(Dicyclohexyl(2-(dimesitylboryl)phenyl)phosphine: en route to stable frustrated Lewis pairs-hydrogen adducts in water

1 Introduction

Frustrated Lewis pairs (FLPs) is a powerful yet simple concept to activate various chemical bonds through their heterolytic splitting. In order to achieve “frustration”, i.e. prevent formation of classical Lewis adducts, Lewis acids and the Lewis bases with sterically bulky substituents are needed. Various parameters such as acid and base strengths, and steric hindrance of the reactive centers can be varied to affect reactivity, catalytic activity, and selectivity of FLPs. FLP chemistry emerged as a powerful tool for activation of a broad range of small molecules, but, primarily, of molecular hydrogen (H₂). Particularly, many breakthroughs have been accomplished in the hydrogenation of organic molecules catalyzed by FLPs [1], [2], [3], [4], [5], [6]. Parahydrogen-induced polarization (PHIP) represents another application of FLPs to activate H₂. PHIP is a phenomenon of achieving nuclear magnetic polarization states well above the thermal level through interaction with molecular hydrogen that is enriched with parahydrogen, one of its spin isomers [7], [8], [9]. To achieve high PHIP levels, para-H₂ should lose symmetry upon addition to a substrate or a catalyst and the mechanism of parahydrogen addition should be pairwise. Hyperpolarization can be observed with intensities increased by orders of magnitude of para-H₂-originated ¹H nuclei as well as other magnetically coupled nuclei, such as ¹³C, ¹⁵N, etc. In a typical protocol, parahydrogen is initially added to a heterogeneous or homogeneous metal center along with a substrate molecule. Then either parahydrogen is transferred to the substrate molecule, or magnetization can be transferred via reversible coordination of parahydrogen and a substrate molecule to the metal center (SABRE) [10].

We and others have recently demonstrated that PHIP can be observed in metal-free conditions upon addition of parahydrogen to ansa-aminoboranes, for example, 1 [11] (Fig. 1). In a later publication we conducted a detailed study of PHIP observed with other type of ansa-aminoboranes, compounds 2a–c, and concluded that the relatively low levels of achieved hyperpolarization (<20-fold signal intensity enhancements) were caused by the presence of quadrupole ¹⁴N (nuclear spin 1) and ¹¹B (nuclear spin −3/2) nuclei that drastically diminish polarized signals intensities due to fast spin relaxation. To overcome this limitation, it was proposed to replace ¹⁴N nucleus with ¹⁵N or ³¹P both of which have spin 1/2 with longer typical relaxation times [12]. Herein we report synthesis of previously unknown (dicyclohexyl(2-(dimesitylboryl)phenyl)phosphine 6 and studies of its interaction with molecular hydrogen and water.

Fig. 1:

Ansa-amino- and ansa-phosphinoboranes reported to activate molecular hydrogen.

Phosphinoborane 3 was the first FLP reported to split H₂ [13]. Since then, other types of phosphinoboranes, particularly, ansa-phosphinoboranes with saturated [14], [15], [16], [17] and unsaturated [18], [19] linkers between the P and B atoms have been demonstrated to react with H₂. Among them, 2-phosphinophenylboranes 4a–c were prepared by a sequence of electrocyclic ring closure and oxidation reactions [18], [19]. Besides this, various 2-phosphinophenylboranes have previously been synthesized and used as ligands for transition metal complexes [20], [21], [22], [23], [24], [25].

2 Results and discussion

Ansa-phosphinoborane 6 was synthesized in 67% yield by a one-pot procedure from commercially available phosphine 5 (Fig. 2). Unlike in 4a–c, there is no dative bond between B and P atoms (3.1773 (17) Å distance) in 6 as established by the single crystal X-ray diffraction analysis (Fig. 3). In CD₂Cl₂, ¹¹B and ³¹P NMR signals of 6 appear as singlets at 75.68 (broad) and −0.64 ppm, revealing that there is no P–B interaction [26]. Because 6 is structurally close to the previously reported ansa-aminoborane 2a and proton affinities of isostructural N,N-dimethylaniline and dimethylphenylphosphine are close [27], we expected to detect 7, the product of dihydrogen addition to 6. However, prolonged exposure of a solution of 5 to pressurized hydrogen (10 bar) in a gas-tight NMR tube revealed no evidence of the phosphonium borate 7. To our surprise, 6 did not react with water as well, neither at ambient not at elevated temperatures.

Fig. 2:

Synthesis of ansa-phosphinoborane 6, and its inertness to hydrogen or water.

Fig. 3:

(a) Structure of 6 in the solid state based on XRD data. Ortep drawing, thermal ellipsoids at the 50% probability level, P–B distance 3.1773(17) Å. (b) Optimized molecular geometry of 6in vacuo, DFT, ωB97X-D/6-311G(d,p), P–B distance 3.18179 Å.

To rationalize the observed failure of the addition, we examined thermodynamics of formation of 7 and 8via DFT calculations. The optimized geometry of 6 (Fig. 3b) is in good agreement with the one obtained from the single-crystal X-ray diffraction analysis (Fig. 3a). For both 7 and 8 we analysed endo and exo isomeric forms, with and without an intramolecular PH···XB (X=H or OH) bond, respectively (Fig. 4). Intramolecular H···H bonding appears to be crucial for observation of PHIP by ansa-aminoboranes. Therefore, our finding that, in terms of solution Gibbs free energies, endo-7 is by ca. 2 kcal mol⁻¹ more stable than exo-7 shows that the chosen scaffold is a promising starting point for further studies. Previously reported H₂ adducts of 4a and 4b also exist as endo-forms [18]. A very close analog of 6, (diisopropyl(2-(dimesitylboryl)phenyl)phosphine, was previously reported along with its HF adduct. Collected NMR data indicated the presence of an intramolecular H···F bond [28]. For the water adduct 8, however, we found that the exo-form is favored by 3–5 kcal mol⁻¹ over the endo-form. In contrast to H₂, adducts of H₂O and P/B FLPs are much less studied, but available XRD data point to a preference of the PH···(OH)B bond formation [29] that can be outweighed by strong steric effects [30]. The thermodynamics of the formation of 7 and 8 were found to be endergonic, in agreement with experimental observations. It was most surprising, however, that, in benzene as a solvent, hydrogen addition to 6 is by only 2.6 kcal mol⁻¹ more endergonic than water addition. Moreover, addition of hydrogen become energetically more favorable in more polar solvents such as methanol or acetonitrile. As is shown in Table 1, 7 gets progressively stabilized with increasing polarity of the solvent, an effect we have previously observed for a hydrogen adduct of an ansa-aminoborane [31]. At the same time, the Gibbs energy of the formation of 8 remains nearly unchanged.

Fig. 4:

Optimized geometries of 7 and 8in vacuo. DFT, ωB97X-D/6-311G(d,p).

The reported solution phase Gibbs free energies are based on ωB97X-D/6-311++G(3df,3pd) electronic energies, and all additional terms were obtained at the ωB97X-D/6-311G(d,p) level.

Sensitivity of FLPs to moisture is considered as one of the serious limiting factors in the widespread application of FLPs as hydrogenation catalysts [32]. The majority of FLP-based catalysts contain highly Lewis acidic organoboron compounds. Based on the bond dissociation energies, the reaction B–H+H–O→B–O+H–H is exothermic by 111 kcal mol⁻¹ (standard state enthalpy at 298 K) [33]. It is not surprising then that water molecules are bound much stronger than H₂ in FLPs structures, thus deactivating the catalysts. To cope with this problem, organoaluminium and silicon compounds were successfully utilized as scavengers of water [32]. Alternatively, the high oxophilicity of boron centers can be suppressed by hindrance its atom with sterically bulky substituents [34]. Both front and back strain allow strong steric discrimination of an OH substituent over a compact H atom [35]. Apparently, this scenario is realized in the case of 6 that contains sterically bulky 2-(dicyclohexylphospino)phenyl and mesityl groups around the Lewis acidic center. Although these and other approaches [36] were successfully used in catalysis, to the best of our knowledge, no FLP-H₂ adduct formation in the presence of water have been reported.

Further experimental and computational studies on water-tolerant intramolecular FLPs are in progress, especially, with regard to PHIP applications in aqueous media such as for vivo magnetic resonance imaging.

3 Experimental section

Starting materials were purchased from Sigma-Aldrich and used as received. All solvents were dried using a Vac solvent purification system and stored over 3 Å molecular sieves. Deuterated solvents were dried by standing over 3 Å molecular sieves and used without additional purification. Synthesis was performed under argon atmosphere by a conventional Schlenk technique or in a glove box. Hydrogen addition at 10 bar was carried out in gas-tight NMR tubes (QPV tubes from Wilmad). Schlenk vessels were equipped with gas-tight Teflon valves and Glindemann PTFE sealing rings. NMR spectra were recorded at Varian Mercury 300 (³¹P, ¹³C) or Varian Inova 500 (¹H, ¹¹B) spectrometers at 27°C and referenced to the residual ¹H/¹³C resonances of the deuterated solvent and reported as parts per million relative to tetramethylsilane. ³¹P and ¹¹B NMR spectra were referenced externally to 85% H₃PO₄ at 0 ppm, and BF₃·Et₂O at 0 ppm, respectively.

4 Supporting information

NMR spectra of 6 and computational details (method description, total energy and geometry data) associated with this article can be found in the online version (DOI: https://doi.org/10.1515/znb-2017-0133).