Chloro(η²,η²-cycloocta-1,5-diene){1-benzyl-3-[(S)-2-hydroxy-1-methylethyl]benzimidazol-2-ylidene}rhodium(I)

Abstract

Previously, we demonstrated the synthesis of a well-defined hydroxyalkyl-functionalized N-heterocyclic carbene (NHC)/Ru(II) complex through the transmetalation reaction between [RuCl₂(p-cymene)]₂ and the corresponding NHC/Ag(I) complex derived from a chiral benzimidazolium salt using the Ag₂O method. In this study, we successfully synthesized [RhX(cod)(NHC)] complexes through a one-pot deprotonation route. The hydroxyalkyl-substituted benzimidazolium salt reacted with [Rh(OH)(cod)]₂ in THF at room temperature, affording the corresponding monodentate NHC/Rh(I) complex in nearly quantitative yield. The rhodium complex was characterized using NMR, HRMS measurement, and elemental analysis.

1. Introduction

Recently, there has been considerable interest in the transition metal complex having an N-heterocyclic carbene (NHC) ligand with hydroxyalkyl sidearms, owing to the numerous expected applications of complexes incorporating chiral NHC ligands in asymmetric catalysis [1,2,3,4,5]. Scheme 1 showcases representative monodentate NHC/metal complexes, the structural formulas of which have been elucidated through various analyses. In 2014, a [PdCl₂(NHC)] complex was synthesized by reacting an imidazolinium salt bearing a hydroxyalkyl sidearm with PdCl₂ in the presence of KO^tBu [6]. Additionally, Grisi and coworkers synthesized a [PdCl₂(NHC)(MeCN)] complex through transmetalation from the corresponding bis(NHC)/Ag complex [7]. Structural characterization of the NHC/Pd complex was performed using X-ray diffraction studies. Fiksdahl and coworkers reported the synthesis of an [AuCl(NHC)] complex by allowing a hydroxyalkyl-substituted imidazolinium salt derived from (S)-2-phenylglycinol to react with [AuCl(Me₂S)] in the presence of K₂CO₃ [8]. Furthermore, several research groups have successfully synthesized well-defined anionic alkoxide–NHC/metal (Cu, Ag, Ni, and Pd) complexes [9,10,11].

Previously, we showed a highly enantioselective allylic alkylation reaction catalyzed by copper species bearing a chiral hydroxyalkyl-functionalized NHC ligand derived from naturally occurring α-amino acids [12]. During this investigation, we successfully synthesized a novel [RuCl₂(NHC)(p-cymene)] complex from the hydroxyalkyl-substituted benzimidazolium salt using the Ag₂O method (Scheme 1). The monodentate NHC/Ru(II) complex was obtained utilizing the following experimental procedure: specifically, an azolium salt derived from (S)-valinol was reacted with Ag₂O at room temperature for 2 h. Subsequently, [RuCl₂(p-cymene)]₂ was introduced into the reaction vessel. After stirring the resultant reaction mixture at room temperature for 16 h, the corresponding [RuCl₂(NHC)(p-cymene)] complex was obtained in a 62% yield (Scheme 1). Here, we present the synthesis and characterization of an NHC/Rh(I) complex featuring a hydroxyalkyl-functionalized NHC ligand. The desired [RhX(cod)(NHC)] complexes were synthesized via a one-pot deprotonation route by reacting benzimidazolium salt with [Rh(OH)(cod)]₂.

2. Results and Discussion

Hydroxyalkyl-functionalized benzimidazolium salts were synthesized from commercially available chiral β-amino alcohols using Ishida and Saigo’s synthetic route (Scheme 2) [13]. The synthesis started with a nucleophilic substitution reaction between 2-fluoronitrobenzene and (S)-alaninol, yielding (S)-2-[N-(2-nitrophenyl)amino]propan-1-ol. Subsequent reduction of the nitro compound produced 2-[N-(2-aminophenyl)amino]propan-1-ol. Then, the condensation reaction between the resulting diamino compound and triethyl orthoformate afforded 2-(benzimidazol-1-yl)propan-1-ol. Finally, coupling the azole with an alkyl halide (R-X) produced the corresponding hydroxyalkyl-substituted benzimidazolium salt. In this study, we synthesized two azolium salts, 1a and 2a, derived from benzyl chloride and benzhydryl bromide, respectively. Further details are provided in Section 3.

In previous investigations, the synthesis of NHC/metal (Pd, Au, and Ru) complexes involved treating a hydroxyalkyl-substituted azolium salt with appropriate bases such as KO^tBu, K₂CO₃, and Ag₂O, as outlined in the introductory section (Section 1). In this study, we showed a synthetic approach for the NHC/Rh complex using the following one-pot deprotonation route: treatment of azolium salt 1a with [Rh(OH)(cod)]₂ in THF at room temperature afforded monodentate [RhCl(cod)(NHC)] complex 1b in nearly quantitative yield (Scheme 3). Complex 1b, isolated as an air-stable yellow solid, was characterized by analyzing the acquired analytical and spectroscopic data (further details are provided in Section 3). In the HRMS (ESI-TOF) measurement, the [M−Cl]⁺ ion (M = C₂₅H₃₀ClN₂ORh) was clearly observed. In the ¹³C{¹H} NMR spectrum, a doublet signal at δ = 196.3 ppm with a typical C–Rh coupling constant of 50.8 Hz was observed for the carbene carbon atom. Complex 1b was found to exist as a 75:25 mixture of two NHC/Rh complexes. Enders et al. observed the hindered rotation of the carbene-metal bond in an NHC/Rh complex, which contained a bulky cyclooctadiene ligand [14]. The four doublet signals at δ = 100.7 ppm (J = 6.7 Hz), 99.9 ppm (J = 6.7 Hz), 70.0 ppm (J = 14.4 Hz), and 68.5 ppm (J = 14.4 Hz) were attributed to the four non-equivalent sp² carbons of the cod ligand on complex 1b in the ¹³C{1H} NMR spectrum. Additionally, four singlet signals for the sp³ carbons of cod at δ = 33.8, 31.5, 29.5, and 27.6 ppm were observed. In the ¹H NMR spectrum, the doublet signal assigned to the methyl group adjacent to the chiral carbon center of 1b appeared at δ = 1.78 ppm with a coupling constant of 7.6 Hz. Furthermore, the hydroxy group at the NHC sidearm was observed at δ = 3.27 ppm. This strongly suggests that [RhCl(cod)(NHC)] complex 1b possesses an N-hydroxyalkyl functional group, indicating that an anionic alkoxide-tethered NHC/Rh(I) complex is not formed under these reaction conditions.

Similarly, [RhBr(cod)(NHC)] complex 2b was synthesized by reacting 2a featuring an N-CHPh₂ wingtip with [Rh(OH)(cod)]₂ in THF. Notably, following the reaction, a substantial amount of yellow precipitate formed. Subsequent simple filtration and washing with ether yielded the desired NHC/Rh(I) complex 2b in its pure form. This differs from the preparation of complex 1b. ¹H NMR, HRMS measurements, and elemental analysis strongly supported the chemical structure of 2b (details are provided in Section 3). However, attempts to measure ¹³C{¹H} NMR in CDCl₃, (CD₃)₂SO, CD₃OD, or (CD₃)₂CO failed owing to the poor solubility of 2b.

3. Materials and Methods

All reagents, including [Rh(OH)(cod)]₂ and solvents were purchased from chemical suppliers and utilized without additional purification. ¹H (400 MHz) and ¹³C{1H} (100 MHz) NMR spectra were acquired on a JEOL ECS-400 spectrometer (JEOL, Tokyo, Japan). Chemical shifts are reported downfield from TMS (δ = 0 ppm) for ¹H NMR. For ¹³C{¹H} NMR, chemical shifts are reported relative to CDCl₃ as an internal reference. High-resolution mass spectrometry was conducted on a Bruker microTOF II instrument (Bruker Daltonik Gmbh, Bremen, Germany) employing electrospray ionization (ESI). Elemental analyses were carried out at Osaka University. An azolium salt, specifically 1-benzyl-3-[(S)-2-hydroxy-1-methylethyl]benzimidazolium bromide (1a), was synthesized following our previously reported procedure [12].

3.1. Chloro(η²,η²-cycloocta-1,5-diene){1-benzyl-3-[(S)-2-hydroxy-1-methylethyl]-benzimidazol-2-ylidene}rhodium(I) (1b)

1-Benzyl-3-[(S)-2-hydroxy-1-methylethyl]-benzimidazolium chloride (1a) (0.21 mmol, 64 mg) and [Rh(OH)(cod)]₂ (0.1 mmol, 46 mg) were stirred in THF (2 mL) at room temperature for 16 h under Ar. After passing through a short silica gel column using THF as a solvent, the filtrate was evaporated using a rotary evaporator, yielding [RhCl(cod)(NHC)] complex 1b as a yellow solid (103 mg, 99% yield): ¹H NMR (400 MHz, CDCl₃): Major isomer: δ = 7.47 (d, J = 8.8 Hz, 1H), 7.34–7.27 (m, 5H), 7.14 (td, J = 0.8 and 10.0 Hz, 1H), 7.05 (t, J = 7.6 Hz, 1H), 6.98 (d, J = 8.0 Hz, 1H), 6.63–6.54 (m, 1H, CH₂OH), 6.33 (d, J = 15.6 Hz, 1H, CH₂Ph), 6.03 (d, J = 15.6 Hz, 1H, CH₂Ph), 5.18–5.16 (m, 1H, CH_cod), 5.12–5.07 (m, 1H, CH₂OH), 4.22–4.12 (m, 1H, CHN), 4.11–4.09 (m, 1H, CH_cod), 3.68–3.65 (m, 1H, CH_cod), 3.52–3.26 (m, 1H, CH_cod), 3.27–3.26 (m, 1H, OH), 2.59–2.43 (m, 2H, CH_2cod), 2.37–2.28 (m, 1H, CH_2cod), 2.19–2.06 (m, 3H, CH_2cod), 1.92–1.83 (m, 2H, CH_2cod), 1.78 (d, J = 7.6 Hz, 3H, CH₃) ppm. Minor isomer: δ = 7.39 (d, J = 8.8 Hz, 1H), 7.18–7.12 (m, 1H), 6.93 (d, J = 8.0 Hz, 1H), 6.48 (d, J = 15.6 Hz, 1H, CH₂Ph), 6.37 (d, J = 15.6 Hz, 1H, CH₂Ph), 4.08–4.06 (m, 1H, CH_cod), 3.57 (br, 1H, CH_cod), 1.66 (d, J = 7.6 Hz, 3H, CH₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): Major isomer: δ = 196.3 (d, J_C-Rh = 50.8 Hz, C_carbene), 135.6, 135.5, 128.7, 127.7, 126.9, 122.3, 122.3, 111.4 (C of of NHC ring), 111.3 (C of of NHC ring), 100.7 (d, J_C-Rh = 6.7 Hz, CH_cod), 99.9 (d, J_C-Rh = 6.7 Hz, CH_cod), 70.0 (d, J_C-Rh = 14.4 Hz, CH_cod), 68.5 (d, J_C-Rh = 14.4 Hz, CH_cod), 63.7 (NCH), 59.4 (CH₂O), 52.5 (CH₂Ph), 33.8 (CH_2cod), 31.5 (CH_2cod), 29.5 (CH_2cod), 27.6 (CH_2cod), 16.3 (CH₃) ppm. Minor isomer: δ = 196.4 (d, J_C-Rh = 50.8 Hz, C_carbene), 135.9, 134.7, 128.7, 127.6, 126.8, 122.4, 111.1 (C of the NHC ring), 99.3 (d, J_C-Rh = 6.7 Hz, CH_cod), 98.5 (d, J_C-Rh = 6.7 Hz, CH_cod), 63.8 (NCH), 58.4 (CH₂O), 32.9 (CH_2cod), 30.7 (CH_2cod), 28.9 (CH_2cod), 27.9 (CH_2cod), 17.0 (CH₃) ppm. HRMS (ESI-TOF), m/z: calculated for C₂₅H₃₀N₂ORh [M-Cl]⁺, 477.1408, found, 477.1385. The NMR spectrum can be found in the Supplementary Materials.

3.2. 1-[(S)-2-hydroxy-1-methylethyl]-3-(diphenylmethyl)benzimidazolium Bromide (2a)

A mixture of (S)-2-benzimidazol-1-yl-propan-1-ol (4.2 mmol, 740 mg) and benzhydryl bromide (4.0 mmol, 989 mg) in toluene (18 mL) was stirred at 110 °C for 72 h. The solvent was evaporated under reduced pressure upon completion of the reaction, resulting in a brown liquid. The product obtained from the residue was isolated via column chromatography on silica gel (CH₂Cl₂/CH₃OH = 95/5). The desired azolium salt 2a was further purified by reprecipitating in CHCl₃ and CH₃CO₂C₂H₅, yielding a white solid (620 mg, 37% yield): ¹H NMR (400 MHz, CDCl₃): δ = 9.86 (s, 1H, NCHN⁺), 7.93 (d, J = 8.5 Hz, 1H), 7.55 (t, J = 7.9 Hz, 1H), 7.48–7.38 (m, 12H), 7.24 (d, J = 8.5 Hz, 1H), 5.20–5.16 (m, 1H, CH₂O), 5.09 (t, J = 6.5 Hz, 1H, OH), 4.05–3.95 (m, 2H, NCH and CH₂O), 1.64 (d, J = 6.7 Hz, 3H, CH₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 140.9 (NCHN⁺), 135.2, 131.9, 131.3, 129.5, 129.4, 129.4, 129.3, 128.6, 128.4, 127.0, 126.9, 114.9 (C of azolium), 114.3 (C of azolium), 66.5 (NCH), 62.9 (OCH₂), 57.4 (NCH₂), 16.7 (CH₃) ppm. Elemental analysis calculated (%) for C₂₃H₂₃BrN₂O: C 65.25, H 5.48, N 6.62; found: C 65.15, H 5.44, N 6.56. The NMR spectrum can be found in the Supplementary Materials.

3.3. Bromo(η²,η²-cycloocta-1,5-diene){1-[(S)-2-hydroxy-1-methylethyl]-3-diphenylmethylbenzimidazol-2-ylidene}rhodium(I) (2b)

Azolium bromide 2a (0.137 mmol, 58 mg) and [Rh(OH)(cod)]₂ (0.065 mmol, 30 mg) were stirred in THF (2 mL) at room temperature for 16 h under Ar. After the reaction, a yellow precipitate formed. The resulting yellow solid was collected by filtration and washed with ether. The desired [RhBr(cod)(NHC)] complex 2b was obtained as a yellow solid (58 mg, 70% yield): ¹H NMR (400 MHz, CDCl₃): Major isomer: δ = 8.75 (s, 1H, Ph₂CH), 7.47 (d, J = 8.2 Hz, 1H), 7.41–7.39 (m, 5H), 7.37–7.35 (m, 2H), 7.25–7.23 (m, 3H), 7.09 (t, J = 7.7 Hz, 1H), 6.89 (t, J = 7.9 Hz, 1H), 6.74 (d, J = 8.2 Hz, 1H), 6.56–6.50 (m, 1H, CH₂OH), 5.31 (br, 1H, CH_cod), 5.12–5.09 (m, 1H, CH₂OH), 4.27–4.19 (m, 1H, CHN), 4.15–4.10 (m, 1H, CH_cod), 3.50 (br, 1H, CH_cod), 3.27 (dd, J = 2.9 and 9.3 Hz, 1H, OH), 2.78 (br, 1H, CH_cod), 2.54–2.42 (m, 2H, CH_2cod), 2.23–2.15 (m, 1H, CH_2cod), 2.09 (br, 1H, CH_2cod), 1.99 (br, 1H, CH_2cod), 1.85–1.64 (m, 2H, CH_2cod), 1.44–1.43 (m, 1H, CH_2cod), 1.78 (d, J = 7.2 Hz, 3H, CH₃) ppm. Minor isomer: δ = 3.74 (br, 1H, CH_cod), 2.15 (br, 1H, CH_2cod), 1.73 (d, J = 7.2 Hz, 3H, CH₃) ppm. Elemental analysis calculated (%) for C₃₁H₃₄BrN₂ORh▪H₂O: C 57.16, H 5.57, N 4.30; found: C 57.54, H 5.31, N 4.45. HRMS (ESI-TOF), m/z: calculated for C₃₁H₃₄N₂Rh [M-Br]⁺, 553.1721, found, 553.1723. The NMR spectrum can be found in the Supplementary Materials.

4. Conclusions

In summary, two rhodium complexes featuring hydroxyalkyl-functionalized NHC ligands were successfully synthesized by treating the corresponding benzimidazolium salts with [Rh(OH)(cod)]₂ via a one-pot deprotonation route. This is a new addition to hydroxyalkyl-functionalized NHC/metal complexes. Further investigations are underway to explore the preparation of conformationally stable anionic alkoxide–NHC/metal complexes and their potential applications in enantioselective transformation reactions.