Ambiphilic Frustrated Lewis Pair Exhibiting High Robustness and Reversible Water Activation: Towards the Metal-Free Hydrogenation of Carbon Dioxide

The synthesis and structural characterization of a phenylene-bridged Frustrated Lewis Pair (FLP) having a 2,2,6,6-tetramethylpiperidine (TMP) as the Lewis base and a 9-borabicyclo[3.3.1]nonane (BBN) as the Lewis acid is reported. This FLP exhibits unique robustness towards the products of carbon dioxide hydrogenation. The compound shows reversible splitting of water, formic acid and methanol while no reaction is observed in the presence of excess formaldehyde. The molecule is incredibly robust, showing little sign of degradation after heating at 80 °C in benzene with 10 equiv. of formic acid for 24 h. The robustness of the system could be exploited in the design of metal-free catalysts for the hydrogenation of carbon dioxide.

Aminoboranes, first developed by Piers [44] and further studied by Repo and co-workers [6,9,45,46] are therefore FLPs of choice for the reduction of carbon dioxide. However, many of these species exhibit decomposition, notably by protodeborylation, once H2 is activated [6,43]. Also possible is the formation of an iminium ion by abstraction of a hydride in the α position to nitrogen [47], which can occur when electron withdrawing groups, such as perfluoroaryls, are present on boron. In our search for an efficient catalyst for carbon dioxide reduction, we were interested in the design of ambiphilic aminoborane molecules where such degradation pathways would be avoided by containing no hydrogen in α position of the nitrogen or aryl groups on boron. Herein we report the synthesis of 1-(BBN)-2-(TMP)-C6H4 (BBN = 9-borabicyclo[3.3.1]nonane and TMP = 2,2,6,6-tetramethylpiperidine), which exhibits unique robustness.

Synthesis and Characterization of 1-(BBN)-2-(TMP)-C6H4
The synthesis of species 1-(BBN)-2-(TMP)-C6H4 (1) is illustrated in Scheme 1. It is conveniently prepared by first reacting lithium 2,2,6,6-tetramethylpiperidine with iodobenzene to give 1-I-2-(TMP)-C6H4. Lithium-halogen exchange between n-BuLi and the latter product gave 1-Li-2-(TMP)-C6H4 [48,49], which was trapped with Br-BBN to give the desired compound 1 in 73% yield. The 1 H-and 13 C{ 1 H} NMR spectra of species 1 displays different chemical shifts for the methyl groups pointing away (0.83 ppm) and towards (1.26 ppm) boron, suggesting that rotation around the nitrogen-aryl bond is slow on the NMR timescale. In contrast, the BBN moiety exhibits fast rotation about the boron-aryl bond on the NMR timescale, as evidenced by the observation of only three carbon resonances for the BBN fragment.
Crystals of 1 suitable for single-crystal X-ray diffraction analysis have been grown from hexanes at −35 °C. The structure and the selected bond lengths and bond angles are shown in Figure 1. The sum of internal bond angles around the boron atom (359.2°) is indicative of a trigonal planar conformation. The long B-N distance of 3.053(1) Å indicates no interaction between the Lewis acid and the Lewis base functionalities. Moreover, the X-ray crystal structure of 1 shows that both six-membered cycles of the BBN moiety adopt a chair conformation. The TMP cycle also adopts a chair conformation with two methyl groups pointing toward the boron moiety.

Reactivity of 1-(BBN)-2-(TMP)-C6H4 with Small Molecules
The hydrogenation of carbon dioxide to methanol is a six-electron reduction process that will generate formic acid and formaldehyde as intermediates in addition of generating one equivalent of water, with the end product being methanol, as shown is Scheme 2. A good reduction catalyst therefore needs to show stability towards all of these intermediates and products.
When species 1 is exposed to water, a novel species is observed indicative of the splitting of water (2). The 11 B-NMR signal shifts from 83.4 ppm corresponding to a R3B compound for 1 to 0.0 ppm corresponding to a R3BOH − . The signals of the aliphatic carbons directly linked to the heteroatoms are also consistent with the formation of a zwitterion; the 13 C{ 1 H} NMR signal for C11 and C12, directly linked to the nitrogen, shifts to lower field by 7.6 ppm when those of C16 and C17, directly linked to the boron, shift to higher field by 5.1 ppm. Finally, a resonance is observed in the 1 H-NMR spectrum at very low field (δ = 17.1) for the splitting of water, which is quite similar to the equivalent resonance, observed by Jäkle, for a pyridylferrocene derivative [50] and suggests hydrogen bonding between O and the proton linked to N. It was found that the water adduct can be reverted back to 1 after a solution of 2 in benzene-d6 was stored over 4 Å molecular sieves at room temperature for ca. 12 h. However, when placed in presence of excess water (10 equiv.) for 12 h, 2 shows signs of hydrolysis.
It was possible to obtain crystals of 2 by crystallization from hexanes at −35 °C. The structure is shown in Figure 2. As observed for the crystal structure of 1, the TMP cycle in 2 adopts a chair conformation with two methyl groups of the TMP framework pointing toward the BBN moiety. The sum of internal bond angles around the nitrogen atom (348.5°) indicates a higher degree of pyramidalization compared to 1, which is consistent with the coordination of a proton on nitrogen, which was not located in the Fourier map. Moreover, the N-C1 bond is stretched from 1.442(1) in 1 to 1.490(2) Å. The six-membered rings of the borane also adopt a chair conformation. The geometry around boron is tetrahedral, as expected from a borate moiety, with the B-C6 elongated from 1.576(1) on 1 to 1.666(2) Å.
The reaction between formic acid and 1 generated a novel product, 3, which is reminiscent to the product obtained from the splitting of water. The signals of the aliphatic carbons directly linked to the heteroatoms suggest the formation of a zwitterionic species, as the one observed in 2. According to the numbering scheme used for the structure of 2, the signals of C11 and C12, which are directly linked to the nitrogen show a 13 C-NMR shift to lower field by 14.6 ppm while those of C16 and C17, directly linked to the boron, shift to higher field by 7.4 ppm for 3. The signals of C22 and C23, which are equivalent on the 13 C-NMR spectra in 1, exhibit inequivalence in 3 as observed in the case of 2. The 11 B-NMR resonance at δ = 2.1 is also consistent with the formation of a zwitterionic species. The reversibility of the formic acid adduct was also studied and 3 partially (ca. 50%) reverted back to 1 after standing over K2CO3 in a solution of benzene-d6 at room temperature for ca. 12 h. Finally, when placed in presence of excess formic acid (10 equiv.), 3 showed very little degradation (less than 5%) even after heating at 80 °C for 24 h. Methanol also reacts with 1, but does not form a stable adduct at room temperature as observed by 1 H-NMR spectroscopy. The spectrum at room temperature of 1 in CDCl3 in presence of ca. five equivalents of methanol exhibits broadening of the resonances, in particular for the aromatic protons and for the signal at δ = 1.26 attributed to the methyl group pointing towards the BBN moiety, suggesting a rapid exchange process between 1 and a methanol-bound adduct. However, at lower temperature (−20 °C) signals of a new compound, corresponding to a methanol-bound adduct are present on the 1 H-NMR spectrum along with those of 1. At −40 °C, 1 is almost totally converted into a methanol-bound adduct (see SI for details). The steric repulsion between the methyl group of the methanol and the bulky surrounding of the FLP cavity is thought to disfavour the coordination of the bulkier alcohol when compared to water. The reactivity with formaldehyde was studied by placing a benzene-d6 solution of 1 at 80 °C with excess paraformaldehyde which is known to convert into formaldehyde upon heating. After 12 h, a singlet at 8.67 ppm is observed, indicative of free formaldehyde, but the resonances attributed to 1 remained unchanged. Finally, no reaction was observed when 1 was exposed to up to 80 atm of molecular hydrogen and 1 atm of carbon dioxide at 40 °C.

DFT Study of the Generated Adducts
To gain more insight on the stability of various adducts that could be generated between 1 and the molecules of interest, DFT calculations have been carried and the models are exposed in Figure 3 with the ΔG (ΔH) values given in kcal·mol −1 . First, it can be observed that the formation of adducts with CO2 or formaldehyde are quite endergonic, at 17.4 (33.1) and 15.3 (−1.1) kcal·mol −1 . The cleavage of molecular hydrogen is however more favoured, with respective values of 6.9 (−2.3) kcal·mol −1 for the formation of a zwitterionic species. The entropic contribution seems to play a very important role and explains the absence of reactivity between 1 and H2, since in terms of enthalpy the reaction should be exothermic at −2.3 kcal·mol −1 . Whereas the energy values observed for the methanol adduct justify the presence of a fluxional process (4.1 (−10.8) kcal·mol −1 ), the free energies observed for the addition of water and formic acid support the formation of novel zwitterionic compounds, with values of −1.8 (−15.3) and −3.8 (−19.1) kcal·mol −1 , respectively. Nevertheless, the ΔG values are very close to 0 kcal·mol −1 , which justify that these processes can be reversible at higher temperatures.

General Information
Unless otherwise specified, all the manipulations were conducted under an inert atmosphere of dinitrogen, using standard Schlenk and glovebox techniques. Reactions were carried either in a sealed J. Young NMR tube, in which case NMR conversions are indicated, or in standard oven dried Schlenk vessels. Benzene-d6 was purified by vacuum distillation from Na/K alloy, or by degassing by three subsequent freeze-pumpthaw cycles followed by standing over activated 3 Å molecular sieves. CDCl3 was dried by distillation over P2O5. Anhydrous CO2 was purchased from Praxair and used as received. Ultra high purity hydrogen (5.0 grade) was purchased from Praxair and used as received. 1-(2-iodophenyl)-2,2,6,6-tetramethylpiperidine and [2-(2,2,6,6-tetramethylpiperidin-1-yl)phenyl]lithium were synthesized according to literature [48,49].
NMR spectra were recorded on Agilent Technologies NMR spectrometer (Agilent Technologies, Santa Clara, CA, USA) at 500 MHz  using APPI ionization in positive mode. Products in toluene solutions were introduced to the nebulizer by direct injection. FTIR spectra were recorded using a Nicolet Magna 850 Fourier transform infrared spectrometer (Thermo Scientific, Madison, WI, USA) with a liquid nitrogen cooled narrow-band MCT detector using a diamond ATR accessory (Golden Gate, Specac Ltd, London, UK). (1). 917 mg of [2-(2,2,6,6-tetramethylpiperidin-1-yl)phenyl]lithium (4.1 mmol) were weighed into a Schlenk flask containing a Teflon coated magnetic stirring bar and dissolved in toluene (ca. 15 mL) and cooled down to ca. −80 °C using a liquid nitrogen/acetone bath. In a separate Schlenk flask, 4.1 mL (4.1 mmol) of a 1.0 M solution of BBN-Br in dichloromethane was added and the solvent was removed in vacuo to be replaced with ca. 4 mL of toluene. The solution of BBN-Br was added dropwise to the cold solution of [2-(2,2,6,6-tetramethylpiperidin-1-yl)phenyl]lithium, which was stirred vigorously throughout the addition. The resulting mixture was left to warm to r.t. and left stirring overnight. The decanted solution was filtered to a separated Schlenk flask via cannula. The resulting solution was evaporated to dryness under reduced pressure and further dried at 80 °C under vacuum for 2 h. The residue was then dissolved in hexanes (ca. 5 mL). The resulting solution was left at −35 °C for 72 h to allow complete precipitation of the title compound as a white powder (1.01 g, 73% yield). Crystals suitable for X-ray diffraction were grown by slow evaporation of a hexane solution.  (2). 2 crystallized out of a solution of 1 exposed to air from hexane and the characterisation was carried out on the few crystals obtained. However, attempts to form 2 in good yield from 1 by adding stoichiometric equivalent of water gave a mixture of 2 and another product that was identified as [2-(2,2,6,6-tetramethylpiperidin-1-yl)phenyl]boronic acid.

Conclusions
The synthesis and the structural characterization of species 1-(BBN)-2-(TMP)-C6H4 (1) was carried out. The latter molecule exhibits FLP-like reactivity and can split water, formic acid, and methanol at low temperature to generate the respective zwittterionic species, which were fully characterized. There was no reactivity observed with formaldehyde, hydrogen or carbon dioxide, therefore precluding CO2 hydrogenation. The DFT calculations involving all reagents and products that should be observed in the hydrogenation of carbon dioxide indicate that with the right tuning of the steric and electronic effects on boron and nitrogen, it would be possible to have a system where reversible formation of adducts is possible, which would make possible the catalytic reduction of carbon dioxide into methanol. We are currently investigating analogues, which should exhibit higher reactivity and enable such transformations.

Supplementary Materials
The supplementary materials include the NMR and the FT-IR spectra of compounds synthesized, the DFT data and important crystallographic parameters. Crystallographic data have been deposited with CCDC (CCDC No. 1060045 for 1 and CCDC No. 10060046 for 2). These data can be obtained upon request from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK, E-Mail: deposit@ccdc.cam.ac.uk, or via the internet at www.ccdc.cam.ac.uk. Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/20/07/11902/s1.