Synthetic strategy. The direct N-phenylation of triphenylamine (8; Fig. 3a) using a Ph cation (or its synthetic equivalent) to form Ph4N+ is difficult because 8 is weakly nucleophilic (indicated by the low pKaH value (–3.91)19 recorded during N-protonation). Ph4N+ salts could not be obtained by reacting 8 with a phenyldiazonium unit.10 The N-phenylation of 8 using diphenyliodonium20 or the in-situ-generated benzyne21 unit was also unsuccessful. We designed the triarylammoniumyl salt (9; Fig. 3b) as a novel precursor that could be used for the synthesis of Ph4N+ to address the problem of low reactivity of 8. In general, triarylamines can be oxidized to form the corresponding radical cations (referred to as triarylammoniumyls) that exhibit high reactivity. Triphenylammoniumyl easily dimerizes via the para positions of the Ph groups following the process of intermolecular radical coupling to afford tetraphenylbenzidine.22 The results obtained from quantum chemical calculations revealed that the singly occupied molecular orbital of triphenylammoniumyl was spread over all the Ph rings and the central nitrogen atom.23 Therefore, we expected that the intermolecular radical coupling reaction involving a triphenylammoniumyl unit and an aryl radical occurs via the nitrogen atom if the Ph group is hindered by steric protection. The tert-butyl and bromo groups were selected as the bulky protecting groups of 9 at the meta- and para-positions, respectively. These groups can exert a large extent of steric hindrance and can be removed at the later stages of the synthetic procedure.
Synthesis. The starting material used for the synthesis of the target was tris[(3,5-di-tert-butyl)phenyl]amine (10; Fig. 4), which was prepared over three steps starting from benzene: Friedel–Crafts reaction, dealkylative bromination, and palladium-catalyzed amination.24,25 The para-brominated compound 11 was formed in 81% yield when 10 was treated with N-bromosuccinimide (NBS). The triarylamine 11 was then activated to form the triarylammoniumyl salt 9 following the one-electron oxidation process using AgBF4.26 It was isolated as a monohydrate in 93% yield. Similar to other triarylammoniumyl salts,22 9 was a blue solid. The color could be attributed to the absorption over the visible region (lmax = 797 nm in o-dichlorobenzene). Following this, we investigated the key intermolecular radical coupling reactions. Bis(3,5-di-tert-butyl)benzoyl peroxide (13) was used as the starting material for the in situ generation of the (3,5-di-tert-butyl)phenyl radical (12). The formation of the radical proceeded via the process of O–O homolysis, which was followed by the process of decarboxylation.27 A mixture of 9 and 13 was heated to 120 ℃ in o-dichlorobenzene in the presence of (2,6-di-tert-butyl)pyridine (14; used as a base) until the characteristic blue color of 9 disappeared. The reaction conditions were selected from the results of the screening experiments (vide infra). The desired Ar4N+ salt 15 was successfully formed in a low yield (0.1%), which was then isolated using the normal-phase ion-pair chromatography technique.28 Under these conditions, 4 g of 9 could be converted to 5 mg of 15. The byproducts formed during the reaction were triarylamine 11 (11%), solvent adduct 16 (4% based on 13), and sterically congested triarylamines 17 (7%) and 18 (8%) possessing ortho-[(3,5-di-tert-butyl)benzoyl]oxy and ortho-(3,5-di-tert-butyl)phenyl groups, respectively. The structures of 17 and 18 were determined using the single-crystal X-ray diffraction technique (Supplementary Tables 2 and 3, respectively). The formation of 17 and 18 indicated that the extent of steric protection provided by the meta-tert-butyl groups in 9 was not sufficient to efficiently inhibit the occurrence of the ortho-substitution reactions at the Ph rings. Supplementary Table 4 shows the process of reaction condition screening for the intermolecular radical coupling reaction conducted on a small scale using 9 (80–100 mg). When the reaction was conducted in o-dichlorobenzene in the presence of 14 (entry 1), the yield of the desired ammonium salt 15 was 0.12% (determined by 1H-NMR spectroscopic analysis). Although the same yield (0.12%, entry 2) of 15 was obtained when the reaction was carried out in the absence of 14, it was difficult to purify the product under these conditions as various byproducts were also formed during the process. The use of other solvents in combination with 14 afforded lower (entries 3–10) or undetectable (entries 11–14) yields of 15, and a complex mixture of compounds which could not be purified or analyzed (entries 16–21). Thus, the reaction conditions presented in entry 1 were used to synthesize 15 from 9 (4 g). We also attempted the intermolecular radical coupling reaction involving 13 and tris[(3,5-di-tert-butyl)phenyl]ammoniumyl BF4− (19; devoid of the p-bromo groups). The latter was prepared following the one-electron oxidation of 10. However, the desired product tetrakis[(3,5-di-tert-butyl)phenyl]ammonium BF4− (20) could not be isolated as the reaction yielded a complex mixture. Therefore, the removal of all the bromo groups in 15 was carried out following the process of bromine–lithium exchange using nBuLi at − 78°C. The resulting product was protonated with (2,6-di-tert-butyl)pyridinium BF4− salt (21), affording 20 in 90% yield. Since we selected diacyl peroxide 13 as the precursor of aryl radical 12 to introduce the (3,5-di-tert-butyl)phenyl group in 9, the ammonium nitrogen of 20 was connected to four identical aryl groups. The counter anion of 20 was exchanged to prepare the corresponding B(C6F5)4− salt (22), the structure of which was confirmed using the single-crystal X-ray diffraction technique (Supplementary Table 5). The final step toward the formation of Ph4N+ involved the dealkylation of the tert-butyl groups present on the aromatic rings of 20. All the eight tert-butyl groups could be successfully removed when 20 was heated at 150 ℃ over a period of 14 h in a solvent amount of trifluoromethanesulfonic acid (TfOH).29 The reaction afforded Ph4N+ BF4− (23) in 59% yield. This result indicates the high stability of Ph4N+ under extremely harsh acidic conditions. Following the process of counter anion exchange, the BF4− salt (23) was converted to the B(C6F5)4− salt (24; yield: 81%; white solid). The purity of the counter anion was confirmed using the 19F-NMR spectroscopy technique.
1 H- and 13C-NMR spectra. The 1H-NMR signals corresponding to 24 (spectra recorded in (CD3)2CO) appeared at approximately 7.89, 7.69, and 7.65 ppm. The signal corresponded to the ortho, meta, and para-protons present in the Ph ring, respectively. The 13C-NMR signals corresponding to 24 (spectra recorded in (CD3)2CO) appeared at 149.7 (ipso), in the range of 131.4–131.2 (para and meta), and at 126.8 (ortho) ppm. The signals were assigned to the corresponding carbon atoms using the HMQC technique. The 1H and 13C-NMR signals corresponding to 24 appeared downfield compared to the signals corresponding to 8 (Figs. 5a,b). The downfield shift can be attributed to the strong inductive effect exerted by the ammonium nitrogen in 24 and the loss of the resonance effect of the lone pair of electrons on nitrogen present in 8 following N-quaternization. The signals corresponding to the meta and para protons present in 24 (at ~ 7.69 and ~ 7.65 ppm, respectively) appeared at up-field compared to the signals corresponding to Ph4P+ B(C6F5)4−30 (25; ~7.88 and ~ 8.02 ppm for meta and para protons, respectively). The up-field shift may be attributed to the strong anisotropic effects observed in Ph4N+. The generation of the strong anisotropic effects can be attributed to the fact that Ph4N+ is smaller than Ph4P+. Similarly, we observed that the signals corresponding to the meta and para protons in Ph4C ((CD3)2CO; at ~ 7.29 and ~ 7.21 ppm, respectively) appeared up-field compared to the signals corresponding to Ph4Si (meta and para protons appear at ~ 7.44 and ~ 7.48 ppm, respectively; Supplementary Fig. 1).31
Single-crystal X-ray structure analysis. The single-crystal X-ray diffraction technique was used to analyze the structure of 24. Analysis of the results proved the quaternary ammonium structure of 24 (Fig. 5c, top view). The counter anion B(C6F5)4− was omitted for clarity (Supplementary Table 6). The Ph4N+ structure exhibited S4-like symmetry and not D2d-like symmetry. The result agreed well with the theoretically predicted result.32 The N–C(sp2) bond length in 24 (present between the Ph4N+ nitrogen unit and the sp2 carbon atom) in the Ph group was 1.529 ± 0.003 Å (Fig. 5c, side view). This bond is longer than the N–C(sp2) bonds in (CH3)3PhN+, (CH3)2Ph2N+, (CH3)Ph3N+, and N,N-diphenylcarbazolium, which were 1.50,33 1.51,21 1.52,21 and 1.51–1.5216 Å, respectively (data from Cambridge Crystallographic Data Center (CCDC) deposition numbers of 291166, 1433867, 1433868, and 1890475, respectively). The long N–C(sp2) bond in Ph4N+ indicates the presence of an unusually hindered environment around the ammonium nitrogen atom. The lengths of the bonds formed between the central atom and the sp2 carbons in Ph4C, Ph4B−, Ph4P+, Ph4Si, and Ph4Al− were 1.56,34 1.64–1.66,35 1.79,36 1.88,37 and 2.00–2.0338 Å, respectively. Thus, Ph4N+ is characterized by the most sterically congested environment among these Ph4Z0 ± 1, reflecting the difficulty faced during synthesis. The shortest distance between the ortho-hydrogen in the Ph unit and the ipso carbon in the adjacent Ph group in Ph4N+ was 2.46 Å (Fig. 5c, side view). The Van der Waals radii for hydrogen (1.00 Å) and carbon (1.77 Å) indicate that steric repulsion is generated.39 The corresponding H–C distances in Ph4C, Ph4B−, and Ph4P+ were 2.54,34 2.59,35 and 2.7636 Å, respectively, indicating that the extent of steric repulsion observed in these cases was lower than that observed in Ph4N+. The N–C(sp2) bond length in 22 was in the range of 1.53–1.54 Å and the H–C distance was 2.48 Å. These values are slightly higher than the corresponding values recorded for 24. This suggested the generation of steric and electronic effects in the presence of the meta-tert-butyl groups in 22 present in the ammonium structure.