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Article

Synthesis, Characterization, Solution Behavior and Theoretical Studies of Pd(II) Allyl Complexes with 2-Phenyl-3H-indoles as Ligands

by
Maria Tomé
1,
Arnald Grabulosa
1,
Mercè Rocamora
1,
Gabriel Aullón
1,2,
Mercè Font-Bardía
3,
Teresa Calvet
4 and
Concepción López
1,*
1
Secció de Química Inorgànica, Departament de Química Inorgànica i Orgànica, Universitat de Barcelona, Martí i Franquès 1–11, E-08028 Barcelona, Spain
2
Institut de Química Teòrica i Computacional, Universitat de Barcelona. Martí i Franquès 1–11, E-08028 Barcelona, Spain
3
Unitat de Difracció de Raigs-X, Centre Científics i Tecnològics (CCiT) Universitat de Barcelona, Solé i Sabaris 1–3, E-08028 Barcelona, Spain
4
Department de Cristal·lografia, Mineralogia i Dipòsits Minerals, Facultat de Geologia, Universitat de Barcelona, Martí i Franqués s/n, E-08028 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Catalysts 2019, 9(10), 811; https://doi.org/10.3390/catal9100811
Submission received: 9 September 2019 / Revised: 24 September 2019 / Accepted: 24 September 2019 / Published: 27 September 2019
(This article belongs to the Special Issue Ligand Design in Metal Chemistry: Reactivity and Catalysis)
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Abstract

:
The study of the reactivity of three 2-phenyl-3H-indole ligands of general formulae C8H3N-2-(C6H4-4-R1)-3-NOMe-5-R2 (1) [with R1 = H, R2 = OMe (a); R1 = R2 = H (b) or R1 = Cl, R2 = H (c)] with [Pd(η3-1-R3C3H4)(μ-Cl)]2 (R3 = H or Ph) has allowed us to isolate two sets of new Pd(II)-allyl complexes of general formulae [Pd(η3-1-R3C3H4)(1)Cl] {R3 = H (2) or Ph (3)}. Compounds 2a–2c and 3a–3c were characterized by elemental analyses, mass spectrometry and IR spectroscopy. The crystal structures of 2a, 3a and 3b were also determined by X-ray diffraction. 1H-NMR studies reveal the coexistence of two (for 2a–2c) or three (for 3a–3c) isomeric forms in CD2Cl2 solutions at 182 K. Additional studies on the catalytic activity of mixtures containing [Pd(η3-C3H5)(μ-Cl)]2 and the parent ligand (1a–1c) in the allylic alkylation of (E)-3-phenyl-2-propenyl (cinnamyl) acetate with sodium diethyl 2-methylmalonate as well as the stoichiometric reaction between compounds 3a and 3c with the nucleophile reveal that in both cases the formation of the linear trans- derivative is strongly preferred over the branched product. Computational studies at a DFT level on compound 3a allowed us to compare the relative stability of their isomeric forms present in solution and to explain the regioselectivity of the catalytic and stoichiometric processes.

Graphical Abstract

1. Introduction

Indole is one of the most important heterocycles for its presence in bioactive natural products, pharmaceuticals, and agrochemicals [1,2,3,4,5,6,7,8,9]. Indole derivatives are not only “privileged structures” in Medicinal Chemistry [1,2,3,4,6,10,11,12], due to their biological activity, but also valuable reagents for the design and synthesis of compounds with interesting properties and applications in a variety of fields [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]. The construction and functionalization of indoles have been studied since long ago; however, and as mentioned by Prof. M. Bandini some years ago “this field had a formidable boom across the new millennium when catalysis started revolutionizing the chemistry of indole” [7]. Interesting applications of novel indole derivatives as dyes [1,2,3,13], as components of Dye Sensitized Solar Cells (DSSC) [1,2,3,5] and as precursors in synthesis of organic compounds, including some natural products, have been reported [1,2,3,15,17].
Indoles derivatives are also attracting a great deal of interest in coordination and organometallic chemistry because the binding of a transition metal atom to the indole nitrogen may introduce significant variations on the chemical, physical, photo-optical properties and catalytic or biological activities of this type of heterocycles [18]. However, M(II) complexes with 2-substituted-3H-indoles as ligands are not common. Mono-, di-, and even polymeric Pd(II), Zn(II), Cd(II), Co(II), complexes derived from 2-diformylmethylene-3,3-dimethylindole have been reported by Prof. Kaledi’s group [19,20]. Some years ago, we focused our interest on 3-methoxyimino-2-phenyl-3H-indoles and the results obtained so far revealed not only that they may act as an N-donor group (Figure 1A) [21,22] or as a bidentate [C(sp2, phenyl),N]− ligand (Figure 1B,C) [21,22,23] but also, that the resulting complexes exhibit interesting properties and biological activities. For instance, compounds A and B are more potent cytotoxic agents than their parent free ligands and even than cisplatin in MCF-7 and MDA-MB231 breast cancer cell lines [21,23].
Despite the increasing interest on: (a) novel transition metal complexes with indole ligands and especially the 2-sustituted-3H-indoles [18,19,20], (b) the role of Pd(II) in heterocyclic chemistry and in C-C bond formation (stoichiometric or catalytic) [24,25,26,27] and, (c) the relevance of “Pd(II)-allyl compounds” in homogeneous catalysis and their exciting solution behavior [25,26,27,28,29,30,31,32,33,34,35], Pd(II) compounds containing simultaneously “2-phenylindole” units and η3-allyl ligands still remain unknown.
Here we present the first examples of Pd(II) complexes with 3-methoxyimino-2-phenyl-3H indoles (1a-1c) (shown in Scheme 1) and the allyl groups (η3-1-R3C3H4) (R3 = H or 1-Ph) as ligands together with a study of their solution behavior and their potential utility in the allylic alkylation of (E)-3-phenyl-2-propenyl (cinnamyl) acetate with sodium diethyl 2-methylmalonate. Computational studies, based on DFT calculations, were undertaken in order to rationalize the stability and relative abundance of the co-existing isomeric forms in solution.

2. Results and Discussion

2.1. Synthesis of the Pd(II) Compounds

Compounds [Pd(η3-1-R3C3H4){C8H3N-2-(C6H4-4-R1)-3NOMe-5-R2}Cl] [R3 = H (2a-2c) or R3 = Ph, (3a-3c)] were prepared by treatment of the corresponding [Pd(η3-1-R3C3H4)(μ-Cl)]2 (R3 = H or Ph) [36,37] complexes with the proper 2-phenyl-3H-indole ligand (1a-1c) {in a molar ratio Pd(II):1 = 1:1} in CH2Cl2 at 298 K (Scheme 1).
The new products (2a–2c and 3a–3c) are stable solids at 298 K, they exhibit high solubility in acetone, CHCl3 and CH2Cl2, but they are practically insoluble in n-hexane and diethylether. Characterization data are presented in the Supplementary Materials. Elemental analyses of 2a–2c and 3a–3c were consistent with the proposed formulae and their ESI+ mass spectra showed a peak due to the corresponding {[M]-Cl}+ cation.
In the IR spectra of the new Pd(II) complexes the position of the band due to the stretching of the exocyclic >C=N− group was practically identical to those of the parent free ligands and compounds A–C presented in Figure 1 [21,22,23] indicating that a) the Noxime atom was not bound to the Pd(II) atom and b) the oxime unit adopted the anti-(E) form. X-ray diffraction studies of compounds 2a, 3a and 3b (see below), confirmed these findings. Keeping this in mind, complexes 2a–2c may exhibit two different isomeric forms (Figure 2) that differ in the relative arrangement between the central Cβ-Hβ bond of the allyl ligand and the phenyl ring (highlighted in deep red in Figure 2) of the bicyclic system.
For compounds 3a–3c the situation is markedly different due to presence of the non-symmetric 1-PhC3H4 allyl group. Assuming that the oxymino group adopts the anti-(E) form, eight different isomers (Figure 3A–H) could be formed in principle. They may differ in the relative disposition of the central Cβ-Hβ bond in respect to the phenyl ring of the bicyclic unit [endo- (in A–D) or exo- (in E–H)]. Moreover, the substituted carbon of the allyl ring (Cα) could be located in a cis- (in A, B, E and F of Figure 3) or trans- (Figure 3, isomers C, D, G and H) arrangement in respect to the indole nitrogen and, finally the phenyl ring of the (η3-1-PhC3H4) ligand could be in a syn- (in A, C, E and G) or anti- (in B, D, F and H) position in respect to the central hydrogen (Hβ).

2.2. Description of the Crystal Structures of Compounds 2a, 3a and 3b

Compounds 2a, 3a and 3b were also characterized by X-ray diffraction. Crystal data and details of the refinement are presented in Table 1.
The crystal structure of 2a consists of molecules of [Pd(η3-C3H5){C8H3N-2-(C6H5)-3-NOMe-5-(OMe)}Cl] (Figure 4) in which the Pd(II) atom [Pd(1)] is in a slightly distorted square-planar environment and it is bound to the heterocyclic nitrogen of the indole [N(1)], thus confirming the results obtained by IR studies. A chlorido ligand [Cl(1)] and the C3H5 moiety (in a η3-fashion) fullfil the coordination sphere of the Pd(II). The differences detected in the Pd1-C17 [2.189(6)Å] and Pd-C19 [2.072(6)Å] bond lengths can be ascribed to the influence of the ligand in a trans- arrangement (Cl1 and N1, respectively). The Pd-N/C/Cl bond lengths are similar to those reported for related [Pd(η3-C3H5)(N-heterocyclic ligand)Cl] complexes [35,36,37,38,39,40,41].
The indole unit is planar and nearly orthogonal to the coordination plane of the Pd(II) and the phenyl ring on position 2 forms an angle of ca. 35.0° with the fused heterocycle. This arrangement of rings allows intramolecular hydrogen contacts between the heteroatoms of the “=NOMe” unit and the hydrogen atoms H10 and H5 [distances N2···H10 = 2.578Å and O2···H5 = 2.521Å]. These short contacts, which reduce the flexibility of the pendant arm, were also observed in the crystal structures of the cyclometallated compounds containing Pd(II) or Ru(II) as well as in the trans- and cis- isomers of the Pt(II) complexes (A–C) shown in Figure 2 and appear to be characteristic of this family of ligands [21,22,23].
The central carbon atom of the allyl group C18 [Figure S1, (a)] is located out of the coordination plane of the palladium and on the same side as the C1 atom of the indole unit (endo-), therefore crystals of 2a contain the endo- isomer (Figure 2, type A). The plane defined by three carbon atoms of the allyl group forms angles of 51.16° and 38.79° with those of the bicyclic system indole and the phenyl ring (C9–C14) attached to it, respectively.
In the crystal the molecules are connected by C-H···O interactions involving the C17-H17B atoms of the allyl group of a molecule sited at (x,y,z) and the oxygen O2 of a proximal unit at (1-x,1-y,z) [distance O2···H17B = 2.596Å] (Figure S2). Thus, this indicates that the OMe substituent on the indole unit plays a crucial role in the molecular assembly in the solid state.
The X-ray crystal structure of 3a confirms the presence of [Pd(η3-1-PhC3H4){C8H3N-2-(C6H5)-3-NOMe-5-(OMe)}Cl] molecules (Figure 5), in which the indole ligand binds to the Pd(II) through the heterocyclic nitrogen, N1. The orientation of the heterocycle as well as bond lengths and bond angles are similar to those of 2a. The phenyl ring forms angles of 45.50° and 43.85° with the indole and the oxymino group, respectively, thus allowing weak intramolecular C14-H14···N2 and C5-H5···O2 contacts [distances N2···H14 and O2···H5 being 2.610Å and 2.502Å, respectively). The Cl1 ligand and the (η3-1-PhC3H4) allyl occupy the remaining coordination sites of the Pd(II).
In contrast with the results obtained for its analogue 2a, the central C18 atom of the allyl ring of 3a and the atom C1 of the indole are located in opposite sides of the coordination plane of the Pd(II) atom (exo-). Besides this, the substituted carbon atom of the allyl ring (C19) is in a cis- arrangement in relation to the Pd1-N1 bond and the phenyl ring of the 1-PhC3H4 ligand occupies the syn- position [Figure S1, (b)]. All these findings confirm that the molecules present in the crystals of 3a correspond to the exo-, cis-N, syn- isomer (E in Figure 2). This distribution of rings and substituents allows intramolecular C-H···π interactions between: (a) the H14 atom and the phenyl ring of the allyl group, and (b) the H21 atom of the pentagonal cycle of the 3H-indole [distances H14···centroid of the (C20-C25) ring = 3.477Å and between H21 and the centroid of the ring defined by N1, C1, C6, C7 and C8) = 3.218Å].
The assembly of the molecules in the crystals of 3a is markedly different from that of 2a. In 3a two proximal molecules at (x,y,z) and (1−x,1−y,−z) are connected by two C18-H18···Cl1 short contacts (distance: 2.982 Å) forming dimers (Figure S3) that are assembled by C-H···π interactions.
Despite the formal similarity between compounds 3a and 3b, the crystal structure of 3b is more complex than that of 3a due to the presence of two independent molecules of [Pd(η3-1PhC3H4){C8H3N-2-(C6H5)-3-NOMe)}Cl] (hereinafter referred to as I and II) that are shown in Figure 6. In both molecules the Pd(II) atoms are bound to a chlorido {Cl1A or Cl1B}, the substituted allylic ligand in a η3- fashion and the nitrogen of the indole ligand (N1A and N1B in I and II, respectively).
Bond lengths and angles around the Pd(II) atoms are similar to those found for compound 3a and related complexes containing [Pd(η3-1-PhC3H4)(N-donor ligand)Cl] [32,38,39,40,41]. In molecules I and II the phenyl ring of the indole unit and the central C-H bond of the allyl ligand are located on opposite sides of the coordination plane of the Pd(II) atoms (exo-). Moreover, the substituted carbon of the allyl ligand (C18A in I and C18B in II) and the indole nitrogen are in a cis- arrangement [bond angles N1A- Pd1- C18A = 94.75(1)° and N1B-Pd1B- C18B = 95.52(12)°] and, finally the phenyl ring is in the syn- position in relation to the central hydrogen atom (H17A in I and H17B in II)] of the allyl ring (syn-) [Figure S1]. All these findings indicate that both molecules correspond to the exo-, cis-N, syn- isomer, exactly the same type of isomer (E in Figure 3), as that found in the crystals of 3a.
Bond lengths and angles of molecules I and II are similar, and the most evident difference lies in the coplanarity between the oxymino group and the indole unit, which is higher in molecule II than in molecule I. The orientation of the phenyl defined by the set of atoms (C10A-C14A in I or C10B-C14B in II) versus the bicyclic system is a bit different (ca. 2.6°). Despite of these differences, again the relative arrangement of the NOMe unit allows short intramolecular contacts (Figure S1c) similar to those found in 2a, 3a and also in other Pt, Ru, or Pd complexes prepared previously in our group [21,22,23].
In the crystals, (Figure S4) two molecules of the same kind are assembled by CH···Cl intermolecular short contacts. Further, C-H···π interactions involving the H11A of a type I molecule with the C19A-C24A ring of a close unit, and the allylic hydrogen H18A and the phenyl ring on site-2 of a proximal type II unit, generate the molecular architecture.

2.3. Solution Studies

2.3.1. Allylic Alkylation Reactions

As mentioned above, the increasing interest on indole-chemistry and also on Pd(II)-allyl complexes is mainly due to their potential utility in synthesis and catalysis [1,2,3,4,5,25,26,27,28,34,35,42,43,44]. However, as far as we know, the use of 2-phenyl-3H-indoles or their transition metal complexes in homogeneous catalysis still remains unexplored. Since: (a) palladium(II) catalytic allylic alkylation is one of the most widely studied processes due to the formation of C-C and C-heteroatom bonds that is relevant in synthesis, including the preparation of natural products [25,26,27,28,44] and, (b) there is a lack of studies on the use of indoles in Pd(II) catalyzed allylic alkylations, we also investigated the potential utility of compounds 1a-1c in the allylic alkylation of (E)-3-phenyl-2-propenyl (cinnamyl) acetate with sodium diethyl 2-methylmalonate (Scheme 2).
In all the studied reactions the precursors were prepared in situ by treatment of [Pd(η3-C3H5)(μ-Cl)]2 and the corresponding ligand (1a–1c) and the catalytic processes were performed in THF under mild experimental conditions using different reaction periods (t). Results, presented in Table 2, reveal that the indole ligands 1a–1c are active in the catalytic alkylation of cinnamyl acetate. For t = 24 h the process gave: the linear trans-(E) product (4), the branched derivative (5) and 1-cinnamyl-3-ethyl-2-methylmalonate (6). Under these experimental conditions the conversion varies from 87% (for 1b) to 91% (for 1c), but the presence of compound 6 reduces the effectiveness of the catalytic systems 1a, 1b or 1c and [Pd(η3-C3H5)(μ-Cl)]2. It should be noted that compound 6 is also formed when cinnamyl acetate is treated with the nucleophile in THF under identical experimental conditions, but in the absence of the catalyst [32,33].
Better results were obtained for longer reaction periods [t = 96 h, (Table 2, entries IV-VI)]. Conversions increased and the relative abundance of the undesirable side product (6) decreased considerably. It should be noted that for 1c no evidence of the presence of 6 was detected. In these cases, the formation of the linear trans-(E) product (4) was strongly preferred over that of the branched isomer (5). The comparison of results obtained after 96 h, also reveal that the regioselectivity of this process towards the linear product increases according to the sequence: 1a < 1b ≤ 1c.
Scheme 3 shows two important steps [i) and ii)] of the mechanism accepted for palladium catalyzed allylic alkylation of cinnamyl acetate with soft nucleophiles (such as sodium diethyl 2-methylmalonate) [42,43,44] where L1 and L2 represent either two monodentate ligands (commonly a N- donor and a chlorido) or one bidentate ligand. It is well-known that the regio-, as well as the stereoselectivity, of the process are dependent on several factors that include the number and structures of the different isomeric forms of the intermediate species (IS) formed in step ii), their interconversion rates and the ease with which they undergo the nucleophilic attack in solution. [18,23,42,43,44].
In compounds 3a–3c the environment of the Pd(II) atom is similar to that of the intermediate species IS with the ancillary ligands being a Cl− and the corresponding indole (1a–1c). In view of this and the results obtained from the catalytic studies we also investigated the direct reaction between the allyl compounds 3a and 3c separately with an excess of sodium diethyl 2-methylmalonate in THF at 298 K (stoichiometric reaction). These reactions were instantaneous and gave, after work-up, a mixture of the trans-(E) isomer of the linear product (4) and the branched derivative (5) in molar ratios of 98.3:1.7 (for 3a) and 99.6:0.4 (for 3c). It should be noted that the presence of the side product cis-(Z) isomer of the linear product and compound 6 were not detected by NMR. Therefore, the preferential formation of the linear trans-(E) product in the catalytic and stoichiometric reactions can be explained assuming that the attack of the nucleophile takes place at the terminal Cγ atom of the (η3-1-PhC3H4) ligand of one or more isomers of IS.
In order to get further information about the number of isomeric forms of 3a-3c present in solution and their characteristics, we also studied their solution behavior by NMR. For comparison purposes a parallel study with their analogues 2a–2c with the (η3-C3H5) ligand was also included.

2.3.2. Study of the Solution Behaviour of the New Pd(II) Allyl Compounds

1H-NMR spectra of 2a–2c in CD2Cl2 at 298 K showed broad signals (Figures S5–S7). This could be indicative of the co-existence of several isomeric species in solution. Since: a) the X-ray crystal structures of compounds 2a, 3a and 3b confirmed that the Pd(II) atom was bound to the heterocyclic nitrogen of the indole ligand, we assumed that in all the isomers of compounds 2 the indole ligands behaved as Nindole donor group and the anti-(E) form adopted by the oxymino moiety was retained. VT-NMR studies in CD2Cl2 for 2a–2c, (Figures S5–S7) showed that upon cooling the signals detected in the 1H-NMR spectra became narrower and at 182 K two sets of superimposed groups of resonances of relative intensities 1.00:0.60 (for 2a); 1.00: 0.62 (for 2b) and 1.00:0.65 (for 2c)] were clearly identified (Figures S8–S10). These findings suggest the co-existence of the two isomeric forms of compounds 2 [A (endo-) and B (exo-) depicted in Figure 2] and that the energy required for their interconversion is small.
The 1H-NMR spectra of CD2Cl2 solutions of compounds 3a–3c at 298 K exhibited broad signals (for illustrative purposes that of 3a is shown in Figure S11), but upon cooling the resolution of the spectra improved considerably and at 182 K (Figures S11,S12) two sets of superimposed signals of relative intensities 1.00:0.64 were clearly identified, thus suggesting the presence of two isomeric species {herein after referred to as 3aI (major) and 3aII (minor)} in solution. However, a careful analysis of the signals observed indicated the presence of other minor species in low abundance (<10%). The 1H-NMR spectra of compounds 3b and 3c at 182 K, also revealed the presence of two major isomers in solution in molar ratios 1.00:0.74 and 1.00:0.62 for 3b and 3c, respectively. (Figures S13 and S14). It should be noted that additional set of signals with lower intensities suggested the presence of traces of another isomer of 3b; while for 3c, no evidences of the coexistence of other species in solution were detected by NMR at 182 K.
For the two major isomers, detected in the CD2Cl2 solutions of 3a–3c at 182 K, the values of the coupling constants 3J(Hγ, Hβ) indicate that the phenyl ring is in the syn- position in relation to the Hβ hydrogen, and the chemical shifts of the allylic Hantiα Hsynα and Hγ nuclei were similar to those found in related complexes holding the “[Pd(η3-1-PhC3H4)Cl]” and a neutral organic ligand bound to the Pd(II) through a Nsp2 atom in a cis- arrangement to the substituted carbon of the allyl ligand [32,33] and the analysis of NOE peaks in the [1H-1H] NOESY spectrum (Figure S12) confirmed this hypothesis. On these bases, we assumed that the major isomers of 3a–3c present in CD2Cl2 solution at 182 K differ exclusively in the orientation of the allyl unit (endo- or exo-). The low abundance of the remaining minor species detected by NMR did not allow us to identify them unambiguously. Computational studies (described in the following section) allowed us to clarify this point.

2.4. Computational Studies

In a first attempt to rationalize the experimental results and in particular: (a) to explain the coexistence of several isomers of compounds 3a–3c and their relative stability in solution under the experimental conditions, (b) to rationalize the preferential formation of the linear trans-(E) product in the Pd catalyzed allylic alkylation of cinnamyl acetate with sodium diethyl 2-methylmalonate versus the branched derivative and, (c) to try to clarify the origin of the formation of the branched product (5), we decided to undertake DFT calculations.
Since NMR studies revealed that compounds 3a–3c showed a similar solution behavior in CD2Cl2, the computational studies were carried out for 3a as a representative product of this series. Computational studies were performed assuming that in all the cases the oxymino unit retained the anti- (E) form. Experimental IR and NMR data as well the X-ray diffraction studies presented in this work support this hypothesis. Therefore, only eigth isomers of compound 3a (A-H, in Figure 3 with R1 = H and R2 = OMe) were selected for this study.
Computational calculations carried out using the B3LYP hybrid functional [45,46] and the LANL2DZ basis set [47] implemented in the Gaussian09 program. [48] In the first step, geometries of the eight isomers were optimized (Figure S15) and final atomic coordinates are presented in Tables S1–S8. Afterwards the total energy (ET) of the eight isomers was calculated in the gas phase and in CH2Cl2 solution. As shown in Table S9, in the gas phase minima (ET) values correspond to two isomers. One of them E (exo-, cis-N, syn-) is that found the crystal structure of 3a; while the other was isomer A (endo-, cis-N, syn-). This suggests that that these isomers, that differ exclusively in the conformation of the allyl ligand, are clearly more stable than the remaining six.
Since VT-NMR studies described above were carried out in CD2Cl2, we also determined the ET values in dichloromethane by PCM calculations, [49] (Table S9). The obtained ET values and the calculated relative energies [ΔET = ET (for a given isomer) − ET (for isomer E, that has the lowest ET)] increase according to the following sequence: E (exo-, cis-N, syn-) ≈ A (endo-, cis-N, syn-), ΔET = 0.01 < G (exo-, trans-N, syn-), ΔET = 1.22 < C (endo-, trans-N, syn-), ΔET = 1.82 < < H (exo-, trans-N, anti-), ΔET = 3.47 ≤ D (endo-, trans-N, anti-), ΔET = 3.58 < F(exo-, cis-N, anti-), ΔET = 3.67 << B(endo-, cis-N, anti-), ΔET = 4.36.
Now the energies of isomers A (endo-, cis-N, syn-) and E (exo-, cis-N, syn-) only differ in 0.01 kcal/mol and they may be considered as isoenergetics. On these basis, the energy required to change orientation of the central Cβ-Hβ bond of the allyl ligand in relation to the indole from exo- in E to endo- in A is expected to be small enough as to allow the co-existence of both isomers at room temperature we will return to this point later on. Isomers C (endo-, trans-N, syn-) and G (exo-, trans-N, syn-), that can visualized as derived from their analogues A and E by a cis-N → trans-N isomerization process, are higher in energy than A and E but the differences are small (1.21 and 1.82 kcal/mol, for C–A and G–E, respectively).
It is interesting to point out that in isomers H (exo-, trans-N, anti-), D (endo-, trans-N, anti-), F (exo, cis-N, anti-) and B (exo-, cis-N, anti-) the phenyl ring of the 1-PhC3H4 ligand is on an anti- position in relation to the Cβ-Hβ bond. The (endo-, cis-N, anti-) isomer (B) has the highest ET of the set, this can be due to steric effects arising from the proximity of two bulky groups: the phenyl ring attached to the allyl unit and the bicyclic system of the N-donor ligand.
We also calculated the Boltzmann’s distribution using the calculated energies at 182 K and 298 K. Results reveal that at 182 K only isomers A, E and to a minor extent also isomer C (endo-, trans-N, syn) had relevant contributions (49, 49 and 2%, respectively). NMR studies at 182 K indicated: (a) the coexistence of two isomers (in molar ratios ranging from 1.0:0.6 to 1.00:0.8) and small amounts of other minor species; (b) that in the major components the arrangement of the Cα carbon of the allyl and the nitrogen occupied adjacent positions (cis-N), the phenyl ring of the allyl unit was in the syn- site and differed in the conformation (exo- or endo-) of the 1-PhC3H5 ligand that is to say corresponding to isomers A and E. That is consistent with the results obtained from the computational studies. On this basis we assume that the minor specie present in CH2Cl2 solutions at 182 K is isomer C (endo-, trans-N, syn-).
When Boltzmann’s population analyses was carried out at 298 K (Table S9): contributions of the major isomers A (endo-, cis-N, syn-) and E (exo-, cis-N, syn-) decreased (from 49% to 46%) that of C (endo-, trans-N, syn-) increased (from 2% to 6%) and isomer G (exo-, trans-N, syn-), with no participation in the isomeric distribution at 182 K had also a tiny contribution. It is interesting to point out that changes on location of the nitrogen atom in relation to the Cα carbon of the allyl ligand (cis- in A and E and trans- in C and G) may introduce significant changes in the distribution of charge. In order to get further information on this problem, molecular orbital (MO) calculations for the optimized geometries of isomers A–H were analyzed. In all cases, (Table S10) the HOMO-1 and HOMO orbitals are centered on the Cl− ligand with a tiny contribution of the Pd(II) atom; while the LUMO is mainly a MO of the 2-phenyl substituted 3-H indole ligand. In contrast, the LUMO+1, has a relevant contribution of the 1-PhC3H4 ligand. This molecular orbital would be involved in the nucleophilic attack, that is expected to occur in the more electrophilic site. In view of this and in order to fulfill this study we also undertook a comparative analysis of the charge distribution on the Cα-Cγ carbon atoms of the allyl ligand for the eight isomers. As shown in Table S11, for the major isomers (A and E) the orientation of the allyl group does not introduce significant variations in the charge distribution of the Cα-Cγ carbon atoms and the values are very similar to those obtained for the pair of isomers C and G, and therefore this approach did not bring any valuable information on the proclivity of the terminal or substituted carbon atoms (Cα and Cγ) to undergo the nucleophilic attack and therefore to explain the preferential formation of the lineal product (4) versus the branched derivative (5).
More interesting were the results obtained from the analyses of the fragment charges obtained from Natural Population analysis. As shown in Table S12, for the two major isomers (A and E with an abundance of ca. 46% each determined according to Boltzmann’s distribution at 298 K), the charge of the terminal CH2 unit is positive and very similar for both isomers, while that of the CH unit is clearly negative. In view of this, the nucleophilic attack is expected to occur on the CH2 unit, leading to the linear product. In isomers C and G with a trans-Cγ,N arrangement, opposite orientation of the allyl ligand and calculated abundancies of 6% and 2%, respectively at 298 K), the differences on the charges of these two fragments are not as spectacular as for the pair (A, E). However, for the couple (C and D) the charge of the CH2 fragment is smaller than for their partners (A and E) and that of the CHPh unit follows the opposite trend. In fact, the values obtained for isomer G suggest that the CHPh unit may be more prone to undergo the nucleophilic attack than the CH2. This would explain the formation of the branched derivative in both the stoichiometric and catalytic reactions. Compounds 3b and 3c are very similar to 3a except for the nature of the substituents on the indole unit, they exhibit a similar behavior in solution and therefore we assume that the conclusions reached for 3a could also be extended to compounds 3b and 3c.

3. Experimental Section

3.1. Materials and Methods

Ligands 1a–1c and the allylic compounds [Pd(η3−1-R3C3H4)(μ-Cl)]2 (R3 = H or Ph) were prepared as described previously [21,22,23,24,36,37]. Sodium diethyl 2-methylmalonate (0.5 M in THF) was prepared from diethyl-2-methyl malonate and NaH in THF at 273 K. The remaining reagents were obtained from Aldrich and used as received. The solvents were distilled and dried before use [50]. For the preparation of the complexes the reaction flasks were protected from the light with aluminum foil.
Elemental analyses (C, H, N) were performed in an EA-1108 CE Instruments (Thermo Fisher, Whaltham, MA, USA) apparatus at the Servei d’Anàlisi Elemental dels Centres Científics I Tecnològics (Univ. de Barcelona). Organometallic compounds were analyzed using WO3 or SeO as combustion catalysts. ESI+ mass spectra were performed at the Servei d’Espectrometria de Masses (Univ. Barcelona) with a VG-Quattro Fisions instrument (Micromass Ltd., Wythenshawe, UK). IR spectra were obtained with a Nicolet 400-FTIR instrument (Thermo Fisher, Whaltham, MA, USA) using KBr pellets. Routine 1H NMR spectra were obtained with a Mercury-400 instrument (Bruker Gmb, Mannheim, Germany). NMR spectra were recorded with a Varian VRX-500 (Palo Alto, CA, USA) or a Bruker Advance-DMX 500 instrument (Bruker Gmb, Mannheim, Germany) at 298 K. The latter equipment was also used to perform the VT-NMR studies and to register the [1H-1H]-NOESY spectra at 182 K. Characterization data for the new compounds are included as Supporting Information.

3.2. Preparation of the Compounds

3.2.1. General Procedure for the Synthesis of Compounds [Pd(η3-C3H5){C8H3N-2-(C6H4-4-R1)-3-NOMe-5-R2}Cl] [with R1 = H, R2 = OMe (2a); R1 = R2 = H (2b) or R1 = Cl, R2 = H (2c)]

[Pd(η3-C3H5)(μ-Cl)]2 (100 mg, 2.73 × 10−4 mol) was treated with CH2Cl2 (ca. 5 mL). Then this solution was added to another one solution by 5.47 × 10−4 mol of the corresponding ligand (148, 129 or 149 mg for 1a–1c, respectively) in the minimum amount of CH2Cl2. The resulting reaction mixture was stirred at 298 K during 1h. After this period the undissolved materials were filtered, and the filtrate was concentrated to dryness on a rotary evaporator. The isolated residue was afterwards dissolved in CH2Cl2 (3 mL). Addition of n-hexane (≈ 3 mL) followed by slow evaporation of the solvents at 298 K produced crystals of 2a and microcrystalline solids for 2b and 2c, that later on were collected, air-dried and afterwards dried in vacuum for 2 days. Yield: 209 mg (85%), 204 mg (89%) and 212 mg (85%) for 2a, 2b and 2c, respectively.

3.2.2. General Procedure for the Synthesis of Compounds [Pd(η3-1-PhC3H4){C8H3N-2-(C6H4-4-R1)-3-NOMe-5-R2}Cl] [with R1 = H, R2 = OMe (3a); R1 = R2 = H (3b) or R1 = Cl, R2 = H (3c)]

A 1.74 × 10−4 mol amount of the corresponding ligand {1a (46 mg), 1b (41 mg) or 1c (47 mg) was treated with 5 mL of CH2Cl2 and stirred at room temperature until complete dissolution. Then, this solution was added to another one formed by 45 mg (8.69 × 10−5 mol) of [Pd(η3-1-PhC3H4)(μ-Cl)]2 in the minimum amount of CH2Cl2 (ca. 5 mL) and the resulting reaction mixture was stirred at 298 K for 1 h. After this period, it was filtered, and the red filtrate was concentrated to dryness on a rotatory evaporator. After cooling to room temperature, the gummy residue was treated with CH2Cl2 (2 mL). Addition of diethyl ether (ca. 2 mL) followed by evaporation of the solvents at 278 K produced crystals of 3a and 3b suitable for X-ray and a microcrystalline solid for 3c. Yields: 87 mg (91%), 77 mg (89%) or 84 mg (91%) for 3a–3c, respectively.

3.3. Crystallography

A prism-like specimens of 2a, 3a or 3b (sizes in Table 1) were used for the X-ray crystallographic analysis. The X-ray intensity data were measured on a MAR 355 system equipped with a graphite monochromator and a Mo- fine focus sealed tube (λ = 0.71073 Å).
The frames were integrated with the MAR345 software package using a “MARSCALE” algorithm. The integration of data using a monoclinic (for 2a and 3a) or a triclinic (for 3b) unit cell yielded: for 2a a total of 3861 reflections to a maximum θ angle of 32.34° (0.66 Å resolution), of which 3861 were independent (average redundancy 1.000, completeness = 58.7%, Rint. = 5.43%, Rsig = 3.98%) and 3146 (81.48%) were greater than 2σ(F2); for 3a a total of 19380 reflections to a maximum θ angle of 30.88° (0.69 Å resolution), of which 5572 were independent (average redundancy 3.478, completeness = 78.8%, Rint. = 2.5%, Rsig = 1.71%) and 5338 (95.80%) were greater than 2σ(F2) and, for 3b a total of 18112 reflections to a maximum θ angle of 30.36° (0.70 Å resolution), of which 9882 were independent (average redundancy = 1.833, completeness = 75.8%, Rint. = 2.07%, Rsig = 2.00%) and 9033 (91.41%) were greater than 2σ(F2). The final cell constants (presented in Table 1) are based on the refinement of XYZ centroids of reflections above 20σ(I). The calculated minimum and maximum transmission coefficients (based on crystal size) are: 0.8700 and 0.8900 for 2a, 0.8900 and 0.9100 (for 3a) and 0.5000 and 0.500 (for 3b).
The structures were solved and refined with the SHELXTL computer program [51]. Final R factors and further details concerning the refinement of the structures of 2a, 3a and 3b are summarized in Table 1.
CCDC-1492860-1492862 contain the supplementary crystallographic data for 2a, 3a and 3b, respectively. These data can be obtained free of charge via hhtp://www.ccdc.cam.ac.uk/ const/retrieving.htlm or from the Cambridge Crystallographic Data Centre 12 Union Road, Cambridge CB2 1EZ, UK; fax (+44) 1223-336-033 or e-mail: deposit@ccdc.cam.ac.uk

3.4. Typical Procedure for Allylic Alkylation

The catalytic reactions were performed at 298 K in THF (5 mL) using 2.5 × 10−3 mmol of [Pd(η3-C3H5)(μ-Cl)]2, 5.0 × 10−3 mmol of the corresponding ligand 1a–1c, 0.5 mmol of cinnamyl acetate and 1.0 mmol of sodium diethyl 2-methylmalonate. The reaction was monitored by taking samples from the reaction. Each aliquot was diluted in Et2O, washed with H2O, dried over MgSO4 and then analyzed by GC using decane (0.258 mmol) as internal standard.
The product distribution of the alkylation experiments was measured on an Interscience Mega2 or Trace-DQS apparatus. The Interscience Mega2 was equipped with a DB1 column, length 30 m, inner diameter 0.32 mm, a film thickness of 3.0 μm, and a flame ionization detector. The Trace-DQS instrument had a HP-5 column (25 m in length, 0.5 μm film thickness, and 0.2 mm inner diameter) and was equipped with an electron impact mass detector.
These studies were performed under nitrogen. The stoichiometric alkylation reaction of 3a and 3c were performed at 298 K by adding an excess of sodium diethyl-2-methylmalonate (0.8 mL of a 0.5 M solution in THF) to a solution containing 3a (57 mg, 1.10 × 10−4 mol) or 3c (58 mg, 1.08 × 10−4 mol). The reaction was instantaneous, and H2O was added after 10 min. The reaction mixture was filtered over Celite. The filtrate was then treated with Et2O (∼15 mL), and the organic layer was washed with H2O (3 × 3 mL portions). The organic phase was dried over MgSO4, and the filtrate was concentrated to dryness on a rotary evaporator. The residue was dissolved in a minimum amount of Et2O and passed through a short SiO2 column (4.0 cm × 0.6 cm). The band released was collected and concentrated to dryness. The oily residue isolated contained, according to 1H NMR (500 MHz) and GC compounds 4 and 5 in molar ratios 98.3:1.7 for 3a and 99.4:0.6 for 3c.

3.5. Computational Studies

DFT calculations of compound [Pd(η3-1-PhC3H4){C8H3N-2-(C6H4-4-R1)-3-NOMe-5-R2}Cl} [with R1 = H, R2 = OMe and R3 = Ph (3a)], were carried out using the Gaussian09 package [48] and the B3LYP functional [45,46]. Effective core potentials (ECP) were used to represent the innermost electrons of the palladium atom and the basis set of valence double-ζ quality for associated with the pseudopotentials known as LANL2DZ [47]. The basis set for the main group elements (Cl, P, C, N, O and H) was 6–31G* [52,53]. Solvent effects of dichloromethane were taken into account by PCM calculations [49], keeping the geometry optimized for gas phase (single-point calculations).

4. Conclusions

Two new families of Pd(II)-allyl complexes containing simultaneously the 2-phenyl-3H-indoles C8H3N-2-(C6H4-4-R1)-3-NOMe-5-R2 (1) [R1 = H, R2 = OMe (a) or H (b) or R1 = Cl, R2 = H (c)] and the allyl ligands (η3-1-R3C3H4) with R3 = H (2a–2c) or Ph (3a–3c) have been prepared and characterized in the solid state and also in solution. In the new compounds ligands 1a–1c bind to the Pd(II) through the indole ligand and the X-ray diffraction studies of 2a, 3a and 3b, confirmed this finding and allowed the identification of the isomer present in the crystals [endo- in 2a or (exo-, cis-N, syn-) in 3a and also in the two different molecules (I and II) found in the crystals of 3b. VT 1H-NMR studies of CD2Cl2 solutions of the compounds in the range 298–182 K, provided conclusive evidence of the coexistence of several isomers in solution. At 182 K 1H-NMR spectra of 2a–2c suggested the presence of two isomers that differ in the relative arrangement of the central CH bond of the allyl and the phenyl ring of the indole scafold (endo- or exo-). The solution behavior of compounds 3a–3c is more complex and even at 182 K their 1H-NMR spectra showed several superimposed signals indicating the presence of two major components in solution and also small amounts (<10%) or even traces of other isomers.
Additional studies carried out at 298 K on: a) the catalytic activity of mixtures containing [Pd(η3-C3H5)(μ-Cl)]2 and the parent ligand (1a–1c) in the allylic alkylation of (E)-3-phenyl-2-propenyl (cinnamyl) acetate with sodium diethyl 2-methylmalonate, and b) the stoichiometric reaction between 3a or 3c and the nucleophile give the linear trans- derivative (4) preferentially over the branched product (5). The computational studies carried out with compound 3a as a representative model of the series, have allowed us to determine the relative stabilities of all its isomers in CD2Cl2 and their relative abundances at 298 K and 182 K. The results obtained agree with those obtained from the VT-NMR studies. Moreover, the comparison of the charges on the main fragments of the allyl group of 3a, shows that in the major isomers {endo- (or exo-), cis-N, syn-, A and E in Figure 3)} present at 182 K and also at 298 K, the charge on the CH2 unit is higher than that of the CHPh at the other end, and therefore more susceptible to undergo the attack by the nucleophile to produce the linear trans- compound (4). The catalytic studies and the stoichiometric reactions were performed at 298 K, according to Boltzmann’s distribution at this temperature isomers {endo- (or exo-), trans-N, syn-}, C and G, in Figure 3, that arise from A and E respectively by a cis-N → trans-N isomerization process, are also present in solution. In C and G isomers, the charges of the CH2 and CHPh units decrease and increase, respectively in relation to those of the major components (A and E). This finding could explain the attack of the nucleophile to the “CHPh” unit of the allyl unit to give the branched derivative (5).
To sum up, the studies in this work show the utility of 2-substituted–3H-indole ligands and their Pd(II) allyl complexes in the allylic alkylation of (E)-3-phenyl-2-propenyl (cinnamyl) acetate with sodium diethyl 2-methylmalonate. The results presented here constitute the first step of a new research area focused on other C-X bond formation processes (i.e. allylic aminations). Moreover, and according to the computational studies, the relative arrangement of the Nindole atom and the CHPh unit of the allyl group (cis- or trans-), produces significant variations in the electrophilicity of these arrays. On these basis, the replacement of the hydrogen atoms on positions 3 (or 4) of the bicyclic system by bulkier substituents may introduce significant steric hindrance as to modify the relative arrangement of the α-carbon of the 1-PhC3H4 ligand and the donor nitrogen, the charges on the terminal carbon atoms, and therefore to tune the regioselectivity of the processes towards the branched derivative. Further work in this area is on the way.

Supplementary Materials

An additional file (available at https://www.mdpi.com/2073-4344/9/10/811/s1) containing: 1. Characterization data for the new compounds: elemental analyses, mass spectrometry data, selected bands observed in the IR spectra and 1H and 13C{1H}-NMR data for compounds: [Pd(η3-C3H5){C8H3N-2-(C6H4-4-R1)-3-NOMe-5-R2}Cl] [with R1 = H, R2 = OMe (2a); R1 = R2 = H (2b) or R1 = Cl, R2 = H (2c)] and [Pd(η3-1-PhC3H4){C8H3N-2-(C6H4-4-R1)-3-NOMe-5-R2}Cl] [with R1 = H, R2 = OMe (3a); R1 = R2 = H (3b) or R1 = Cl, R2 = H (3c)] together with the chemical formulae of the major isomers present in solution. 2. Supplementary Figures (Figures S1–S15): Figure S1. Simplified views of structures of the molecules found in the crystals of compounds 2a, 3a and 3b [(a) –(c), respectively]. Figure S2. Simplified view of the assembly of molecules of 2a in the crystals by two co-operative C-H···O short contacts (red dotted lines) involving the C17-H17B bond of a molecule and the O1 atom of another unit and viceversa. Figure S3. Schematic view of the intramolecular C-H···O2, C-H···N2 short contacts and the “cooperative” assembly of two molecules of 3a by intermolecular C18-H18···Cl1 interactions, forming dimers. Figure S4. Schematic view of the intramolecular C-H···O short contacts in molecules I and II of compound 3b, and the intermolecular CH···Cl short contacts and C-H···π interactions. Figure S5. 1H-NMR spectra (500 MHz) of compound [Pd(η3-C3H5){C8H3N-2-(C6H4-4-R1)-3-NOMe-5-R2}Cl] (with R1 = H, R2 = OMe), 2a in CD2Cl2 at T = 298 K and 273 K. Figure S6. 1H-NMR spectra of compound 2b in CD2Cl2 at T= 298 K and 273 K. Figure S7. 1H-NMR spectra of 2c in CD2Cl2 at T = 298 K and 273 K. Figure S8. Partial views of the 1H-NMR spectrum of 2a in CD2Cl2 at 182 K, showing the presence of two sets of superimposed signals suggesting the presence of two isomers [2aI and 2aII (major and minor components, respectively)]. The resonances due to the allylic protons of 2aI are labelled as I; while those of 2aII as II. Figure S9. Partial views or the 1H-NMR spectrum of 2b in CD2Cl2 at 182 K, showing the presence of two sets of superimposed signals suggesting the presence of two isomers [2bI and 2bII (major and minor components, respectively)]. The resonances due to the allylic protons of 2bI are labelled as I; while those of 2bII as II. Figure S10. Partial views or the 1H-NMR spectrum of 2c in CD2Cl2 at 182 K, showing the presence of two sets of superimposed signals suggesting the presence of two isomers [2cI and 2cII (major and minor components, respectively]. The resonances due to the allylic protons of 2cI are labelled as I; while those of 2cII as II. Figure S11. 1H-NMR spectra of 3a in CD2Cl2 at 298 K (top), 273 K (middle) and 182 K (bottom). Partial views of the spectrum registered at 182 K are shown as insets to illustrate the presence of several sets of superimposed signals of which those labelled as I and II correspond to the two major isomers (hereinafter referred to as 3aI and 3aII) present in solution. Figure S12. 1H-NMR spectrum of compound 3c in CD2Cl2 at 182 K, showing, the presence of two sets of superimposed signals due to isomers 3aI and 3aII (major and minor components, respectively), with high abundance. Other minor peaks labelled as III, suggest the co-existence of an additional isomer (3aIII) (top) and [1H-1H]-NOESY spectrum of 3a at 182 K in CD2Cl2 (bottom). Figure S13. 1H -NMR spectrum of 3b in CD2Cl2 at 182 K, showing the presence of two isomers (3bI and 3bII (major and minor components, respectively), with high abundance. Figure S14. Partial view of the 1H-NMR spectrum of 3c in CD2Cl2 at 182 K, the presence of two isomers (3cI and 3cII (major and minor components, respectively), with high abundance. Figure S15. Optimized geometries of the eight isomers (A-H) of compound 3a. 3. Supplementary Tables (S1–S11): Table S1. Final atomic coordinates of the optimized geometry of the endo-, cis-N, syn- isomer of 3a (type A in Figure 3 and Figure S15). Table S2. Final atomic coordinates of the optimized geometry of the endo-, cis-N, anti- isomer of compound 3a (type B in Figure 3 and Figure S15). Table S3. Final atomic coordinates of the optimized geometry of the isomer endo-, trans-N, syn- isomer of compound 3a (type C in Figure 3 and Figure S10). Table S4. Final atomic coordinates of the optimized geometry of isomer endo-, trans-N, anti- isomer of compound 3a (type D in Figure 3 and Figure S15). Table S5. Final atomic coordinates of the optimized geometry of the exo-, cis-N, syn- isomer of 3a (type E in Figure 3 and Figure S15). Table S6. Final atomic coordinates of the optimized geometry of the exo-, cis-N, anti- isomer of compound 3a (type F in Figure 3 and Figure S15). Table S7. Final atomic coordinates of the optimized geometry of the isomer exo-, trans-N, syn- isomer of compound 3a (type G in Figure 3 and Figure S15). Table S8. Final atomic coordinates of the optimized geometry of isomer exo-, trans-N, anti- isomer of compound 3a (type H in Figure 3 and Figure S15). Table S9. Summary of the characteristic of the isomers (A–H) of 3a together with calculated electronic energies in CH2Cl2, the variation of the calculated energies in relation to the most stable isomer (ΔE) and the results obtained from the Botlzmann’s distribution at 298.15 K and 182.0 K. Table S10. Atomic composition of frontier molecular orbitals and energies (au) for isomers A–H of compound 3a. Table S11. Fragment charges, from the Natural Population analysis for isomers A–H of compound 3a.

Author Contributions

All the authors contribute equally except for the X-ray diffraction studies. (M.F.B. and T.C.)

Funding

This research was funded by Ministerio de Ciencia e Innovación of Spain, Grants: CTQ2015-65040P (subprogram BQU) and PGC2018-093863-B-C21.

Conflicts of Interest

The authors declare no conflict of interest.

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Figure 1. Three different types of compounds containing Pt(II) (A), Ru(II) (B) or Pd(II) (C) and 3-methoxyimino-2-susbtituted-3H-indoles as ligands [21,22,23].
Figure 1. Three different types of compounds containing Pt(II) (A), Ru(II) (B) or Pd(II) (C) and 3-methoxyimino-2-susbtituted-3H-indoles as ligands [21,22,23].
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Scheme 1. Synthesis of compounds 2a–2c and 3a–3c and atom numbering pattern for the carbon atoms of the allylic backbone: i) [Pd(η3-C3H5)(μ-Cl)]2, ii) [Pd(η3-1-PhC3H4)(μ-Cl)]2 in CH2Cl2 at 298 K and using a molar ratio Pd(II):ligand = 1:1.
Scheme 1. Synthesis of compounds 2a–2c and 3a–3c and atom numbering pattern for the carbon atoms of the allylic backbone: i) [Pd(η3-C3H5)(μ-Cl)]2, ii) [Pd(η3-1-PhC3H4)(μ-Cl)]2 in CH2Cl2 at 298 K and using a molar ratio Pd(II):ligand = 1:1.
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Figure 2. Schematic view of the two isomeric forms (A) (endo-) and (B) (exo-) of compounds [Pd(η3-C3H5){C8H3N-2-(C6H4-4-R1)-3-NOMe-5-R2}Cl] [R1 = OMe and R2 = H (2a), R1 = R2 = H (2b) or R1 = H, R2 = Cl (2c)].
Figure 2. Schematic view of the two isomeric forms (A) (endo-) and (B) (exo-) of compounds [Pd(η3-C3H5){C8H3N-2-(C6H4-4-R1)-3-NOMe-5-R2}Cl] [R1 = OMe and R2 = H (2a), R1 = R2 = H (2b) or R1 = H, R2 = Cl (2c)].
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Figure 3. Schematic view of the different isomeric forms (A–H) of compounds 3a–3c. [R1 = H, R2 = OMe (3a); R1 = R2 = H (3b) or R1 = Cl and R2 = H (3c)], showing the relative arrangement of: a) the central Cβ-Hβ bond of the allylic ligand in relation to the phenyl ring (depicted in deep red) of the indole bicycle (endo- or exo-); b) the substituted carbon of the 1-Ph-C3H4 unit and the indole nitrogen (cis-N, or trans-N) and c) the phenyl ring of the allyl ligand in (syn- or anti-) in relation to the Hβ atom.
Figure 3. Schematic view of the different isomeric forms (A–H) of compounds 3a–3c. [R1 = H, R2 = OMe (3a); R1 = R2 = H (3b) or R1 = Cl and R2 = H (3c)], showing the relative arrangement of: a) the central Cβ-Hβ bond of the allylic ligand in relation to the phenyl ring (depicted in deep red) of the indole bicycle (endo- or exo-); b) the substituted carbon of the 1-Ph-C3H4 unit and the indole nitrogen (cis-N, or trans-N) and c) the phenyl ring of the allyl ligand in (syn- or anti-) in relation to the Hβ atom.
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Figure 4. Molecular structure of [Pd(η3-C3H5){C8H3N-2-(C6H5)-3-NOMe-5-(OMe)}Cl] (2a). Selected bond lengths (in Å) and angles (in deg.): Pd1-Cl1, 2.4815(11); Pd1-N1, 2.124(4); Pd1-C17, 2.189(6); Pd1-C18, 2.127(9); Pd1-C19, 2.072(6); C18-C17, 1.379(7); C19-C18, 1.375(7); Cl1-Pd1-N1; 94.23(10); C17-Pd1-N1, 101.43(19); C19-Pd1-Cl1, 99.15(19); C19-Pd1-C17, 65.2(2).
Figure 4. Molecular structure of [Pd(η3-C3H5){C8H3N-2-(C6H5)-3-NOMe-5-(OMe)}Cl] (2a). Selected bond lengths (in Å) and angles (in deg.): Pd1-Cl1, 2.4815(11); Pd1-N1, 2.124(4); Pd1-C17, 2.189(6); Pd1-C18, 2.127(9); Pd1-C19, 2.072(6); C18-C17, 1.379(7); C19-C18, 1.375(7); Cl1-Pd1-N1; 94.23(10); C17-Pd1-N1, 101.43(19); C19-Pd1-Cl1, 99.15(19); C19-Pd1-C17, 65.2(2).
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Figure 5. Molecular structure of [Pd(η3-1-PhC3H4){C8H3N-2-(C6H5)-3NOMe-5(OMe)}Cl] (3a). Selected bond lengths (in Å) and angles (in deg.): Pd1-Cl1, 2.3734(11); Pd1-N1, 2.115(2); Pd1-C17, 2.118(3); Pd1-C18, 2.118(3); Pd1-C19, 2.159(3); C18-C17, 1.384(5); C19-C18, 1.402(5); Cl1-Pd1-N1, 95.41(7); C19-Pd1-N1, 95.78(12); C17-Pd1-Cl1, 99.77(15); C19-Pd1-C17, 68.17(15).
Figure 5. Molecular structure of [Pd(η3-1-PhC3H4){C8H3N-2-(C6H5)-3NOMe-5(OMe)}Cl] (3a). Selected bond lengths (in Å) and angles (in deg.): Pd1-Cl1, 2.3734(11); Pd1-N1, 2.115(2); Pd1-C17, 2.118(3); Pd1-C18, 2.118(3); Pd1-C19, 2.159(3); C18-C17, 1.384(5); C19-C18, 1.402(5); Cl1-Pd1-N1, 95.41(7); C19-Pd1-N1, 95.78(12); C17-Pd1-Cl1, 99.77(15); C19-Pd1-C17, 68.17(15).
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Figure 6. Molecular structure of the two different molecules (I and II) of [Pd(η3-1-PhC3H4){C8H3N-2-(C6H5)-3-NOMe)}Cl] present in the crystal structure of 3b. Selected bond lengths (in Å) for molecule I: Pd1A- Cl1A, 2.3712(8); Pd1A-N1A, 2.129(2); Pd1A-C16A, 2.113(3); Pd1A-C17A, 2.115(3); Pd1A-C18A, 2.161(3); C16A-C17A,1.410(6); C17A-C18A, 1.388(5); N1A- C1A, 1.309(3); O1A-N2A, 1.381(4); O1A-C15A, 1.434(4) and, for molecule II: Pd1B- Cl1B, 2.3741(13); Pd1B-N1B, 2.120(2); Pd1B-C16B, 2.108(3); Pd1A-C17B, 2.116(4); Pd1B-C18B, 2.141(4); C16B-C17B, 1.393(6); C17B-C18B, 1.416(5); N1B-C1B, 1.299(3); O1B-N2B, 1.375(4); O1B-C15B, 1.430(4). Selected bond angles (in deg.) for molecule I: N1A-Pd1A-Cl1A, 95.70(7); N1A-Pd1A-C18A, 94.75(11); Cl1A-Pd1A-C16A, 99.87(11); C16A-Pd1A-C18A, 68.75(14); C2A-N2A-O1A, 110.3(3); N2A-O1A-C15A, 109.5(3); for molecule II: N1B-Pd1A-Cl1A, 96.00(7); N1A-Pd1A-C18A, 95.52(12); Cl1A-Pd1A-C16A, 99.83(14); C16A-Pd1A-C18A, 69.23(16); C2B-N2B-O1B, 110.7(3) and N2A-O1A-C15A, 109.7(3).
Figure 6. Molecular structure of the two different molecules (I and II) of [Pd(η3-1-PhC3H4){C8H3N-2-(C6H5)-3-NOMe)}Cl] present in the crystal structure of 3b. Selected bond lengths (in Å) for molecule I: Pd1A- Cl1A, 2.3712(8); Pd1A-N1A, 2.129(2); Pd1A-C16A, 2.113(3); Pd1A-C17A, 2.115(3); Pd1A-C18A, 2.161(3); C16A-C17A,1.410(6); C17A-C18A, 1.388(5); N1A- C1A, 1.309(3); O1A-N2A, 1.381(4); O1A-C15A, 1.434(4) and, for molecule II: Pd1B- Cl1B, 2.3741(13); Pd1B-N1B, 2.120(2); Pd1B-C16B, 2.108(3); Pd1A-C17B, 2.116(4); Pd1B-C18B, 2.141(4); C16B-C17B, 1.393(6); C17B-C18B, 1.416(5); N1B-C1B, 1.299(3); O1B-N2B, 1.375(4); O1B-C15B, 1.430(4). Selected bond angles (in deg.) for molecule I: N1A-Pd1A-Cl1A, 95.70(7); N1A-Pd1A-C18A, 94.75(11); Cl1A-Pd1A-C16A, 99.87(11); C16A-Pd1A-C18A, 68.75(14); C2A-N2A-O1A, 110.3(3); N2A-O1A-C15A, 109.5(3); for molecule II: N1B-Pd1A-Cl1A, 96.00(7); N1A-Pd1A-C18A, 95.52(12); Cl1A-Pd1A-C16A, 99.83(14); C16A-Pd1A-C18A, 69.23(16); C2B-N2B-O1B, 110.7(3) and N2A-O1A-C15A, 109.7(3).
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Scheme 2. Catalytic allylic alkylation of cinnamyl acetate with sodium diethyl 2-methylmalonate under study (see also footnote a in Table 2).
Scheme 2. Catalytic allylic alkylation of cinnamyl acetate with sodium diethyl 2-methylmalonate under study (see also footnote a in Table 2).
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Scheme 3. Part of the mechanism for the palladium catalyzed allylic alkylation of (E)-3-phenyl-2-propenyl (cinnamyl) acetate using soft nucleophiles [L1 and L2 are two monodentate ligands or a bidentate ligand, S, the solvent, and Nu− the nucleophile). ISi represent the intermediate species formed and the superscript i (i = I, II, III, etc.) refer to the different isomers that could co-exist in solution. (These ISi species may undergo the attack of the nucleophile (Nu−) on different sites and/or at different rates).
Scheme 3. Part of the mechanism for the palladium catalyzed allylic alkylation of (E)-3-phenyl-2-propenyl (cinnamyl) acetate using soft nucleophiles [L1 and L2 are two monodentate ligands or a bidentate ligand, S, the solvent, and Nu− the nucleophile). ISi represent the intermediate species formed and the superscript i (i = I, II, III, etc.) refer to the different isomers that could co-exist in solution. (These ISi species may undergo the attack of the nucleophile (Nu−) on different sites and/or at different rates).
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Table
Table 1. Crystal data and details of the refinement of the crystal structures of compounds [Pd(η3-1-R3C3H4){C8H3N-2-(C6H4-4-R1)-3-NOMe-5-R2}Cl] with R3 = H, R2 = OMe (2a); R3 = Ph, R2 = OMe and R1 = H (3a) and R2 = R1 = H (3b).
Table 1. Crystal data and details of the refinement of the crystal structures of compounds [Pd(η3-1-R3C3H4){C8H3N-2-(C6H4-4-R1)-3-NOMe-5-R2}Cl] with R3 = H, R2 = OMe (2a); R3 = Ph, R2 = OMe and R1 = H (3a) and R2 = R1 = H (3b).
2a3a3b
Empirical formulaC19H19ClN2O2PdC25H23ClN2O2PdC24H21ClN2OPd
Formula weight449.21525.30495.28
Crystal sizes/mm × mm × mm0.20 × 0.10 × 0.100.20 × 0.10 × 0.100.20 × 0.10 × 0.12
Crystal systemMonoclinicMonoclinicTriclinic
Space group C2/cP21/cP-1
a/Å18.953(10)14.461(4)9.813(3)
b/Å7.137(3)15.481(4)14.180(4)
c/Å28.722(8)10.096(4)16.556(3)
α/deg.90.090.098.97(2)
β/deg.108.87(3)97.08(2)103.94(2)
γ/deg.90.090.098.88(2)
T/K293(2)293(2)293(2)
λ/Å0.710730.710730.71073
V/Å33676(3)2243.0(12)2163.8(10)
Z844
Dcalc/mg × m31.6231.5561.520
F(000)180810641000
μ/mm−11.1690.9710.998
Θ range for data collection/deg.from 2.271 to 32.345from 2.677 to 30.875from 1.761 to 30.361
N. of collected reflections38611938018112
N. of unique reflections, [Rint]3866 [0.0543]5572 [0.0275]9882 [0.0207]
N. of parameters/N. of restrains214/6283/0524/0
R indices, [I > 2 σ(I)]R1 = 0.0534,
wR2 = 0.1652		R1 = 0.0428,
wR2 = 0.1013		R1 = 0.0424,
wR2 = 0.1049
R indices (all data) R1 = 0.0608,
wR2 = 0.1719		R1 = 0.0446,
wR2 = 0.1030		R1 = 0.0462,
wR2 = 0.1097
Table
Table 2. Results of the catalytic allylic alkylation of cinnamyl acetate with sodium diethyl-2-methylmalonate using a mixture of [Pd(η3-C3H5)(μ-Cl)]2 and the corresponding ligand. a.
Table 2. Results of the catalytic allylic alkylation of cinnamyl acetate with sodium diethyl-2-methylmalonate using a mixture of [Pd(η3-C3H5)(μ-Cl)]2 and the corresponding ligand. a.
Entry 1LigandT (h)Conversion 2 (%)Molar Ratio 3
4:5:6
I1a248976:6:18
II1b248774:7:19
III1c249183:7:10
IV1a96>9988:8:4
V1b96>9991:6:2
VI1c96>9992:9:0
1 Experimental conditions: at room temperature, tetrahydrofuran (THF) solutions of the corresponding ligand (1a–1c) (5.0 × 10−3 mmol in 1 mL), [Pd(η3-C3H5)(μ-Cl)]2 (2.5 × 10−3 mmol in 1 mL) the allylic substrate (0.5 mmol in 1 mL), and sodium diethyl 2-methylmalonate, (1.0 mmol in 2 mL) were mixed in that precise order and stirred for 24 or 96 h. 2 Analyzed by gas chromatography. 3 Product distribution: linear trans-(E) alkylation product (4), branched product (5) and 1-cinnamyl-3-ethyl-2-methylmalonate (6).

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Tomé, M.; Grabulosa, A.; Rocamora, M.; Aullón, G.; Font-Bardía, M.; Calvet, T.; López, C. Synthesis, Characterization, Solution Behavior and Theoretical Studies of Pd(II) Allyl Complexes with 2-Phenyl-3H-indoles as Ligands. Catalysts 2019, 9, 811. https://doi.org/10.3390/catal9100811

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Tomé M, Grabulosa A, Rocamora M, Aullón G, Font-Bardía M, Calvet T, López C. Synthesis, Characterization, Solution Behavior and Theoretical Studies of Pd(II) Allyl Complexes with 2-Phenyl-3H-indoles as Ligands. Catalysts. 2019; 9(10):811. https://doi.org/10.3390/catal9100811

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Tomé, Maria, Arnald Grabulosa, Mercè Rocamora, Gabriel Aullón, Mercè Font-Bardía, Teresa Calvet, and Concepción López. 2019. "Synthesis, Characterization, Solution Behavior and Theoretical Studies of Pd(II) Allyl Complexes with 2-Phenyl-3H-indoles as Ligands" Catalysts 9, no. 10: 811. https://doi.org/10.3390/catal9100811

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