Asymmetric Synthesis of Enantiomerically Pure Mono- and Binuclear

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Asymmetric Synthesis of Enantiomerically Pure Mono- and Binuclear Bis(cyclometalated) Iridium(III) Complexes Su-Yang Yao, Yan-Ling Ou, and Bao-Hui Ye* †

MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China S Supporting Information *

ABSTRACT: Chiral precursors Λ-[Ir(ppy)2(L-pro)] (Λ-L, where ppy is 2-phenylpyridine; pro is proline), Λ-[Ir(ppy)2(MeCN)2](PF6) (Λ-1), Δ-[Ir(ppy)2(D-pro)] (Δ-D), and Δ[Ir(ppy)2(MeCN)2](PF6) (Δ-1) were synthesized from rac[(Ir(ppy)2)2Cl2] and L-pro or D-pro by means of the auxiliary ligand strategy with 99% de values. The enantiopure mono complexes Λ/Δ-[Ir(ppy)2(L)](PF6) (L is 2,2′-bipyridine, Λ/ Δ-2; L is 2,2′-dipyrimidine (dpm), Λ/Δ-3; L is 2,2′bibenzimidazole (H2bbim), Λ/Δ-4) with 99% ee values and binuclear complexes ΛΛ/ΔΔ-[(Ir(ppy) 2 ) 2 (dpm)](PF 6 ) 2 (ΛΛ-5 and ΔΔ-5) and ΛΛ/ΔΔ-[(Ir(ppy)2)2(bbim)] (ΛΛ-6 and ΔΔ-6) with 99% de values were synthesized in one step using the corresponding chiral precursors. The absolute configurations at Ir(III) centers of precursor Δ-1, mononuclear Λ-3, and binuclear ΔΔ-6 were confirmed by single-crystal structural analysis and characterized by circular dichroism (CD) spectroscopy. The correlation between the absolute configuration at Ir(III) center and CD spectra was established. The configurations at Ir(III) centers are stable during the reactions, and the chiral precursors can be used for the asymmetric synthesis of enantiomerically pure mono- and polynuclear Ir(III) complexes. Moreover, meso ΛΔ-[(Ir(ppy)2)2(dpm)](PF6)2 (meso-5) and ΛΔ[(Ir(ppy)2)2(bbim)] (meso-6) were also synthesized using these precursors.

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INTRODUCTION Ir(III)-bis(phenylpyridine) (Ir(ppy)2) complexes have received growing attention over many years because of their excellent photophysical properties.1 The enantiomerically pure octahedral Ir(III) complexes have been widely employed as luminescence probes for nucleic acid,2 enzyme inhibitors,3 emitters of circularly polarized luminescence,4 and threedimensional electronic displays5 as well as in asymmetric synthesis.6 Though mononuclear enantiomerically cyclometalated Ir(III) complexes have been well-documented, the synthesis of binuclear and polynuclear Ir(III) complexes has been less explored.4b Resolution of the racemic Ir(ppy)2 complexes into Δ and Λ enantiomers has been achieved by the chromatographic methods with a chiral stationary phase4a,7 or using optically pure tris(tetrachlorobenzenediolato)phosphate(V) (Δ-TRISPHAT) anion as a mobile phase.8 Moreover, diastereoselective synthesis was also employed to prepare Ir(III) complexes via the introduction of a chiral ligand.9 Recently, asymmetric synthesis of optically pure cyclometalated Ir(III) complexes via a chiral auxiliary ligand, such as amino acid, phenol-oxazoline, or phenol-thiazolines, have been developed and successfully applied to the preparation of mononuclear complexes.6,10,11 However, a column chromatography technique usually needed to be used to separate the diastereomers in these processes, and sometimes, only partial resolution was achieved.10a−c There© XXXX American Chemical Society

fore, it is still highly desirable to exploit effective methods to synthesize chiral cyclometalated Ir(III) complexes, in particular, for the binuclear and polynuclear Ir(III) complexes.4b,10a Recently, we reported an approach for “coordination oxidation in situ” to asymmetrically synthesize sulfoxides via chiral-at-metal of Ru(II) complexes.12 Inspired by the excellent precursor of Δ/Λ-[Ru(bpy)2(py)2]2+ (bpy is 2,2′-bipyridine) developed by Zelewsky’s group,13 which has been widely used in the synthesis of chiral Ru(II) complexes, our aim is to develop enantiomerically pure precursors like Δ/Λ-[Ru(bpy)2(py)2]2+, which have high reactivity and can be used in asymmetric synthesis of mononuclear and polynuclear Ir(III) complexes with chiral-at-metal only. The commercial available amino acids D/L-serine (ser)10a and proline (pro)10e,14 were successfully used as chiral auxiliary ligands to synthesize chiral Ir(III) and Ru(II) complexes. Herein the enantiomerically pure precursors Λ-[Ir(ppy)2(L-pro)] (Λ-L) and Δ-[Ir(ppy)2(D-pro)] (Δ-D) were synthesized. The chiral precursors can be used in the asymmetric synthesis of mononuclear and polynuclear enantiopure Ir(ppy)2 complexes by replacement of the auxiliary ligand. In addition, the more universal and active precursors Λ[Ir(ppy)2(MeCN)2](PF6) (Λ-1) and Δ-[Ir(ppy)2(MeCN)2](PF6) (Δ-1) were also developed, which can be used in the Received: March 2, 2016

A

DOI: 10.1021/acs.inorgchem.6b00527 Inorg. Chem. XXXX, XXX, XXX−XXX

Article

Inorganic Chemistry

2H), 1.97 (s, 6H). 13C NMR (151 MHz, CD3CN) δ 166.93, 150.97, 144.59, 143.69, 138.94, 131.11, 129.53, 124.17, 123.57, 122.61, 119.65, 119.43, 54.30. ESI-MS: m/z = 582.9 [M−PF6]+. Crystals of Δ-1 were obtained by slow evaporation of a DCM solution of Δ-1. CD for Δ-1 (Δε, M−1 cm−1, DCM): 257 (−54), 301 (20), 328 (−26), 424 nm (5). CD for Λ-1 (Δε, M−1 cm−1, DCM): 258 (50), 303 (−32), 328 (40), 423 nm (−9). Syntheses of Enentiomerically Pure Mononuclear Ir(III) Complexes. Synthesis of Λ-[Ir(ppy) 2 (bpy)](PF 6 ) and Δ-[Ir(ppy)2(bpy)](PF6). Method A: Λ-1 or Δ-1 (25.0 mg, 0.0344 mmol) and bpy (7.9 mg, 0.0513 mmol) were dissolved in 5 mL of DCM; then, the solution was stirred under N2 atmosphere at room temperature for 1 h. The solvent was removed, and the product was purified by recrystallization from DCM−Et2O. Yield, 24.0 mg, 87%. Method B: Λ-L or Δ-D (20.0 mg, 0.0326 mmol) and bpy (7.6 mg, 0.0493 mmol) were dissolved in DCM (4 mL) under N2 atmosphere at room temperature; then, TFA (7.5 μL, 0.1013 mmol) was added. The solution was stirred for another 1 h and then washed with saturated KPF6 solution (3 × 15 mL). The organic phase was dried over Na2SO4, filtered, and concentrated. The product was purified by recrystallization from DCM−Et2O. Yield, 33.0 mg, 88%. Anal. Calcd for C32H24IrN4PF6: C 47.94, H 3.02, N 6.99; Found: C 47.74; H 2.85, N 6.84%. 1H NMR (400 MHz, CDCl3) δ 8.71 (d, J = 8.2 Hz, 2H), 8.17 (t, J = 7.9 Hz, 2H), 8.01−7.89 (m, 4H), 7.79 (t, J = 7.8 Hz, 2H), 7.71 (d, J = 7.8 Hz, 2H), 7.53 (d, J = 5.8 Hz, 2H), 7.46−7.41 (m, 2H), 7.09−7.03 (m, 4H), 6.95 (t, J = 7.4 Hz, 2H), 6.32 (d, J = 7.6 Hz, 2H). ESI-MS: m/z = 656.9 [M−PF6]+. CD for Δ-2 (Δε, M−1 cm−1, DCM): 262 (−55), 286 (+97), 321 (−39), 436 nm (+7). CD for Λ-2 (Δε, M−1 cm−1, DCM): 262 (+56), 286 (−101), 320 (+38), 434 nm (−8). Synthesis of Λ-[Ir(ppy)2(dpm)](PF6) and Δ-[Ir(ppy)2(dmp)](PF6). Method A: Λ-1 or Δ-1 (21.0 mg, 0.0289 mmol) and 2,2′-dipyrimidine (dpm, 6.8 mg, 0.0434 mmol) were dissolved in 5 mL of DCM; then, the solution was stirred under N2 atmosphere at room temperature for 20 min. The DCM solvent was removed under reduced pressure. The crude product was purified on a silica-gel flash column chromatography (DCM/MeOH 100:0.3 as an eluent). Yield, 19.0 mg, 83%. Anal. Calcd for C30H22IrN6PF6: C 44.83, H 2.76, N 10.46; Found: C 44.73; H 2.64, N 10.23%. 1H NMR (300 MHz, CDCl3) δ 9.21 (dd, J = 4.8, 2.2 Hz, 2H), 8.23 (dd, J = 5.5, 2.2 Hz, 2H), 7.95 (d, J = 7.9 Hz, 2H), 7.81 (td, J = 7.9, 1.5 Hz, 2H), 7.74−7.65 (m, 6H), 7.15 (ddd, J = 7.3, 5.9, 1.4 Hz, 2H), 7.06 (td, J = 7.6, 1.2 Hz, 2H), 6.95 (td, J = 7.4, 1.3 Hz, 2H), 6.30 (dd, J = 7.6, 0.9 Hz, 2H). 13C NMR (151 MHz, CDCl3) δ 167.33, 161.98, 159.80, 157.27, 149.23, 147.21, 143.31, 138.70, 131.79, 131.13, 125.55, 124.95, 124.03, 123.36, 119.83. ESI-MS: m/z = 659.0 [M−PF6]+. CD for Δ-3 (Δε, M−1 cm−1, DCM): 259 (−63), 283 (+14), 306 (+22), 332 (−28), 431 nm (12). CD for Λ-3 (Δε, M−1 cm−1, DCM): 259 (+79), 283 (−16), 306 (−28), 332 (+35), 432 nm (−16). Method B: Δ-D or Λ-L (30.0 mg, 0.0489 mmol) and dpm (12.0 mg, 0.0759 mmol) were dissolved in 6 mL of DCM under N2 atmosphere at room temperature; then, TFA (11 μL, 0.1486 mmol) was added. The solution was stirred for 1 h and then washed with saturated KPF6 solution (3 × 15 mL). The organic phase was dried over Na2SO4, filtered, and concentrated to dryness. The products were purified by crystallization from DCM−toluene. Yield, 34.0 mg, 87%. Crystals of Λ-3 were obtained by diffusing Et2O into a DCM solution of Λ-3. Synthesis of Λ-[Ir(ppy)2(H2bbim)](PF6) and Δ-[Ir(ppy)2(H2bbim)](PF6). Author: Method A: Λ-1 or Δ-1 (20.0 mg, 0.0275 mmol) and 2,2′-bibenzimidazole (H2bbim, 7.7 mg, 0.0329 mmol) were added to 5 mL of 1,2-dichloroethane (DCE) solution. The solution was stirred at 60 °C under N2 atmosphere for 2 h. After it cooled to room temperature, the solution was concentrated, and the crude material was purified via silica gel chromatography (DCM/MeOH = 100:0.5 to DCM/MeOH = 100:1 as eluents). Yield, 15.8 mg, 78%. Method B: ΛL or Δ-D (15.0 mg, 0.0244 mmol) and H2bbim (8.6 mg, 0.0366 mmol) were dissolved in 4 mL of DCE solution under N2 atmosphere at room temperature; then, to this TFA (5.4 μL, 0.0735 mmol) was added. The solution was stirred for 1.5 h and then was washed with saturated KPF6 solution (3 × 15 mL). The organic phase was collected and concentrated. The crude material was purified by a silica gel

asymmetric syntheses of enantiomerically pure homochiral and heterochiral binuclear Ir(ppy)2 complexes.

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EXPERIMENTAL SECTION

Materials and Methods. The chemicals were purchased from chemical company. rac-[(Ir(ppy)2Cl)2] was prepared according to the reference.15 All reactions were performed under a N2 atmosphere and in the dark. Column chromatography was performed with silica gel (300−400 mesh). Elemental (C, H, and N) analyses were performed on an Elementar Vario EL analyzer. Thermogravimetric (TG) analyses were performed on a Netzsch TG 209 instrument in following N2 with a heating rate of 10 °C/min. Electrospray ionization mass spectra (ESI-MS) were obtained on a Thermo LCQ DECA XP mass spectrometer. NMR spectra were recorded with a Varian Mercury-Plus 300, Bruker AV 400, or Bruker AV 600 spectrometer by using the solvent as an internal standard. Circular dichroism (CD) spectra were measured on a JASCO J-810 CD spectro-polarimeter (1 s response, 3.41 nm bandwidth, scanning speed of 200 nm/min, accumulation of three scans). The diastereomeric ratio (dr) values of Δ-D and Λ-L were determined by 1H NMR spectra. The ee values of mononuclear complexes were measured by Chiral HPLC chromatograms analyses on a Shimadzu LC 20AT with UV detector SPD-20A (Daicel Chiralpak AD-H column, 250 mm × 4.6 mm, flow rate: 1 mL/min, column temperature 35 °C, 300 nm). Emission spectra and lifetimes were performed on a FLS920 fluorescence lifetime and steady-state spectrometer. Syntheses of Chiral Precursors. Synthesis of Λ-[Ir(ppy)2(L-pro)] and Δ-[Ir(ppy)2(D-pro)]. A mixture of rac-[(Ir(ppy)2Cl)2] (157.8 mg, 0.147 mmol), L-pro or D-pro (50.7 mg, 0.441 mmol), and NaOMe (31.7 mg, 0.588 mmol) was added to a MeOH (15 mL) solution. The solution was stirred under N2 atmosphere at 50 °C for 24 h. The solvent was removed, and the resulting material was dissolved in 30 mL of dichloromethane (DCM) and then washed with H2O (3 × 10 mL) to remove the unreacted pro. The combined organic extract was dried over Na2SO4, filtered, and concentrated under high vacuum. The product was washed with CHCl3 (2 × 15 mL) to give a yellow solid with strong luminescence. Yield, 54.0 mg, 35%. The dr value is found to be 100:1 (determined by 1H NMR spectra integral). Anal. Calcd for C27H24IrN3O2: C 52.84, H 3.78, N 6.85; Found: C 52.53; H 3.62, N 6.54%. 1H NMR (300 MHz, deuterated dimethyl sulfoxide (DMSOd6)) δ 9.03 (d, J = 5.5 Hz, 1H), 8.66 (d, J = 4.7 Hz, 1H), 8.16 (t, J = 7.6 Hz, 2H), 7.95 (t, J = 7.7 Hz, 2H), 7.71 (dd, J = 10.1, 8.2 Hz, 2H), 7.47 (t, J = 6.7 Hz, 1H), 7.41 (t, J = 6.5 Hz, 1H), 6.76 (t, J = 7.4 Hz, 2H), 6.63 (t, J = 5.8 Hz, 1H), 6.58 (t, J = 5.3 Hz, 1H), 6.30 (d, J = 7.1 Hz, 1H), 5.88 (d, J = 7.4 Hz, 2H), 3.79 (dd, J = 14.5, 8.6 Hz, 1H), 2.24−2.10 (m, 1H), 2.05−1.90 (m, 1H), 1.78 (td, J = 13.9, 7.0 Hz, 1H), 1.61−1.48 (m, 1H), 1.45−1.28 (m, 2H). 13C NMR (151 MHz, DMSO-d6) δ 182.89, 169.06, 168.18, 152.81, 150.41, 148.18, 148.06, 145.10, 144.62, 138.39, 138.18, 133.00, 132.26, 129.28, 129.08, 124.84, 124.50, 123.23, 123.04, 120.96, 120.38, 119.64, 119.54, 61.79, 48.18, 30.94, 26.36. CD for Λ-L (Δε, M−1 cm−1, DCM): 264 (46), 284 (−13), 318 (+25), 382 (+17), 418 (+6), 500 nm (−8). CD for Δ-D (Δε, M−1 cm−1, DCM): 264 (−38), 287 (+9), 317 (−21), 381 (−15), 418 (−5), 499 nm (+7). Synthesis of Λ-[Ir(ppy)2(MeCN)2](PF6) and Δ-[Ir(ppy)2(MeCN)2](PF6). A suspension of Λ-L or Δ-D (30.0 mg, 0.489 mmol) in MeCN (5 mL) was stirred and degassed with N2 at room temperature for 5 min, then trifluoroacetic acid (TFA; 9 μL, 0.122 mmol) was added. The solution became clear and turned pale yellow. The solution was stirred at room temperature for another 1 h. The solvent was removed, and a 15 mL aliquot of saturated KPF6 solution was added to the resulting material, then stirred for 20 min. The aqueous phase was extracted with DCM (3 × 10 mL). The combined organic extract was dried over Na2SO4, filtered, and concentrated under high vacuum to afford a yellow product. Yield, 31.2 mg, 88%. Anal. Calcd for C26H22IrN4PF6: C 42.92, H 3.05, N 7.70; Found: C 42.65; H 3.01, N 7.51%. 1H NMR (400 MHz, CD3CN) δ 9.08 (d, J = 5.7 Hz, 2H), 8.06 (q, J = 7.9 Hz,4H), 7.66 (d, J = 7.8 Hz, 2H), 7.45 (t, J = 6.4 Hz, 2H), 6.90 (t, J = 7.5 Hz, 2H), 6.75 (t, J = 7.3 Hz, 2H), 6.05 (d, J = 7.7 Hz, B

DOI: 10.1021/acs.inorgchem.6b00527 Inorg. Chem. XXXX, XXX, XXX−XXX

Article

Inorganic Chemistry Table 1. Crystallographic Data for Δ-1, Λ-3·1.5CH2Cl2, and ΔΔ-6·CH2Cl2·0.5Et2O complex molecular formula Mr crystal system space group a/Å b/Å c/Å β/deg V/Å3 Z Dc (g cm−3) μ (mm−1) no. data of collected no. observed reflections a R1[I > 2σ(I)] b wR2 (all data) Flack parameter GOF on F2 a

Δ-1 C26H22F6N4PIr 727.64 tetragonal P43 8.922 12(13) 8.922 12(13) 32.0341(8) 90.00 2550.05(10) 4 1.895 11.343 43 124 3889 0.0279 0.0646 −0.021(9) 1.051

Λ-3·1.5CH2Cl2 C31.5H25Cl3F6N6PIr 931.09 monoclinic C2 23.7369(4) 14.0057(2) 20.0866(3) 97.851(2) 6615.23(18) 8 1.870 11.111 10 424 10 095 0.0764 0.1986 0.003(13) 1.034

ΔΔ-6·CH2Cl2·0.5Et2O C61H47Cl2N8O0.5Ir2 1355.42 orthorhombic C2221 31.1358(6) 44.3487(8) 20.5543(4) 90.00 28382.0(9) 20 1.523 9.970 23 866 21 406 0.0552 0.1524 −0.019(6) 1.071

R1 = ∑||F0| − |Fc||/∑|F0|. bwR2 = [∑w(F02 − Fc2)2/∑w(F02)2]1/2. Synthesis of meso-ΛΔ-[(Ir(ppy)2)2(dpm)](PF6)2. A mixture of Λ-1 (10.0 mg, 0.0139 mmol) and Δ-3 (9.3 mg, 0.0116 mmol) was dissolved in 5 mL of DCM; then, the solution was stirred at room temperature for 50 min. The reaction solution was washed with a saturated KPF6 solution (3 × 15 mL). The organic phase was dried over Na2SO4, filtered, and concentrated. The product was washed with a minimal amount of CHCl3 to remove the minor mononuclear complex, affording a green dark solid in yield of 72% (12.0 mg). Anal. Calcd for C52H38Ir2N8P2F12: C 43.09, H 2.64, N 7.73; Found: C 42.87; H 2.48, N 7.51%. 1H NMR (400 MHz, DMSO-d6) δ 8.30 (d, J = 5.4 Hz, 4H), 8.27 (d, J = 8.2 Hz, 4H), 8.13 (d, J = 4.8 Hz, 6H), 7.99 (t, J = 7.6 Hz, 4H), 7.93 (d, J = 7.7 Hz, 4H), 7.29 (t, J = 6.3 Hz, 4H), 7.06 (t, J = 7.4 Hz, 4H), 6.95 (t, J = 7.3 Hz, 4H), 6.14 (d, J = 7.5 Hz, 4H). 13C NMR (151 MHz, DMSO-d6) δ 166.69, 164.64, 158.40, 151.37, 145.96, 144.32, 139.83, 131.26, 130.86, 125.65, 124.55, 123.67, 120.63. ESIMS: m/z = 1305.3 [M-PF6]+, 579.2 [M-2PF6]2+. The de value was found to be larger than 99% from 1H NMR spectra. Synthesis of ΛΛ-[(Ir(ppy)2)2(bbim)] and ΔΔ-[(Ir(ppy)2)2(bbim)](PF6)2. Triethylamine (TEA) (10.5 μL, 0.076 mmol) was added to a solution of Λ-1 or Δ-1 (30.0 mg, 0.0413 mmol) and H2bbim (4.5 mg, 0.0192 mmol) in a 5 mL DCE solution. The solution was stirred at 70 °C under N2 atmosphere for 3 h. The reaction mixture was concentrated and subjected to a flash silica gel chromatography (DCM to DCM/MeOH = 100:0.5 as eluents). The eluent was concentrated, affording a yellow solid in yield of 84% (20.0 mg). Anal. Calcd for C58H40Ir2N8: C 56.48, H 3.27, N 9.08; Found: C 56.35; H 3.08, N 9.15%. 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 7.4 Hz, 8H), 7.64 (d, J = 7.5 Hz, 4H), 7.54 (t, J = 8.4 Hz, 4H), 7.01 (t, J = 7.1 Hz, 4H), 6.88 (dd, J = 10.8, 3.9 Hz, 4H), 6.70 (dd, J = 6.1, 3.2 Hz, 4H), 6.60 (dd, J = 10.8, 4.3 Hz, 8H), 6.13 (dd, J = 6.1, 3.2 Hz, 4H). 13 C NMR (101 MHz, CDCl3) δ 168.95, 159.70, 150.00, 149.32, 145.16, 144.24, 136.01, 132.78, 129.28, 123.77, 121.76, 121.06, 120.38, 118.27, 115.85. ESI-MS: m/z = 1234.0 [M + H]+. CD for ΛΛ-6 (Δε, M−1 cm−1, DCM): 261 (+111), 288 (−46), 324 (+38), 360 (+47), 416 (−5), 480 nm (−7). CD for ΔΔ-6 (Δε, M−1 cm−1, DCM): 260 (−100), 287 (+42), 324 (−35), 360 (−41), 418 (+6), 482 nm (+7). Crystals of ΔΔ-6 were grown by diffusing Et2O into a DCM solution of ΔΔ-6. Synthesis of meso-ΛΔ-[(Ir(ppy)2)2(bbim)]. TEA (11.3 μL, 0.0816 mmol) was added to a solution of Λ-1 (18.0 g, 0.0247 mmol) and Δ-4 (15.0 mg, 0.0204 mmol) in DCE (5 mL). The solution was stirred at 70 °C under N2 atmosphere for 3 h. A precipitate formed and was filtered, washed with CHCl3 and Et2O, and dried in air, affording a yellow solid in yield of 79% (19.8 mg). Anal. Calcd for C58H40Ir2N8: C 56.48, H 3.27, N 9.08; Found: C 56.51; H 3.45, N 9.24%.

chromatography (DCM/MeOH = 100:0.5 to 100:1). The product eluent was concentrated, affording a yellow solid. Yield, 15.8 mg, 86%. Anal. Calcd for C36H26IrN6PF6: C 42.15, H 2.98, N 9.55; Found: C 42.31; H 2.75, N 9.46%. 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.1 Hz, 2H), 7.67 (dt, J = 17.7, 6.5 Hz, 8H), 7.32 (t, J = 7.7 Hz, 2H), 7.10 (t, J = 7.3 Hz, 2H), 7.02 (t, J = 7.8 Hz, 2H), 6.95 (t, J = 7.2 Hz, 2H), 6.89 (t, J = 6.3 Hz, 2H), 6.50 (d, J = 7.5 Hz, 2H), 6.21 (d, J = 8.4 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 168.30, 149.44, 147.78, 144.65, 144.32, 140.39, 137.35, 134.70, 132.46, 129.99, 126.05, 125.12, 124.36, 122.92, 122.27, 119.03, 117.61, 113.93. ESI-MS: m/z = 735.2 [M + H]+. CD for Δ-4 (Δε, M−1 cm−1, DCM): 251 (−36), 268 (+16), 287 (+11), 349 (−46), 453 nm (8). CD for Λ-4 (Δε, M−1 cm−1, DCM): 251 (+40), 269 (−16), 289 (−11), 350 (47), 455 nm (−9). Synthesis of Chiral and meso Binuclear Ir(III) Complexes. Synthesis of ΛΛ-[(Ir(ppy)2)2(dpm)](PF6)2 and ΔΔ-[(Ir(ppy)2)2(dpm)](PF6)2. Method A: Λ-1 or Δ-1 (21.0 mg, 0.0289 mmol) and dpm (2.0 mg, 0.0127 mmol) were dissolved in 5 mL of DCM; then, the solution was stirred at room temperature for 40 min. The reaction solution was washed with a saturated KPF6 solution (3 × 15 mL). The organic phase was dried over Na2SO4, and then it was filtered and concentrated. The product was washed with a minimal amount of CHCl3 to remove the mononuclear Λ-3 or Δ-3 and unreacted Λ-1 or Δ-1, affording a dark green ΛΛ-5 or ΔΔ-5 in yield of 72% (13.2 mg). Anal. Calcd for C52H38Ir2N8P2F12: C 43.09, H 2.64, N 7.73; Found: C 43.21; H 2.51, N 7.46%. 1H NMR (400 MHz, DMSO-d6) δ 8.32 (d, J = 8.2 Hz, 4H), 8.28 (d, J = 5.5 Hz, 4H), 8.13 (t, J = 5.4 Hz, 2H), 8.04 (t, J = 7.7 Hz, 4H), 7.95 (d, J = 7.8 Hz, 4H), 7.91 (d, J = 5.4 Hz, 4H), 7.11 (t, J = 6.4 Hz, 4H), 7.05 (t, J = 7.4 Hz, 4H), 6.92 (t, J = 7.3 Hz, 4H), 6.07 (d, J = 7.6 Hz, 4H). 13C NMR (151 MHz, DMSO-d6) δ 166.72, 164.48, 158.51, 151.19, 145.93, 144.41, 139.79, 131.23, 130.77, 125.53, 124.73, 123.62, 120.65. ESI-MS: m/z = 1305.3 [M−PF6]+, 579.2 [M−2PF6]2+. CD for ΛΛ-5 (Δε, M−1 cm−1, DCM): 302 (+54), 332 (−40), 429 nm (+16). CD for ΔΔ-5 (Δε, M−1 cm−1, DCM): 302 (−48), 331 (+37), 429 nm (−14). Method B: Λ-L or Δ-D (23.0 mg, 0.0375 mmol) and dpm (2.5 mg, 0.0158 mmol) were dissolved in 5 mL of DCM; then, the solution was stirred at room temperature for 5 min, and TFA (9.6 μL) was added to the solution. The solution was continually stirred at room temperature for 1 h. The reaction solution was washed with a saturated KPF6 solution (3 × 15 mL). The organic phase was dried over Na2SO4, filtered, and concentrated. The product was washed with a minimal amount of CHCl3 to remove the minor amount of mononuclear complex, affording a dark green ΛΛ-5 or ΔΔ5 in yield of 68% (15.5 mg). The de value was found to be larger than 99% from 1H NMR spectra. C

DOI: 10.1021/acs.inorgchem.6b00527 Inorg. Chem. XXXX, XXX, XXX−XXX

Article

Inorganic Chemistry Single-Crystal X-ray Crystallography. The diffraction intensities for Δ-1, Λ-3·1.5CH2Cl2, and ΔΔ-6·CH2Cl2·0.5Et2O were collected on an Oxford Gemini S Ultra CCD Area detector diffractometer with graphite-monochromated Cu Kα radiation (λ = 1.541 78 Å) at 150 K. All of the data were corrected for absorption effect using the multiscan technique. The structures were solved via direct methods (olex2.solve)16 and refined by iterative cycles of least-squares refinement on F2 followed by difference Fourier synthesis.17 All non-hydrogen atoms were refined anisotropically. All hydrogen atoms were included in the final structure factor calculation at idealized positions and were allowed to ride on the neighboring atoms. For ΔΔ-6·CH2Cl2·0.5Et2O, disordered solvent molecules cannot be modeled and treated by the SQUEEZE routine.18 The structure was then refined using the SQUEEZE data. The amounts of solvent molecules were determine by the TG (Calcd 9.0%, Found 8.7%, see Figure S1) and EA (Anal. Calcd for C61H47Cl2Ir2N8O0.5: C, 54.05; H, 3.50; N, 8.27%. Found: C, 53.85; H, 3.21; N, 8.01%) techniques. The crystal data and the details of data collection and refinement for the complexes are summarized in Table 1. Additional crystallographic information is available in the Supporting Information.

Figure 1. 1H NMR spectra of Δ-L and Λ-L in DMSO-d6, prepared by rac-[(Ir(ppy)2)2Cl2] with 3.0 equiv of L-pro at 40 °C for 24 h with 0 (a), 1.6 (b), 3.2 (c), and 4.8 equiv (d) of NaOMe in MeOH.

RESULTS AND DISCUSSION Syntheses and Characterization of Chiral Precursors. To asymmetrically prepare enantiomerically pure mono- and binuclear Ir(ppy)2 complexes, the attainment of appropriate chiral precursor is the key step. Generally, an excellent precursor should be configurationally stable under the reaction conditions, have high reactivity when the labile ligand is replaced, and be facile to synthesize by the aid of the commercially available materials. Lusby and co-workers have used enantiopure ser to resolve the diastereomers ΛIr(ppy)2(D-ser) and Δ-Ir(ppy)2(D-ser) or Λ-Ir(ppy)2(L-ser) and Δ-Ir(ppy)2(L-ser) on a column chromatography.10a However, only partial resolution was achieved, and it was hard to control the experiment.10b On the one hand, Meggers’ group has used chiral pro as an auxiliary ligand to synthesize asymmetric Λ-[Ru(bpy)2L]2+ (L is a N,N-bidentate ligand)14 and Λ-[Ir(L1)2L2]+ (L1 is (2-phenylbenzo[d]oxazol-5-yl) carboxamide or (2-phenylbenzo[d]thiazole-5-yl)carboxamide, L2 is 2,2,2-trifluoro-N-(3-(pyridin-2-yl)-1H-pyrazol-5-yl)-acetamide) complexes.10e On the other hand, reactions of [(Ir(ppy)2Cl)2] with L-pro have led to unequal mixtures of diastereomers without use of chromatography.9a,f These stimulate us to reobserve the reaction of [(Ir(ppy)2Cl)2] with enantiopure pro.9a First, we observed the reaction of rac[(Ir(ppy)2Cl)2] with 3.0 equiv of L-pro in MeOH solution at 40 °C in the presence of the various amounts of NaOMe as a base and monitored the reaction by NMR spectroscopy. As shown in Figure 1, only a small quantity of Λ-L diastereomer was observed, and no Δ-Ir(ppy)2(L-pro) (Δ-L) diastereomer was detected without base, indicating that the reaction was sluggish and that the reaction of L-pro and rac-Ir(ppy)2 segment was diastereoselective under the experimental conditions. When 1.6 equiv of NaOMe was introduced, the reaction went smoothly with ca. 60% conversion in 24 h (determined by NMR spectra integral, vide infra). Simultaneously, another diastereomer Δ-L appeared. The 1H NMR spectra showed that the dr value was ∼5:1, indicating that the Λ-Ir(ppy)2 segment was completely converted into Λ-L (50% in theory). To further prove the reaction is diastereoselective, the unreacted material of the reaction (Ir/Pro/NaOMe = 1:3:3) at 40 °C in 24 h was isolated by column chromatography and characterized by CD spectroscopy. It is indeed optical activity (see Figure S2), inferring that the unreacted material is Δ configuration rich. An incremental amount of base significantly increased the total conversion of

this reaction. The conversion was completed with 4.8 equiv of base in 24 h. The dr value of Λ-L/Δ-L was varied from 5:1 to 1:1, indicating the diastereoselective reaction of L-pro and racIr(ppy)2 segment was much base-dependent. Therefore, we set the reaction at 50 °C for 24 h with 4.0 equiv of NaOMe to ensure completed conversion of rac-[(Ir(ppy)2Cl)2] into Λ-L and Δ-L. We attempted to separate the diastereomers by the chromatography technique; however, we were unsuccessful. Inspired by Beck and co-workers who have reported the crystal structure of Λ-L·2H2O crystallized from a saturated DCM solution of rac-Ir(ppy)2(L-pro),9a indicating that the diastereomers may have different solubility in the solvents, we found that the enantiomers Λ-L and Δ-D have less solubility than their corresponding diastereomers in CHCl3. Therefore, washing with CHCl3 solvent to remove the diastereomer Δ-L (or Λ-[Ir(ppy)2(D-pro)] (Λ-D)), Λ-L (or Δ-D) was obtained in yield of 35%. Furthermore, the filtrate, containing Δ-L (or Λ-D) and minor amount of Λ-L (or Δ-D), can be reused as a starting material to synthesize another enantiomer by removal of L-pro (or D-pro) ligand in the presence of TFA−MeCN, followed by addition of D-pro (or L-pro) to convert into Δ-D (or Λ-L) in yield of 32%, as shown in Scheme 1. The NMR and MS techniques were used to verify their composition. The auxiliary ligand pro in Δ-D and Λ-L complexes can be substituted by other ligands in acid condition because its binding strength is decreased by protonation of the carboxylate group.11 Thus, Δ-D and Λ-L can be used as precursors to asymmetrically synthesize Ir(ppy)2 complexes in acid condition. The 1H NMR spectra of enantiomers Δ-D and Λ-L are identical. However, the NMR spectra of diastereomers Λ-L and Δ-L and also those of Δ-D and Λ-D are distinguishable. As shown in Figure 2, the resonances of the α-H of pyridine rings appear as two doublet peaks at 9.03 and 8.66 ppm for Λ-L and at 8.69 and 8.58 ppm for Δ-L. The integrals of these peaks can be used to calculate the dr value of Λ-L and Δ-L, and it is found to be 100:1. The similar case is also found in the diasteromers Δ-D and Λ-D. CD spectrum was also used to observe the optical activity of Δ-D and Λ-L. As shown in Figure 3, enantiomers Λ-L and Δ-D have Cotton effect at 264, 284, 318, 382, 418, and 500 nm. They are almost mirror images. The CD spectra of diastereomers Λ-L and Δ-L were also measured (see Figure S3); they are also mirror images, suggesting that the

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DOI: 10.1021/acs.inorgchem.6b00527 Inorg. Chem. XXXX, XXX, XXX−XXX

Article

Inorganic Chemistry Scheme 1. Diagram for the Synthesis of Λ-L and Δ-D Precursors

configurations at chiral Ir(III) centers are the main determinant in the appearance of the spectra. Δ-D and Λ-L can be used as precursors to synthesize Ir(ppy)2 complex in acidic conditions; however, that also limited their application on the synthesis of acid-sensitive complexes and sometimes on polynuclear complexes (e.g., complex 6). Thus, the universal precursors with high reactivity like Δ-1 and Λ-1 are highly desirable. Having the enantiomerically pure complexes in hand, they can be converted into labile MeCN complexes by removal of the auxiliary ligand in acidic conditions. Indeed, when Λ-L was treated with 2.5 equiv of TFA in the presence of an excess of coordinating solvent MeCN at room temperature for 1 h, Λ-1 was obtained in a yield of 88%. Δ-1 can be obtained in a similar way. Their 1H NMR spectra are identical. CD spectra of the enantiomers are mirror images, having Cotton effect at 258, 303, 328, and 423 nm (see Figure S4). To observe the absolute configuration at Ir(III) center, crystal structure of Δ-1 was measured by single-crystal X-ray diffraction, though the crystal structure of rac-1 has been reported.20 It crystallizes in the chiral P43 space group, different from that of rac-1 in P1̅. The absolute configuration of Ir(III) center is in Δ fashion. The Flack parameter is −0.021(9),21 demonstrating the assignment of chirality at the metal center is correct and the configuration at Ir(III) center is stable upon removal of the auxiliary chiral ligand D-pro and coordination with MeCN ligand. As shown in Figure 4, the Ir−N and Ir−C

Figure 2. Aromatic region of 1H NMR spectra of Λ-L (a) and Δ-L (b) in DMSO-d6.

Figure 4. Crystal structure of Δ-1 (Ir1−N4 = 2.128(8) Å, Ir1−C12 = 2.014(10) Å, Ir1−N2 = 2.129(8) Å, Ir1−N3 = 2.038(12) Å, Ir1−N1 = 2.061(13) Å, Ir1−C1 = 2.013(9) Å, N2−Ir1−N4 = 88.7(3)°, C12− Ir1−N1 = 80.3(3)°, C1−Ir1−N3 = 80.0(3)°). ORTEP drawing with 50% probability thermal elipsoids.19

distances are in accord with the reported.20 The bond lengths of Ir1−N4 (2.128(8) Å) and Ir1−N2 (2.129(8) Å) are slightly longer than those of Ir1−N3 (2.038(12) Å) and Ir1−N1 (2.061(13) Å), indicating the carbon atom has a strong trans effect. Moreover, the relationship between the absolute configurations at Ir(III) centers determined via crystal structure and their CD spectra can be established.

Figure 3. CD spectra of of Δ-D and Λ-L in DCM (6.0 × 10−4 M).

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DOI: 10.1021/acs.inorgchem.6b00527 Inorg. Chem. XXXX, XXX, XXX−XXX

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Inorganic Chemistry Synthesis and Characterization of Chiral Mononuclear Complexes. With the enantiopure precursors in hand, we next employed them as precursors to asymmetrically synthesize mononuclear complexes. Although Λ-2 and Δ-2 have been synthesized by Meggers’ group using the phenol− oxazoline as the auxiliary,10c to compare, we also synthesized them using the prepared precursors. Indeed, the substituted reaction of the auxiliary ligand pro in Λ-L or Δ-D by 1.5 equiv of bidentate ligand bpy went smoothly at room temperature in the presence of 3 equiv of TFA, affording mononuclear complex Λ-2 or Δ-2 in yield of 88%. Moreover, enantiopure Λ2/Δ-2 was also synthesized from the corresponding precursor Λ-1/Δ-1 in neutral condition in 87%. In similar cases, the precursors Λ-L/Δ-D and Λ-1/Δ-1 were used to prepare enantiopure Λ-3/Δ-3 and Λ-4/Δ-4 complexes in good yields. The complexes Λ-2/Δ-2, Λ-3/Δ-3, and Λ-4/Δ-4 are optically active. The CD spectra of the enantiomers are mirror images with strong Cotton effect, as shown in Figures 5, S5, and S6.

shown in Figure 7, the absolute configuration at Ir(III) center is in Λ fashion and consistent with that of the precursor. N5 and

Figure 7. View of the molecular structure of Λ-3. Selected bond distances (Å) and angles (deg): Ir1−C15 = 2.000(13), Ir1−C26 = 2.043(11), Ir1−N1 = 2.155(9), Ir1−N3 = 2.139(8), Ir1−N5 = 2.076(10), Ir1−N6 = 2.064(10), N5−Ir1−N6 = 170.3(4), C15−Ir1− C26 = 89.4(5), N1−Ir1−N3 = 75.9(4), N5−Ir1−C15 = 81.3(5), N6− Ir1−C26 = 81.2(5). ORTEP drawing with 50% probability thermal elipsoids.19

N6 atoms are in trans position. The Flack parameter is 0.003(13),21 demonstrating the assignment of chirality at Ir(III) center is reasonable and the configuration at Ir(III) center is intact during the synthesis. The Ir−N and Ir−C distances are in accord with the reported.22 The bond lengths of Ir1−N1 (2.155(9) Å) and Ir1−N3 (2.139(8) Å) are slightly longer than those of Ir1−N5 (2.076(10) Å) and Ir1−N6 (2.064(10) Å), indicating the carbon atom has a strong trans effect. The bite angle for dpm (75.9(4)°) is markedly smaller than those of ppy (81.3(5) and 81.2)°). Synthesis and Characterization of Binuclear Complexes. Generally, reaction of the racemic precursor complex Ir(ppy)2 with a bridging ligand affords two diastereoisomers (a meso ΔΛ and an enantiomeric pair ΔΔ and ΛΛ). The use of an enatiopure precursor may avoid the formation of diastereoisomer. Indeed, treatment of Δ-D or Λ-L with dpm in 1:0.42 ratio in the presence of TFA afforded ΔΔ-5 or ΛΛ-5 in yield of 68% (see Scheme 2). Moreover, pure ΔΔ-5 or ΛΛ-5

Figure 5. CD spectra of Δ-3 and Λ-3 in DCM (5.0 × 10−5 M).

The enantiopurities of Λ-2/Δ-2 and Λ-3/Δ-3 complexes were examined by chiral HPLC analysis, and the ee values were found to be greater than 99% (see Figures 6 and S7). The results also indicate that the precursors Λ-L/Δ-D and Λ-1/Δ-1 are high in purity (≥99%), configurations at Ir(III) center are stable, and no racemization occurs during the reactions. To observe the absolute configuration at Ir(III) center, single-crystal structural analysis for Λ-3·1.5CH2Cl2 was performed. It crystallizes in the chiral space group C2. As

Scheme 2. Diagram for the Synthesis of Chiral and meso Binuclear Complexes 5

can also be asymmetrically synthesized in one-pot in neutral conditions using the corresponding Δ-1 or Λ-1 as a precursor with dpm in DCM at room temperature in 72% yield. It must be stressed that the mono- and binuclear Ir(III) complexes can be synthesized using these precursors and dpm by adjusting the molar ratio of the reactants, followed by a facile separation.

Figure 6. HPLC traces of rac-3 (a), Δ-3 (b), and Λ-3 (c). HPLC conditions: Daicel Chiralpak AD-H column (250 × 4.6 mm), flow rate = 1.0 mL/min, UV absorption = 300 nm. Solvent A = n-heptane, solvent B = EtOH/TEA/TFA (50:0.3:0.1); linear gradient of 25 to 35% B in 20 min. F

DOI: 10.1021/acs.inorgchem.6b00527 Inorg. Chem. XXXX, XXX, XXX−XXX

Article

Inorganic Chemistry Meso ΔΛ-5 was synthesized by a two-step reaction from various starting materials, as shown in Scheme 2. Up to now, binuclear complexes bridged Ir(ppy)2 units have been muchinvestigated;20,23 however, the syntheses of purely homochiral (ΔΔ or ΛΛ) and heterochiral (ΔΛ) binuclear Ir(III) complexes are less-explored.4b,8,23n Full separation of three stereoisomers is hard work and sometimes impossible. Although Collin and co-workers have partially separated the stereoisomers of [(ppy)2Ir(L)Ir(ppy)2]2+ (L = 3,8-dipyridyl4,7-phenanthroline) using ion-pair chromatography with optically pure Δ-TRISPHAT anion as a mobile phase, the yield was low (