzed three-component reactions.

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INTRODUCTION Ligands are of central importance in metal-catalyzed reactions.1 In general, ligands directly influence the performance of transition-metal catalysts through their electronic and steric effects.2 For instance, in cross-coupling reactions, the strong electron-donating capacity of the donor atom in a ligand set can expedite the rate of oxidative addition, while the bulkiness of substituents can accelerate the final step of reductive elimination and regenerate the kinetically stabilized monoligated catalyst.3 Indeed, the initial formation of the most active monoligated Pd0L species has been shown to originate from ligand dissociation of Pd0L2, and this can be promoted by using bulky ligands.3g,4 In addition, highly coordinatively unsaturated Pd0L complexes that are coordinated by bulk ligands have been shown to accelerate the oxidative-addition step for aryl halides.3c,g,i,5 Phosphines are conventionally categorized as spectator ligands, meaning that they stay intact and keep their coordination to a metal center during chemical reactions. Recently, the concept of actor ligands, which dissociate or participate in a chemical or catalytic reaction, has emerged for guiding ligand design.6 Note that both spectator and actor ligands can be either monodentate or multidentate. In addition, redox-active ligands,7 cooperative ligands,8 frustrated Lewis pair ligands,9 and hemilabile ligands7c,10 can behave as actor ligands. If a metal center can be coordinated by actor ligands, it would be interesting to examine the potential of the metal center to anchor the actor ligands, giving rise to ligand-based reactivity rather than metal-based reactivity. © XXXX American Chemical Society

An important strategy for designing hemilabile multidentate ligands, in particular bidentate ligands, is to incorporate at least two donor sites (donor atoms or π groups) with distinct electronic properties for metal coordination. According to Pearson’s principle of “hard and soft acids and bases (HSAB)”,11 the soft Pd(II) ion has a preference for ligands with a soft phosphorus atom rather than the hard nitrogen donor.12 Therefore, the incorporation of nitrogen and phosphorus atoms into a hybrid bidentate P−N ligand can result in a hemilabile ligand for soft Pd(0) or Pd(II) complexes. Figure 1 illustrates the operation of a hemilabile P−N ligand on coordination to a soft metal center during a catalytic reaction. The coordination and dissociation of the weak donor of the hemilabile ligand to palladium complexes have been shown to be effective toward the Suzuki−Miyaura reaction and also for isolating low-valent active palladium species.13

Figure 1. Illustration of the behavior of a P−N type hemibile ligand coordinated to a soft Pd(0) or Pd(II) center: rectangle, vacant site; S, donor ligand or reagent. Received: April 23, 2014

A

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Since the initial report published by Buchwald et al. in 1998,14 researchers have developed a sophisticated and efficient ligating system of stable monodentate biaryl phosphines for palladium-catalyzed coupling reactions even at room temperature for aryl chlorides.15 The biaryl phosphines have a strong phosphorus donor together with a potentially weak πcoordinated biaryl group16 and/or heteroatom donor decorated on the biphenyl substituent5e for stabilizing coordinatively unsaturated palladium intermediates. Recently emerging as air- and/or moisture-stable preligands,17 (heteroatom-substituted) secondary phosphine oxides ((HA)SPOs, R2P(O)H) have drawn much attention.18 SPOs are generally easy to synthesize,19 and their stability allows long-term preservation and convenient handling. Intriguingly, the tautomerization of an (HA)SPO to a (heteroatomsubstituted) phosphinous acid ((HA)PA, R2P−OH) in the presence of a transition-metal complex allows the (HA)SPO to act as a phosphine-like ligand (Figure 2).20 Importantly,

substituents on two respective monodentate ligands has been realized.24 The negative charge on PA-based supramolecular ligands can be used to supplement the charge on a metal complex (Figure 3). If the proton in PA-based anionic bidentate ligands in cis metal complexes is replaced with main-group metals,21q heterobimetallic cooperativity is noted between the two metal sites. Such heterobimetallic effects in cis complexes have been shown to be useful in C−F bond activation25 and Kumada− Corriu cross-coupling reactions,26 respectively. In this study, four unique quinolyl-substituted and SPObased hemilabile P−N bidentate ligands were synthesized (2a− d, Scheme 1). The strategy described herein is to simultaneously take advantage of both the stability of the SPO and the hemilability of the quinolyl substituent on the phosphorus atom (Figure 4a). Interestingly, an ambient-

Figure 2. Tautomerization of racemic secondary phosphine oxides (SPO) to phosphinous acids (PA) in the presence of a transition-metal species.

Figure 4. (a) Illustration of the potential operation of SPO-based hemilabile P−N bidentate ligands. (b) Intramolecular hydrogenbonded supramolecular tetradentate binding mode for PA-hemilabile ligands. [TM]: transition-metal fragment.

judicious application of (HA)SPO preligands to various crosscoupling reactions has illustrated the usefulness of (HA)SPOs.21 As a side note, the plausible chemical transformation between a diaminophosphine chloride and diaminophosphine oxide (N−P−N type HASPO) has been reported in the literature.21g,i,k,22 Noteworthy features of phosphinous acids (PA) are their divergent coordinating modes with various transition-metal species (Figure 3).23 Among the coordinating modes shown in Figure 3, the self-assembled supramolecular bidentate ligand can be obtained from two PAs through the formation of an intermolecular hydrogen bond initiated by the loss of a proton on one of the two P−OH groups. In recent work reported by Breit et al., the concept of designing supramolecular bidentate ligands by utilizing hydrogen-bond interactions between

temperature-stable and structurally unique square-pyramidal Pd(II) complex with a 2c′-based supramolecular tetradentate ligand was obtained (2c′ is the PA ligand form of SPO 2c), and its X-ray structure was also determined (thus, the three-in-one feature shown in Figure 4). Due to the long Pd−Cl bond length, 31P NMR and 1H NMR spectra were intentionally recorded in deuterated solvents with distinct polarity to clarify the ionic or covalent character of the resultant square-pyramidal Pd(II) complex. Density functional calculations were carried out to elucidate the bonding nature of the apical Pd−Cl bond in the Pd(II) complex. Finally, applications of these hemilabile ligands to the Heck cross-coupling reaction as well as the threecomponent catalytic reaction were investigated.

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RESULTS AND DISCUSSION Preparation of Quinolyl-Substituted Secondary Phosphine Oxide as Preligands (2a−d). The reactant, 8bromoquinoline, was synthesized on the basis of a procedure modified from that reported in the literature.27 Using 8bromoquinoline (1) as the starting material, several quinolylsubstituted secondary phosphine oxides, 2a−d, were prepared (Scheme 1). Initially, 6 mmol of 8-bromoquinoline was dissolved in 80 mL of THF in a round-bottom flask. The reaction temperature was lowered to −100 °C, and 1.2 mol equiv of tert-butyllithium in hexane was slowly added into the round flask. After the mixture was warmed to 0 °C, the reaction continued for another 15 min. Then, the reaction mixture was again cooled to −100 °C and the solution was added dropwise into 5 mL of a THF solution containing 5 mmol of RPCl2 (R = Ph (2a), Cy (2b), tBu (2c), iPr (2d)). In order to obtain the quinolyl-substituted phosphine chloride intermediate, the reaction mixture was stirred at 25 °C for 4 h. After the solution was cooled to 0 °C, the second intermediate of

Figure 3. Plausible coordination modes of SPOs toward transition metals. B

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Scheme 1. Preparation of Quinolyl-Substituted SPOsa

Cl)(η3-allyl)]2, the PA form of 2c′ could have revealed its chelate effect on 3.28 Crystal Structure of 3. The crystal structure of 3 bearing a divalent low-spin d8 Pd(II) center shows that the chloride ligand occupies the apical position of a distorted square pyramid in which the basal atoms consist of P(1), P(2), N(1), and N(2) (Figure 5a). This (distorted or pseudo) squarepyramidal geometry is rare for Pd(II) complexes.29 The distance between Pd and the mean plane constituted by the four basal atoms is 0.44 Å. Furthermore, the Pd−Cl bond distance is 2.7403(7) Å, which is within the sum of van der Waals radii of Pd and Cl (3.38 Å).30 However, the Pd−Cl bond distance resides near the upper bound of Pd−Cl bond lengths31 that have been archived in the Cambridge Structural Database (CSD).32 In addition, the Cl− is not in the ideal apical position of a perfect square-pyramidal geometry. Instead, the tilt angle between the Pd−Cl vector and the mean plane of P(1)−P(2)− N(2)−N(1) is 72.0°. In the CSD, only four distorted-squarepyramidal Pd(II) complexes with exceptionally long Pd−Cl bonds ranging from 2.796 to 3.106 Å were found.33 Moreover, two quinolyl groups flip in an opposite direction due to the very bulky tBu groups attached on phosphorus atoms and the repulsion between ortho hydrogens on quinolyl substituents (Figure 5b). In comparison with the spatial arrangements of quinolyl substituents in the crystal structures of Pd(Ph2Pqn)2Cl2, Pd(Ph2Pqn)2Br2, [Pd(Ph2Pqn)2Br]Br,29d and cis-[Pd(Me2Pqn)2](BF4)2,34 the two quinolyl rings flip toward the same direction so as to position the ortho hydrogens on two quinolyl substituents pointing upward and downward. Note that in cis-[Pd(Me2Pqn)2](BF4)2 the steric hindrance of Ph and Me substituents is smaller than that of tBu groups in 3. The Pd(II) center of 3 can be regarded as being coordinated by a hydrogen-bonded supramolecular tetradentate ligand composed of a deprotonated 2c′ molecue and a 2c′ molecule (Figures 4b and 5a). In comparison with trialkyl- or triarylphosphines, this type of bonding mode for phosphine and phosphite ligands is a unique phenomenon for PA ligands. The O(1)−H(1A) and O(2)−H(1A) distances are 1.29(5) and 1.14(5) Å, respectively. Moreover, the P(1)−O(1) and P(2)− O(2) bond distances are 1.548(2) and 1.558(2) Å, respectively. Heyrovska has demonstrated that the O−H, P−O, and PO bond distances are 1.04, 1.59, and 1.52 Å, respectively.35 Therefore, in the solid state, the noncovalent hydrogen-bond interaction could be interpreted as originating from the interaction between the molecular fragments P(1)−O(1)−··· H(1A)−O(2)−P(2). As evidenced from the Pd−N(2) and Pd−N(1) bond lengths (2.247(2) and 2.209(2) Å), the deprotonated and formally negatively charged 2c′ containing the P(1)−O(1)− moiety has a stronger trans influence on Pd− N(2) than 2c′ comprising the P(2)−O(2)−H(1A) fragment on Pd−N(1). Structure of 3 in Solution. As revealed in the crystal structure of 3, the Pd−Cl distance is exceptionally long. Since 3 does not dissolve well in toluene, tetrahydrofuran, or acetonitrile, the 31P NMR and 1H NMR experiments were carried out in dichloromethane-d2, chloroform-d, or methanold4 (Figure 6). Because the chemical shifts depend strongly on the molecular structures,29d,36 the NMR chemical shifts of 3 observed in deuterated solvents with various polarities can be employed to determine if the Pd−Cl bond in 3 is predominantly covalent or ionic. In three deuterated solvents, the corresponding 31P NMR chemical shifts for 3 are at 111.4,

a

Abbreviations: Ph, phenyl; Cy, cyclohexyl; tBu, tert-butyl; iPr, isopropyl.

quinolyl-substituted phosphine chloride was hydrolyzed using K2CO3(aq) for an additional 3 h. Finally, the designated quinolyl-substituted SPO was obtained after workup and column chromatography. Synthesis of 3. In the reaction of 2 equiv of SPO preligand 2c with Pd(COD)Cl2 at 25 °C for 12 h, 3 was obtained in 92% yield (Scheme 2). Its structure was determined by X-ray Scheme 2. Preparation of 3 from Pd(II) Complexes

Figure 5. (a) Illustration of the potential operation of a SPO-based hemilabile P−N bidentate ligand. (b) Hydrogen-bonded supramolecular tetradentate binding mode of SPO-hemilabile ligands. [TM]: transition-metal fragment.

diffraction methods (Figure 5a). In comparison to the 31P NMR chemical shift at 36.7 ppm for 2c, the chemical shift for 3 appears at 111.9 ppm. This indicates the typical downfield shift from the free phosphine ligand to a phosphine-coordinated palladium complex. Complex 3 is quite stable in solution and in the solid state. In 3, a deprotonated PA form of 2c′ and neutral 2c′ are self-assembled with the formation of an intramolecular hydrogen bond via the coordination to Pd(II) center, giving rise to a 2c′-based supramolecular tetradentate ligand in 3. Alternatively, as judged from the 31P NMR spectra, 3 can be quantitatively obtained from the reaction of 2 equiv of SPO 2c with [Pd(μ2-Cl)(η3-allyl)]2. According to the formation of 3 from the reaction of SPO 2c and Pd(COD)Cl2 or [Pd(μ2C

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4.7113, 8.9300, and 32.6130, respectively) was also incorporated for investigating the medium effects on the molecular geometry of 3. Only the electrostatic interaction is considered in the PCM solvation model. The crystal structure of distortedsquare-pyramidal 3 was used as the initial structure for geometry optimization. In the gas phase, a distorted-squareplanar geometry was obtained (Figure 7a). In solution, the

Figure 6. 1H NMR and 31P NMR chemical shifts of 2c in chloroformd (a) and 3 in dichloromethane-d2 (b), chloroform-d (c), and methanol-d4 (d).

Figure 7. G09/ωB97X-D-optimized (a) four-coordinate distortedsquare-planar complex in the gas phase and (b) five-coordinate distorted-square-pyramidal complex. Solvation effects of dichloromethane were considered during the geometry optimization.

111.9, and 111.7 ppm (right-hand side in Figure 6b−d). Additionally, the invariance of 31P NMR chemical shifts is also envisioned from the space-filling model of 3 (Figure 5b), in which two phosphorus atoms are buried by the surrounding atoms. For the 1H NMR chemical shifts, the doublet peak originating from JP−H coupling in the 1H NMR spectrum detected in chloroform-d disappeared upon coordination to the palladium fragment (Figure 6a versus Figure 6c). This is an indication of SPO-to-PA tautomerization in the presence of palladium species. In comparison with the chemical shift of two ortho-Ha atoms of free ligand 2c measured in chloroform-d, the signal of the ortho-Ha atome of 3 is shifted downfield by about 0.64 ppm in both dichloromethane-d2 (Figure 6b) and chloroform-d (Figure 6c). The downfield chemical shift of ortho-Ha can be attributed to the coordination of quinolyl rings to Pd(II) and also to the deshielding effect from the neighboring aromatic quinolyl rings (Figure 5b). Furthermore, the 1H NMR chemical shifts for the two chemically equivalent quinolyl rings in 3 are similar in dichloromethane-d2 and chloroform-d but not in methanol-d4 (left-hand side in Figure 6b−d). In view of the 1H NMR chemical shift for ortho-Ha of free ligand 2c in methanol-d4 at 8.95 ppm, the chemical shift for two ortho-Ha atoms of 3 is 9.44 ppm. These two ortho-Ha atoms of 3 also show a downfield shift by around 0.50 ppm in methanol-d4. The increased solvent sensitivity of the 1H NMR chemical shift of ortho-Ha in comparison to that for the 31P NMR counterparts is a result of the direct exposure of hydrogen atoms to the solute−solvent boundary shown by the space-filling model (Figure 5b). Therefore, the invariance of the 31P NMR resonance (Figure 6b−d) indicates the bonding nature of the Pd−Cl bond in 3, and the downfield shift of the1H NMR peak for the two orthoHa atoms in comparison to that for 2c denotes the coordination of two quinolyl rings. On the basis of the 31P NMR and 1H NMR spectra, the structure of 3 has a distorted-squarepyramidal geometry in dichloromethane, chloroform, and methanol solution. DFT Studies on the Structure of 3. ωB97X-D was employed for geometry optimization. In addition to optimization of the gas-phase geometry, the PCM solvation model for chloroform, dichloromethane, and methanol solution (ε =

distorted-square-pyramidal geometry was optimized (Figure 7b). Interestingly, the geometries optimized by B3LYP, B3LYPD3(BJ), M06-L, and M06 were qualitatively the same both in the gas phase and in solution. In the gas-phase optimized structure (Figure 7a), the distorted-square-planar geometry is related to the delicate balance of short-range repulsions between the dissociated quinolyl ring and the tBu group on the P(2) atom as well as between the two tBu groups on P(1) and P(2) (cf. Figure 5b). This distortion can also be seen from the Pd...N(2) distance of 2.833 Å. The short range of Pd···N(2) could allow recoordination of the quinolyl ring to the palladium center. In other words, the free rotation of the dissociated quinolyl ring is prohibited. In the solution phase where the five-coordinate square-pyramidal structure is preferred, the hemilability of two SPO-based P−N ligands in 3 is confined by their intramolecular steric hindrance (Figure 5b). Therefore, 3 is a stable complex under ambient conditions. The inconsistency between the (experimental or theoretical) gas-phase geometry and the solid-state crystal structure is likely because there are crystal-packing effects or environmental effects operating in the solid state.37 The gas-to-solid geometric discrepancy is normally found in molecules with weak bonds and large molecular dipole moments. In previous theoretical studies, solvation effects (i.e., the structureless continuum dielectric medium described by the continuum-solvation model) have been successfully employed to qualitatively or quantitatively simulate the crystal-packing effects for weakly bonded donor−acceptor compounds with large dipole moments.38 Moreover, when the gas-phase optimized molecular structure of the dimer or tetramer is compared with the corresponding crystal structure, it has been found that the structural parameters determined for the molecular crystal can be significantly recovered when the environmental effects are properly considered.39 Consequently, electrostatic polarization plays a role among other intermolecular forces in a molecular solid and can be properly modeled with the continuum solvation model.40 Physically, the idea lies in that the nearest-neighboring molecules tend to pack in a crystal such that the local D

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the weakened Pd−N(2) bond provides the driving force for the geometric relaxation from the condensed-phase distorted square pyramid to the gas-phase distorted square plane. Although the recovery of the crystal structure from the geometry optimization of 3 in dichloromethane, chloroform, and methanol might be fortuitous, environmental effects or more specifically the electrostatic interactions indeed have an impact on the structural parameters. According to ligand field theory, the five d-type molecular frontier orbitals should be split into four sets, b2 (dxy), e (dxz, dyz), a1 (dz2), and b1 (dx2−y2), for a square-pyramidal transitionmetal complex of C4v symmetry (Figure 9).43 While the five-

dipole−dipole interactions can be maximized among the molecular sites (the so-called “dipolar enhancement” mechanism).37a,c In other words, it is the representation that a molecule is solvated by other same nearest-neighboring molecules in which the ε value of a homogeneous solid constituted of same specific molecules could be approximately estimated.41 It has been shown that the optimized structure quickly converged to the crystal structure with an increase in the ε value. More recently, an elegant QM/MM approach that uses the electrostatic embedding scheme has been demonstrated to effectively reproduce the solid-state molecular structures and properties even for transition-metal complexes.42 In the unit cell of 3, the Pd−Cl bonds in two molecules are packed in an antiparallel manner. Prominently, the packing mode corresponds well to the dipolar enhancement mechanism of maximizing the dipole−dipole interaction in the condensed state. When the molecular dimer was used as the initial structure for gas-phase geometry optimization at the G09/ ωB97X-D level, the distorted-square-pyramidal structure was maintained (Figure 8). The calculated dipole moment of 0.7 D

Figure 9. (a) The five d orbitals in a square-pyramidal transition-metal complex with C4v molecular symmetry. (b) a1 molecular orbital of a five-coordination metal complex with 90° < θ < 120°.43

coordinate 3 (d8-Pd(II)) simply does not belong to C4v symmetry, one can reference the d-orbital splitting diagram of an idealized square-pyramidal transition-metal complex for understanding the bonding situation of 3. Energy decomposition analysis (EDA) was carried out at the ADF/ZORA/ B3LYP-D3(BJ) level of theory in conjugation with the linear combination of fragmental orbitals of Cl− and the remaining Pd fragment as the basis set (TZ2P/TZP quality). Figure 10 shows Figure 8. Gas-phase optimized molecular dimer. The dimer structure in the unit cell of 3 was used as the initial structure (G09/ωB97X-D results).

also agrees with the dipolar enhancement mechanism. By comparison of the ωB97X-D-optimized dimer structure with the crystal structure of 3, the distances from palladium to the mean plane of four basal coordinated atoms are 0.433 Å (0.431 Å) and 0.442 Å and the dihedral angles P(1)−P(2)−N(2)− N(1) are 3.78° (0.24°) and 1.77(5)°. The corresponding bond length differences for Pd−Cl bonds are 2.770 Å (2.766 Å)/ 2.7403(7) Å; the bond length deviations of five Pd-to-ligand distances are within 0.045 Å. Moreover, the Cl−Pd−P(1) and Cl−Pd−P(2) bond angles are 117.12° (114.62°)/116.41(2)° and 110.53° (112.27°)/112.78(2)° and the Cl−Pd−N(1) and Cl−Pd−N(2) bond angles are 89.13° (90.13°)/88.99(5)o and 88.14° (87.77°)/88.01(5)° for the optimized/X-ray structures, respectively. The successful reproduction of the crystal structure of 3 from the dimer approach, which was previously adopted by Frenking et al.,39a once again indicates the importance of dipole−dipole interactions in stabilizing the solid-state geometry. As discussed previously, the crystal structure of 3 can be qualitatively reproduced with the consideration of environmental effects (Figures 7b and 8). The gas-to-solid geometric discrepancy could be related to the long Pd−Cl bond as well as the large molecular dipole moment of 3 in the distorted-squarepyramidal geometry (μ = 9.6 D: single-point calculations for the crystal structure at the ADF/ZORA/B3LYP-D3(BJ) level as discussed below). More importantly, as a result of the strong trans influence of the P(1)R2−O(1)− moiety, the presence of

Figure 10. HOMO of 3 (isocontour value 0.03 au). Single-point calculations were carried out for the X-ray structure of 3 at the ADF/ ZORA/B3LYP-D3(BJ) theory level.

the a1-like HOMO obtained from single-point calculations using the crystal structure of 3. In the HOMO of 3, the σdonating atomic orbital of the apical Cl− ligand is apparently a filled 2pz atomic orbital (51.5%), and the σ-accepting orbital of the Pd fragment mainly consists of the mixing of dz2 and dyz atomic orbitals of Pd(II) in an antibonding manner. Therefore, the long Pd−Cl bond is attributed to the strong antibonding character in the HOMO between d8-Pd(II) and Cl− ligand (Figure 10). With the supposition that the crystal structure of 3 is at a local minimum, the EDA analysis concerning the Pd−Cl bond is illustrated in Table 1. The largest interaction is from ΔEelst (72.3%) among the stabilizing energies of quasi-classical electrostatic attraction (ΔEelst), orbital interaction (ΔEoi), and interfragmental dispersion energy (ΔEdisp). ΔEelst is about 3E

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mmol of K2CO3 instead of Cs2CO3 was used as the base (entry 4). In the Heck reaction, the base plays multiple roles. One of the functionalities of the base is to expedite the release of HX in the reductive elimination process, thus improving the speed of the overall catalytic cycle. With 2c as preligand, the screening of bases was pursued (Table S2 (Supporting Information)). Among all the bases examined, Cs2CO3, K2CO3, and CsF in DMF were found to be effective bases, while Na2CO3 performed poorly. Palladium sources were surveyed as well (3 mol % of palladium sources employed in Table S3 (Supporting Information)). The performances of Pd(OAc)2, Pd(COD)Cl2, and PdBr2 were found to be the best and mutually compatible. Interestingly, the zerovalent palladium species Pd2(dba)3 is less efficient. Various solvents were also screened for optimizing the yield (Table S4 (Supporting Information)). We found that DMF stood out as the best solvent even when the amount of Cs2CO3 was reduced from 5 to 3 mmol. In summary, the optimized conditions for the Heck reaction shown in Scheme 3 are loading 3 mol % of 2c, 3 mol % of Pd(COD)Cl2, and 3 mmol of Cs2CO3 into 1.0 mL of DMF. Next, various aryl bromides and heterocyclic bromides were employed as the substrates to examine and also extend the applicability of preligand 2c. The results are presented in Table 3. As shown in Table 3, aryl bromides with electron-donating

Table 1. EDA Results for 3 at the ADF/ZORA/B3LYPD3(BJ) Theory Levela

a

ΔEPauli

ΔEelst

ΔEoi

ΔEdisp

ΔEint

48.6

−105.2 72.3%

−33.1 22.8%

−7.1 4.9%

−96.8

Energies are given in kcal/mol.

fold larger than ΔEoi (22.8%), showing the greater electrostatic character of the Pd−Cl bond. Interestingly, there is 4.9% of stabilizing energy that contributed from ΔEdisp, which is easily overlooked but is important in complexes with crowded substituents. Palladium-Catalyzed Heck Reactions using 2a−d as Preligands. Coordinated by a supramolecular tetradentate ligand, 3 is a stable complex. Therefore, it could be better to use a preligand/palladium ratio of 1/1 for these SPO-based hemilabile P−N ligands in palladium-catalyzed reactions. Preligands 2a−d were employed for the Heck reactions. Generally, Heck reactions are conducted at a higher temperature than Suzuki−Miyaura reactions.44 Accordingly; the catalytic reactions were carried out in DMF and conducted at higher temperatures (Scheme 3). A 20 mL Schlenk tube was Scheme 3. Model Heck Reaction with 4-Bromoanisole and Styrene as Substrates for Optimizing the Reaction Conditions for Preligands 2a−d

Table 3. Model Heck Reactions Employing 2c as Preliganda

charged with 1.0 mmol of substituted bromobenzene, 1.2 mmol of styrene, 3.0 mmol of base, 3.0 mol % of palladium salt, and 3.0 mol % of 2a−d. The mixture was allowed to react for a designated time and temperature. Among the three plausible products shown in Scheme 3, the linear trans-1,2-disubstituted ethylene was the major product. Meanwhile, the cis-1,2disubstituted ethylene as well as the branched 1,1′-disubstituted ethylene were expected to be the minor products. Among the four SPO-based hemilabile preligands, good performance of 2c was obtained in the preliminary screenings (entry 3 in Table 2). No branched product was detected, while

preligand

conversn (%)b

1 2 3 4

2a 2b 2c 2d

29 52 97/92c 60/80c

bromideb

conversn (%)c

yield (%)d

1 2 3 4 5 6 7

Me OMe C(O)Me C(O)H H NH2 CN

97 (96/4) 98 (96/4) 85 (100/0) 65 (100/0)

94 95 82 60 98 75 0

a

Conditions: 1.0 mmol of bromide, 1.2 mmol of styrene, 3.0 mmol of Cs2CO3, 1 mL of DMF, 3.0 mol % of Pd(COD)Cl2, 3.0 mol % of 2c, Pd/2c = 1/1, 100 °C, 12 h. bSubstituent in the para position of aryl bromides. cDetermined by NMR. dIsolated yield.

groups are better than those with electron-withdrawing groups (entries 1 and 2 vs 3 and 4). Poor performance was obtained for the case having the substituent CN, partially due to the poisoning of the palladium catalyst through coordination of the Lewis base site. Ligand 2c Assisted Palladium-Catalyzed Three-Component Reaction. Palladium-catalyzed three-component condensations of olefins, aryl halide, and carbon monoxide to the formation of cyclized regioisomers, as shown in Scheme 4, were first reported by Fiaud et al.45 The conception and practice of a step-efficient multicomponent reaction (MCR) is

Table 2. Model Heck Reactions Employing 2a−d as Preligandsa entry

entry

a

Conditions: 1.0 mmol of 4-bromoanisole, 1.2 mmol of styrene, 5.0 mmol of Cs2CO3, 1.0 mL of DMF, 3.0 mol % of Pd(OAc)2, Pd/L = 1/ 1, 100 °C, 12 h. bConversion yields were determined by 1H NMR. c 5.0 mmol of K2CO3 as base.

Scheme 4. Palladium-Catalyzed MCR Reaction with Norbornene, 2-Iodophenol, and 1 atm of Carbon Monoxide As Substrates

the linear trans-1,2-disubstituted ethylene was the major product. Moderate performances were observed in the cases of 2b,d (entries 2 and 4). For the model Heck reaction, 2a was the poorest preligand (entry 1). Therefore, 2c was chosen as the preligand for further optimization of reaction conditions thereafter. The performance of preligand 2d was improved if 5 F

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Organometallics

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attractive, since three or more compounds can be combined in a one-pot or sequential manner, in which the moieties of each components are principally maintained.46 Interestingly, the ratio of products P1 and P2 depends on the Pd(OAc)2 to ligand ratio, the temperature, and the amount of Tl(OAc).47 It was found in Fiaud’s work that compound P1 is the sole product if 2 equiv of a monodentate ligand such as PPh3 was used (entry 5 in Table 4).45a However, mixtures of

Scheme 5. Proposed Mechanism of the Formation of P1 and P2

Table 4. Three-Component Reaction of Olefin with Aryl Halide and Carbon Monoxidea entry

preligand

T (°C)

time (h)

P1/P2

yield (%)

1 2 3 4 5 6 7 8 9

2c 2c 2c 2c PPh3 dppe dppp dppp dppp

100 100 100 60 80 80 100 80 60

20 10 5 43 20 20 20 20 20

100/0b 100/0b 100/0b 100/0b 100/0 33/67 90/10 25/75