*2.2. Crystallographic Characterization of Sulfonated Salan Ligands 1–5 and Palladium (II) Complexes of PrHSS (***7***) and BuHSS (***8***)*

## 2.2.1. Sulfonated salan ligands **1**–**5**

Although complexes of sulfonated salens and non-sulfonated salans have been used already as homogeneous catalysts, the water-soluble Pd (II) complexes of sulfonated salans were first synthesized and applied in our laboratory to catalyse C–C cross-coupling reactions in water. Ligands **1**–**5** were obtained by an improved method consisting of sulfonation of the diamine precursors **21**–**25**, and Pd (II) complexes **6**–**10** were synthesized in reactions of the ligands with (NH4)2[PdCl4]. The compounds obtained in this work have not been characterized earlier by SC-XRD despite the considerable structural differences that can be expected between the complexes depending on the nature and size of the bridging unit of their sulfosalan ligand. For this reason, we undertook a structural study of the ligands and complexes available in the form of crystals suitable for X-ray diffraction measurements. Luckily, good quality crystals could be grown from water in the cases of **1** × 2H2O, PrHSS (**2**), BuHSS (**3**), (±)-*trans*-CyHSS (**5b**), **5ca** and **5cb**. Unfortunately, we could not obtain crystals of dPhHSS (**4**) from water and this latter compound was crystallized from wet dimethylsulfoxide (DMSO). Na2[Pd(PrHSS)] (**7**) and Na2[Pd(BuHSS)] (**8**) were dissolved in 1M KOH solution layered by 2-propanol. All efforts to grow crystals of **6**, **9** and **10** remained so far unsuccessful.

Full details of the crystallographic results are outside the scope of this manuscript but are amply described in the Supplementary Material. Nevertheless, a few basic findings are mentioned below.

Scarcely any similar compounds have been reported that could be compared to our new structures. However, in such cases, a great degree of similarity is found. For example, the major difference in the bond distances of **1** × 2H2O (Figure 1) and its already known solvomorph [44], **1** × DMSO, is in the C8–C8(i) bond length (1.529(11) Å vs. 1.495 Å). The starting compound for the synthesis of PrHSS (**2**), i.e., *N*,*N*'-*bis*(2-hydroxybenzyl)-1,3-diaminopropane, PrHS, was previously crystallized with various aromatic polycarboxylates [48] and SC-XRD studies revealed the protonation of the secondary amine groups of PrHS, similar to the case of PrHSS (**2**) (Figure 2). Comparison of the structure of n-K4[μ8-BuHSS][μ2-H2O]4[H2O]6 published by us earlier [46] to the one of **3** in this study (Figure 3), shows, that the N1–C7–C1 angles are almost the same (114.28◦ and 114.4◦) in the two molecules, and only the positions of the aromatic groups are different (Figure S15). Superposition of the structures of the salan ligand, *meso* (RS,SR)-*N,N*'-*bis*(2-hydroxybenzyl)-1,2-diphenyl-1,2-diaminoethane [49] and its sulfonated product, dPhHSS (**4**) (Figure 4) also shows high degree of similarity (Figure S20) and proves that the starting salen underwent hydrogenation as well as sulfonation in the *p-*position relative to the phenolic oxygen. The major difference between the structures of **5b** (Figure 5) and its starting material for synthesis, i.e., (±)-*trans*-CyS [50] is in the position of the aromatic rings (Figure S23). Perhaps the most important information is that, during the synthesis of *cis*-CyHSS × 2H2O (**5ca**) (Figure 5), the *cis*-conformation in the Schiff base formed in the reaction of salicylaldehyde and *cis*-1,2-diaminocyclohexane is retained throughout hydrogenation and sulfonation. An interesting observation is that, when a racemic mixture of *cis*-CyHSS and *trans*-CyHSS was subjected to crystallization from water, the procedure yielded only crystals of *cis*-CyHSS (**5cb**) (Figure 5). The cyclohexyl ring of the sulfonated product *cis*-CyHSS overlaps precisely with the cyclohexyl ring in *N,N'*-di-5-nitrosalicylidene-(*R,S*)-l,2-cyclohexanediamine, published by Desiraju et al. [51] (see superposition of the molecules, Figure S27).

**Figure 2.** Capped sticks representation of **2** × 5.5H2O. Lattice water molecules are omitted for clarity.

**Figure 3.** Capped sticks representation of **3**. Symmetry code: (i) –x, 1–y, –z; *Z*' = 0.5.

**Figure 4.** Capped sticks representation of **4** × H2O × DMSO. Solvents molecules are omitted for clarity. Symmetry code: (i) 1–x, 1–y, 1–z.

Powder diffraction patterns of **1** × 2H2O and **3** were calculated from the cell parameters of the crystals obtained from water and the ones measured experimentally on the powdery products yielded by the synthesis; a good agreement was found with the experimentally determined diffractograms (Figures S5 and S16). This shows that the direct products of syntheses and the crystals grown from water have the same composition.

It is the general characteristics of the crystals of **1**–**5** that they contain various numbers of solvent molecules, in most cases water. Due to the large number of water molecules and to the presence of O- and N-atoms in the ligands, strong hydrogen bonds are formed within the lattices. In addition to the hydrogen bonds, the crystal architecture is also stabilized by the π−π interactions between the aromatic rings. Quantitative details are included in Tables S1–S7 and shown on the relevant crystal packing diagrams of **1**–**5** in Supplementary Material.

**Figure 5.** Structures of (±)-*trans-*CyHSS × 7H2O (**5b**; P1), *cis*-CyHSS × 2H2O (**5ca**; P21/c) and *cis*-CyHSS × 6H2O (**5cb**; C2/c). Water molecules are omitted for clarity.

#### 2.2.2. Palladium (II) Complexes of PrHSS (**7**) and BuHSS (**8**)

Crystals of K2[Pd(PrHSS)] (**7**- ) K2[Pd(BuHSS)] (**8**- ) were obtained from solutions of Na2[Pd(PrHSS)] (**7**) and Na2[Pd(BuHSS)] (**8**) in 1M KOH solution layered by 2-propanol and were subjected to SC-XRD measurements at 5 ◦C. The packing diagrams of the two complexes reveal that the complexes are placed within the lattice in layers and that the sulfosalan complexes are held together by inorganic polymer chains (Figures S32–S35). In the case of both complexes, the 2D structures are shaped by the electrostatic and van der Waals interactions between the K<sup>+</sup> ions and the O-atoms of the sulfonate groups of the ligand and water molecules, together with the hydrogen bonds within the lattice. Similar polymeric chains were detected by us in crystals of the n-K4[μ8-BuHSS][μ2-H2O]4[H2O]6 sulfosalan [46] and in the cases of Ni(II) and Cu(II) complexes of *bis*(salicylidene)-1,2-diaminocyclohexane, CyS [52].

Diffraction measurements were made on several crystals of both complexes at 150 K and at room temperature. Since the crystals were twinned and the polymer chains were flexible, despite all our efforts, all *R* values were higher than 10%, together with *wR2*-s > 25%. Due to these errors, the bond lengths and angles determined for the complexes are not suitable for discussion. Nevertheless, the SC-XRD measurements yielded clear atomic connectivities in both cases (Figure 6) and, together with the spectroscopic data, prove the structures of the complexes. These are the first solid state structures obtained for Pd (II)–sulfosalan complexes that, despite all uncertainties, show clearly the steric differences imposed by C3 and C4 bridging alkyl chains in Pd (II)–sulfosalan complexes.

**Figure 6.** Capped sticks views of K2[Pd(PrHSS)] (**7**- ). Symmetry code: (i) +x, 1/2–y, +z and K2[Pd(BuHSS)] (**8**- ). Solvents and the flexible polymer chains linked together by K<sup>+</sup> and water molecules are omitted for clarity.

#### *2.3. Catalytic Properties of the Pd(II)–Sulfosalan Complexes in Suzuki–Miyaura Cross-Coupling Reactions*

Earlier, we have established that some of the Pd (II)-sulfonated salan complexes were active catalysts for the Suzuki–Miyaura cross-coupling reactions in aqueous media. The reactions could be performed under aerobic conditions, and the catalysts showed outstanding stability in aqueous solutions. One of the aims of the present study was the comparison of catalytic properties of Pd (II)-sulfonated salan complexes with various linker groups, L, in the Suzuki–Miyaura cross-coupling and the exploration of the usefulness of the best catalysts for the reactions of a wide range of substrates under various conditions. For this purpose, in addition to the already known sulfosalans, we synthesized new ligands of such types starting with *cis*- and *trans*-isomers of 1,2-cyclohexanediamine and developed synthetic procedures for **7** and **9**, too.

For the comparison of the Pd (II)–sulfosalan catalysts **6**–**10**, the Suzuki–Miyaura cross-coupling of iodobenzene and phenylboronic acid were chosen as a standard reaction (Figure 7). With all catalysts, fast and clean reactions were observed. The reaction mixtures retained their original yellow colour throughout the reaction, and no metal precipitation was detected. Conversions (calculated for iodobenzene) were established by gas chromatography after extraction of the reaction mixtures with CHCl3. The results are shown Figure 8.

**Figure 7.** Suzuki–Miyaura cross-coupling of iodobenzene and phenylboronic acid catalysed by Pd (II)–sulfosalan complexes in water.

**Figure 8.** Comparison of the catalytic activity of Pd (II)–sulfosalan complexes **6**–**10** in the Suzuki–Miyaura cross-coupling reaction of iodobenzene and phenylboronic acid: Conversions are calculated for iodobenzene. Catalysts: Na2[Pd(HSS)] (**6**), Na2[Pd(PrHSS)] (**7**), Na2[Pd(BuHSS)] (**8**), Na2[Pd(dPhHSS)] (**9**), *rac*-Na2[Pd(CyHSS)] (**10a**), Na2[Pd(*trans*-CyHSS)] (**10b**) and Na2[Pd(*cis*-CyHSS)] (**10c**). Conditions: 2.0 <sup>×</sup> <sup>10</sup>−<sup>8</sup> mol catalyst, 5.0 <sup>×</sup> <sup>10</sup>−<sup>4</sup> mol iodobenzene, 7.5 <sup>×</sup> <sup>10</sup>−<sup>4</sup> mol phenylboronic acid, 5 <sup>×</sup> <sup>10</sup>−<sup>4</sup> mol Cs2CO3, solvent: H2O (V <sup>=</sup> 3 mL), T <sup>=</sup> <sup>80</sup> ◦C and t <sup>=</sup> 30 min.

Figure 8 shows that there are substantial differences in the catalytic activities of the various Pd (II)–sulfosalan complexes, with Na2[Pd(HSS)] (**6**) being the least effective (14% conversion) and Na2[Pd(dPhHSS)] (**9**) being the most active (93% conversion) catalyst. The exact reaction mechanism of the Suzuki–Miyaura cross-couplings catalysed by Pd (II)–sulfosalan complexes in aqueous media is presently unknown. For the reaction of Na2[Pd(HSS)] (**6**) and Na2[Pd(BuHSS)] (**8**) with H2, we obtained evidence of the need for a vacant coordination site for the oxidative addition of H2 [43,44]. In the present case, the catalytic activity increased with increasing length of the linker chain in the order **6** (14%) < **7** (35%) < **8** (72%). This is also the order of increasing flexibility of the coordination sphere around the Pd (II) central ion as can be judged also from the solid state structures of **7** and **8** (Figure 7). The Pd (II) complexes with sulfosalan ligands derived from 1,2-diaminocyclohexanes (**10a**–**10c**) catalysed the Suzuki–Miyaura cross-coupling of iodobenzene and phenylboronic acid with equal activities (58%, 60% and 60%, respectively) which is significantly higher than that of Na2[Pd(HSS)] (**6**), having also a two-carbon linker group between the N-atoms of the ligand. The conversion data also show that the catalytic performance is insensitive to the stereochemistry of the ligands in **10b** and **10c**. Finally, the outstandingly high catalytic activity of Na2[Pd(dPhHSS)] (**9**) (which also contains a two-carbon linker group in its ligand) may stem from the space requirement of the two phenyl substituents. All these observations are in agreement with the assumption that longer and more substituted linker groups in the sulfosalan ligands may facilitate de-coordination of one of the phenolate oxygens and, in such a way, may lead to creation of a vacant coordination site on Pd (II) which is manifested in higher catalytic activities.

The catalytic properties of the two most active catalysts for the Suzuki–Miyaura cross-coupling reactions, Na2[Pd(dPhHSS)] (**9**) and Na2[Pd(BuHSS)] (**8**), were studied in some detail, mostly from a synthetic viewpoint.

Table 1 shows conversion of reactions between a variety of aryl halides and arylboronic acids (two heteroarylboronic acids were also included). The data show that **9** is able to catalyse the reaction with very high activity, with turnover frequencies (TOF) up to 40,000 h−<sup>1</sup> (TOF = (mol reacted substrate) (mol catalyst <sup>×</sup> time)<sup>−</sup>1). As generally observed, aryl iodides reacted faster than aryl bromides (entries 1/14, 6/11 and 12/13); however, with extended reaction times, medium to high conversions could be achieved with aryl bromides, too (entries 8, 9, 11 and 16). The catalyst tolerates several common functional groups; however, aryl or hetaryl halides containing good donor atoms for Pd (II) reacted slower (entries 6, 11, 17 and 20).

**Table 1.** Suzuki–Miyaura cross-coupling reactions of various boronic acids with different aryl halides catalysed by Na2[Pd(dPhHSS)].


Conditions: 1.0 × <sup>10</sup><sup>−</sup>6–2.0 × <sup>10</sup>−<sup>8</sup> mol Na2[Pd(dPhHSS)] catalyst, 5.0 × <sup>10</sup>−<sup>4</sup> mol aryl halide, 7.5 × <sup>10</sup>−<sup>4</sup> mol boronic acid derivative, 5.0 <sup>×</sup> <sup>10</sup>−<sup>4</sup> mol Cs2CO3, solvent: H2O (V <sup>=</sup> 3 mL) and T <sup>=</sup> <sup>80</sup> ◦C. <sup>a</sup> Aryl iodide. <sup>b</sup> Aryl bromide. <sup>c</sup> Conversion determined by 1H-NMR.

Since aryl halides have limited solubility in water, in fact, these reactions take place in aqueous-organic biphasic systems and the actual concentration of the substrates in the catalyst-containing aqueous phase may be very low—this can also lead to low conversions and TOF-s and may mask the chemical differences in reactivity.

Under otherwise identical conditions, the reaction rate depends on the arylboronic acid to aryl halide molar ratio. This is exemplified in Table 2. In view of the data in the table, in most of our experiments, a 50 mol % excess of a boron derivative over the aromatic halide was used.

**Table 2.** Effect of the (phenylboronic acid)/(iodobenzene) ratio on the reaction rate of their Suzuki–Miyaura cross-coupling catalysed by Na2[Pd(dPhHSS)].


Conditions: 2.0 × <sup>10</sup>−<sup>8</sup> mol Na2[Pd(dPhHSS)], 5.0 × <sup>10</sup>−<sup>4</sup> mol iodobenzene, 5.0 × <sup>10</sup>−<sup>4</sup> mol Cs2CO3, solvent: H2O (V = 3 mL), T = 80 ◦C and t = 30 min.

The catalytic performance and substrate scope of Na2[Pd(dPhHSS)] (**9**) and Na2[Pd(BuHSS)] (**8**) are further demonstrated by the data in Tables 3 and 4, respectively. It seems that the chemical nature of the substituents in the boronic acid derivative or in the aryl halide has only a limited influence on the rate of formation of the appropriate biphenyls.


**Table 3.** Suzuki–Miyaura cross-coupling reactions of boronic acid derivatives with bromobenzene and 4-bromoacetophenone.

Conditions: 1.7 × <sup>10</sup>−<sup>7</sup> mol Na2[Pd(dPhHSS)], 5.0 × <sup>10</sup>−<sup>4</sup> mol aryl halide, 1.5 × <sup>10</sup>−<sup>3</sup> mol boronic acid, 5.0 × <sup>10</sup>−<sup>4</sup> mol Cs2CO3, solvent: H2O (V = 3 mL), T = 80 ◦C and t = 1 h.


**Table 4.** Suzuki–Miyaura cross-coupling reactions of 4-tolylboronic and 4-methoxyphenylboronic acids with various aryl halides.

Conditions: 5.0 × 10−<sup>7</sup> mol Na2[Pd(BuHSS)], 5.0 × 10−<sup>4</sup> mol aryl halide, 7.5 × 10−<sup>4</sup> mol 4-tolylboronic acid or 4-methoxyphenylboronic acid, 5.0 × 10−<sup>4</sup> mol Cs2CO3, solvent: H2O (V = 3 mL), T = 80 ◦C and t = 1 h.

Na2[Pd(dPhHSS)] catalysed also the Suzuki–Miyaura cross-coupling of phenylboronic acid with various aryl dihalides; the results are shown in Table 5. It is interesting to see that, with this catalyst, the major (in most cases exclusive) products were the corresponding terphenyl derivatives (entries 2–4). Only in the case of an aryl dihalide with two different halide substituents was a small conversion to the corresponding halogenated biphenyl detected. Such a high selectivity is not generally observed; see the results with the Na2[Pd(BuHSS)] catalyst below.


**Table 5.** Suzuki–Miyaura cross-coupling of phenylboronic acid and aryl dihalides catalysed by Na2[Pd(dPhHSS)].

Conditions: 1.7 × 10−<sup>7</sup> mol [Pd(dPhHSS)], 5.0 × 10−<sup>4</sup> mol aryl dihalide, 1.5 × 10−<sup>3</sup> mol phenylboronic acid, 5.0 × 10−<sup>4</sup> mol Cs2CO3, solvent: H2O (V = 3 mL), T = 80 ◦C and t = 1 h.

It is shown by the data in Table 3 (entries 5 and 10) that both NaBPh4 and KBF3Ph can be used as phenyl group donors in the Suzuki–Miyaura reaction with Na2[Pd(dPhHSS)] as the catalyst. Although both salts are water-soluble, their use results in modest or medium high conversions. Na-tetraphenylborate was used in Suzuki–Miyaura cross-coupling with aryl dihalides catalysed by Na2[Pd(dPhHSS)]; however, the reactions proceeded with low yields (in1hreaction time) and incomplete selectivity (Table 6).

**Table 6.** Suzuki–Miyaura cross-coupling reactions of Na-tetraphenylborate with aryl dihalides catalysed by Na2[Pd(dPhHSS)].


Conditions: 1.7 × 10−<sup>7</sup> mol Na2[Pd(dPhHSS)], 5.0 × 10−<sup>4</sup> mol aryl dihalide, 1.5 × 10−<sup>3</sup> mol NaBPh4, 5.0 × 10−<sup>4</sup> mol Cs2CO3, solvent: H2O (V = 3 mL), T = 80 ◦C and t = 1 h.

The catalytic features of Na2[Pd(dPhHSS)] in the Suzuki–Miyaura cross-coupling of aromatic dihalides were compared to those of Na2[Pd(BuHSS)]; the latter showed the second highest activity (Figure 8) in cross-coupling of phenylboronic acid and iodobenzene. According to the data in Table 7, Na2[Pd(BuHSS)] is also a very active catalyst for this reaction, since in the cases of phenylboronic and 4-tolylboronic acids, uniformly high (close or above 90%) total conversions of the dihalides were achieved (4-methoxyphenylboronic acid reacted less readily). However, although the yield of biphenyls was generally lower than those of the terphenyls, the reactions were far from selective even with aromatic halides containing two identical halogens. The highest biphenyl–terphenyl selectivity was 17:74, obtained in the reaction of 4-tolylboronic acid and 4-bromo-1-iodobenzene.



Conditions: 5.0 × 10−<sup>7</sup> mol Na2[Pd(BuHSS)]; 5.0 × 10−<sup>4</sup> mol aryl dihalide; 1.5 × 10−<sup>3</sup> mol phenylboronic acid, 4-tolylboronic acid or 4-methoxyphenylboronic acid; 5.0 × 10−<sup>4</sup> mol Cs2CO3; solvent: H2O (V = 3 mL); T = 80 ◦C; and t = 1 h.
