Synthesis of Novel Chiral Phenanthroline Ligands and a Copper Complex

Abstract

A novel class of chiral multidentate ligands has been designed and synthesized from the important classic ligand 1,10-phenanthroline and amino acids. The ligands were proven to be able to coordinate with copper(2+) ion by the formation of a novel chiral copper complex, the structure of which was determined by single-crystal X-ray diffraction.

Key words

phenanthroline - amino acids - ligands - asymmetric synthesis - copper complex

Publication History

Received: 23 September 2021

Accepted after revision: 27 October 2021

Accepted Manuscript online:
27 October 2021

Article published online:
11 November 2021

• References and Notes

• 1a Summers LA. Adv. Heterocycl. Chem. 1978; 22: 1
• 1b Sammes PG, Yahioglu G. Chem. Soc. Rev. 1994; 23: 327
• 1c Luman CR, Castellano FN. Comprehensive Coordination Chemistry II, Vol. 1. McCleverty JA, Meyer TJ. Elsevier; Oxford: 2004. Chap. 1.1, 25
• 2a Lavie-Cambot A, Cantuel M, Leydet Y, Jonusauskas G, Bassani DM, McClenaghan ND. Coord. Chem. Rev. 2008; 252: 2572
• 2b Bencini A, Lippolis V. Coord. Chem. Rev. 2010; 254: 2096
• 3a Sigman DS, Mazunder A, Perrin DM. Chem. Rev. 1993; 93: 2295
• 3b Pogozelski WK, Tullius TD. Chem. Rev. 1998; 98: 1089
• 3c Ji L.-N, Zou X.-H, Liu J.-G. Coord. Chem. Rev. 2001; 216: 513
• 3d Sigman DS, Landgraf R, Perrin DM, Pearson L. Metal Ions in Biological Systems, Vol. 33. Sigel A, Sigel H. Dekker; New York: 1996. Chap. 16, 485
• 4a Amabilino DB, Stoddart JF. Chem. Rev. 1995; 95: 2725
• 4b Raymo FM, Stoddart JF. Chem. Rev. 1999; 99: 1643
• 4c Armaroli N. Chem. Soc. Rev. 2001; 30: 113
• 4d Saha ML, Neogi S, Schmittel M. Dalton Trans. 2014; 43: 3815

For selected examples of nonasymmetric reactions catalyzed by metal/phen-based ligands:
• 5a Carney JM, Donoghue PJ, Wuest WM, Wiest O, Helquist P. Org. Lett. 2008; 10: 3903
• 5b Shirakawa E, Ito K.-i, Higashino T, Hayashi T. J. Am. Chem. Soc. 2010; 132: 15537
• 5c Shibahara F, Yamaguchi E, Murai T. Chem. Commun. 2010; 46: 2471
• 5d Peng J, Kishi Y. Org. Lett. 2012; 14: 86
• 5e Limberger J, Leal BC, Back DF, Dupont J, Monteiro AL. Adv. Synth. Catal. 2012; 354: 1429
• 5f Yu P, Zhang G, Chen F, Cheng J. Tetrahedron Lett. 2012; 53: 4588
• 5g Williams TJ, Fairlamb IJ. S. Tetrahedron Lett. 2013; 54: 2906
• 5h Cho SH, Hartwig JF. J. Am. Chem. Soc. 2013; 135: 8157
• 5i Li X, Yang F, Wu Y, Wu Y. Org. Lett. 2014; 16: 992
• 5j Yamauchi T, Shibahara F, Murai T. J. Org. Chem. 2014; 79: 7185
• 5k Yamauchi T, Shibahara F, Murai T. Org. Lett. 2015; 17: 5392
• 5l Cheng C, Hartwig JF. J. Am. Chem. Soc. 2015; 137: 592
• 5m Egger L, Guénée L, Bürgi T, Lacour J. Adv. Synth. Catal. 2017; 359: 2918
• 5n Shevlin M, Guan X, Driver TG. ACS Catal. 2017; 7: 5518
• 5o Liu T, Myers MC, Yu J.-Q. Angew. Chem. Int. Ed. 2017; 56: 306
• 5p Wang F, Wang D, Zhou Y, Liang L, Lu R, Chen P, Lin Z, Liu G. Angew. Chem. Int. Ed. 2018; 57: 7140
• 5q Shan X.-H, Yang B, Zheng H.-X, Qu J.-P, Kang Y.-B. Org. Lett. 2018; 20: 7898
• 5r Yamamoto K, Li JK, Garber JA. O, Rolfes JD, Boursalian GB, Borghs JC, Genicot C, Jacq J, van Gastel M, Neese F, Ritter T. Nature 2018; 554: 511
• 5s Zhang H, Zhou Y, Tian P, Jiang C. Org. Lett. 2019; 21: 1921
• 5t Lo PK. T, Chen Y, Willis MC. ACS Catal. 2019; 9: 10668
• 5u Drapeau MP, Bahri J, Lichte D, Gooβen LJ. Angew. Chem. Int. Ed. 2019; 58: 892
• 5v Karmel C, Chen Z, Hartwig JF. J. Am. Chem. Soc. 2019; 141: 7063
• 5w Mondal R, Sinha S, Das S, Chakraborty G, Paul ND. Adv. Synth. Catal. 2020; 362: 594
• 5x Zhu L, Li J, Yang J, Au-Yeung HY. Chem. Sci. 2020; 11: 13008
• 5y Cho YH, Kim JH, An H, Ahn K.-H, Kang EJ. Adv. Synth. Catal. 2020; 362: 2183
• 5z Larsen MA, Oeschger RJ, Hartwig JF. ACS Catal. 2020; 10: 3415
• 5aa Sarkar A, Formenti D, Ferretti F, Kreyenschulte C, Bartling S, Junge K, Beller M, Ragaini F. Chem. Sci. 2020; 11: 6217
• 5ab DeMent PM, Liu C, Wakpal J, Schaugaard RN, Schlegel HB, Nguyen HM. ACS Catal. 2021; 11: 2108

For selected examples of enantioselective reactions catalyzed by metal/phen-based chiral ligands, see:
• 6a Schoffers E. Eur. J. Org. Chem. 2003; 1145
• 6b Chelucci G, Thummel RP. Chem. Rev. 2002; 102: 3129
• 6c Gladiali S, Chelucci G, Chessa G, Delogu G, Soccolini F. J. Organomet. Chem. 1987; 327: C15
• 6d Gladiali S, Pinna L, Delogu G, Graf E, Brunner H. Tetrahedron: Asymmetry 1990; 1: 937
• 6e Gladiali S, Pinna L, Delogu G, De Martin S, Zassinovich G, Mestroni G. Tetrahedron: Asymmetry 1990; 1: 635
• 6f Kandzia C, Steckhan E, Knoch F. Tetrahedron: Asymmetry 1993; 4: 39
• 6g Peña-Cabrera E, Norrby P.-O, Sjögren M, Vitagliano A, De Felice V, Oslob J, Ishii S, O’Neill D, Åkermark B, Helquist P. J. Am. Chem. Soc. 1996; 118: 4299
• 6h Chelucci G, Pinna GA, Saba A, Sanna G. J. Mol. Catal. A: Chem. 2000; 159: 423
• 6i Gladiali S, Chelucci G, Mudadu MS, Gastaut M.-A, Thummel RP. J. Org. Chem. 2001; 66: 400
• 6j Chelucci G, Iuliano A, Muroni D, Saba A. J. Mol. Catal. A: Chem. 2003; 191: 29
• 6k Puglisi A, Benaglia M, Annunziata R, Bologna A. Tetrahedron Lett. 2003; 44: 2947
• 6l Nishikawa Y, Yamamoto H. J. Am. Chem. Soc. 2011; 133: 8432
• 6m Naganawa Y, Namba T, Aoyama T, Shoji K, Nishiyama H. Chem. Commun. 2014; 50: 13224
• 6n Naganawa Y, Komatsu H, Nishiyama H. Chem. Lett. 2015; 44: 1652
• 6o Naganawa Y, Namba T, Kawagishi M, Nishiyama H. Chem. Eur. J. 2015; 21: 9319
• 6p Naganawa Y, Aoyama T, Nishiyama H. Org. Biomol. Chem. 2015; 13: 11499
• 6q Naganawa Y, Abe H, Nishiyama H. Synlett 2016; 27: 1973
• 6r Naganawa Y, Nishiyama H. Chem. Rec. 2016; 16: 2573
• 6s Naganawa Y, Aoyama T, Kato K, Nishiyama H. ChemistrySelect 2016; 1: 1938
• 6t Wojaczyńska E, Skarżewski J, Sidorowicz Ł, Wieczorek R, Wojaczyński J. New J. Chem. 2016; 40: 9795
• 6u Tamura M, Ogata H, Ishida Y, Takahashi Y. Tetrahedron Lett. 2017; 58: 3808
• 6v Naganawa Y, Abe H, Nishiyama H. Chem. Commun. 2018; 54: 2674
• 6w Annapureddy RR, Jandl C, Bach T. J. Am. Chem. Soc. 2020; 142: 7374
• 7 Krapcho AP, Lanza JB. Org. Prep. Proced. Int. 2007; 39: 603
• 8 2,2′-(1,10-Phenanthroline-2,9-diyl)dibenzaldehyde (7) To a solution of 2,9-dichloro-1,10-phenanthroline (6; 1.50 g, 6.04 mmol) in 1,4-dioxane (80.0 mL) and H₂O (8.0 mL) were added (2-formylphenyl)boronic acid (2.268 g, 15.12 mmol), Na₂CO₃ (2.564 g, 24.19 mmol), and Pd(PPh₃)₄ (0.60 mmol, 699 mg), and the mixture was stirred at 100 °C under N₂ for 12 h. Upon completion of the reaction, the mixture was cooled to r.t. and filtered through a pad of Celite. The 1,4-dioxane was evaporated under reduced pressure, and the resulting mixture was extracted with CH₂Cl₂ (×3). The combined organic layers were washed with brine, dried (Na₂SO₄), and concentrated. The residue was purified by column chromatography [silica gel, CH₂Cl₂–MeOH (80:1)] to give a yellow solid; yield: 1.361 g (58%); mp 160–161 °C. ¹H NMR (400 MHz, CHCl₃): δ = 10.42 (s, 2 H), 8.38 (d, J = 8.4 Hz, 2 H), 8.06 (dd, J = 8.0, 1.2 Hz, 2 H), 7.94 (d, J = 8.0 Hz, 2 H), 7.91 (d, J = 7.2 Hz, 2 H), 7.88 (s, 2 H), 7.71 (td, J = 7.6, 1.2 Hz, 2 H), 7.56 (t, J = 7.6 Hz, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 192.53, 156.30, 145.92, 143.30, 136.84, 135.72, 133.18, 130.88, 129.23, 128.59, 127.78, 126.75, 123.93. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₆H₁₇N₂O₂: 389.1285; found: 389.1276.
• 9 Diamino Diester 8a; Typical Procedure A dried 50 mL Schlenk flask was charged with methyl l-phenylalaninate hydrochloride (397 mg, 1.84 mmol), intermediate 7a (300 mg, 0.77 mmol), and MgSO₄ (222 mg, 1.84 mmol) under N₂. CH₂Cl₂ (10 mL) was added, the mixture was cooled to 0 °C, and Et₃N (255 μL, 1.84 mmol) was added. The mixture was stirred at 0 °C for 0.5 h; it was then allowed to warm to r.t. and stirred for 12 h. The mixture was then cooled again to 0 °C before NaBH(OAc)₃ (1.632 g, 7.7 mmol) was added. The resulting mixture was stirred at 0 °C for 0.5 h, warmed slowly to r.t., and stirred overnight. The reaction was quenched with H₂O, and the product was extracted with CH₂Cl₂ (×3). The organic layers were combined, dried (Na₂SO₄), and concentrated, and the residue was purified by column chromatography [silica gel, CH₂Cl₂–MeOH (80:1)] to give a yellow solid; yield: 386 mg (70%); mp 106–107 °C; [α]_D ²⁰ +45.6 (c = 0.25, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 8.33 (d, J = 8.4 Hz, 2 H), 7.91 (s, 2 H), 7.85 (d, J = 8.0 Hz, 2 H), 7.65 (d, J = 7.6 Hz, 2 H), 7.51 (d, J = 5.6 Hz, 2 H), 7.44 (t, J = 6.4 Hz, 2 H), 7.34 (t, J = 7.2 Hz, 2 H), 7.11–7.05 (m, 6 H), 6.90–6.82 (m, 4 H), 4.06–3.82 (m, 4 H), 3.51–3.67 (m, 2 H), 3.08 (s, 6 H), 2.89 (s, 2 H), 2.41–2.59 (m, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 171.70, 158.72, 144.92, 140.88, 137.50, 136.26, 133.13, 132.74, 130.48, 129.58, 129.39, 129.21, 128.28, 127.89, 126.76, 126.73, 124.36, 61.73, 51.60, 49.60, 36.93. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₄₆H₄₃N₄O₄: 715.3279; found: 715.3263.
• 10 Chiral Phenanthroline Ligand 9a; Typical ProcedureTo a solution of diester 8a (100 mg, 0.14 mmol) in MeOH (10 mL) and H₂O (2 mL) was added NaOH (112 mg, 2.8 mmol) at r.t., and the mixture was heated to 60 °C with stirring for 12 h. Upon completion of the reaction, the pH of the solution was adjusted to 3–4 by addition of 1.0 M aq HCl. The solvent was then removed under reduced pressure and the crude product was dissolved in MeOH. The solution was filtered and concentrated, and the crude product was crystallized from MeOH to give a yellow solid; yield: 96 mg (91%); mp 200–201 °C; [α]_D ²⁰ –88.8 (c 0.25, MeOH). ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.71 (d, J = 8.4 Hz, 2 H), 8.17 (s, 2 H), 8.08 (d, J = 8.4 Hz, 2 H), 7.72 (d, J = 7.2 Hz, 2 H), 7.67–7.61 (m, 2 H), 7.56–7.45 (m, 4 H), 7.09–7.00 (m, 6 H), 6.88–6.79 (m, 4 H), 4.18 (d, J = 13.2 Hz, 2 H), 4.09 (d, J = 12.8 Hz, 2 H), 3.45 (t, J = 7.0 Hz, 2 H), 2.94–2.76 (m, 2 H), 2.76–2.64 (m, 2 H). ¹³C NMR (101 MHz, DMSO-d ₆): δ = 170.09, 157.68, 143.91, 140.81, 138.30, 136.16, 132.41, 131.46, 130.53, 129.29, 129.24, 128.92, 127.92, 127.67, 126.75, 126.43, 124.37, 60.60, 47.19, 34.97. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₄₄H₃₉N₄O₄: 687.2966; found: 687.2962.
• 11 Copper Complex 10a To a solution of 9a (100 mg, 0.13 mmol) in MeOH (10 mL) was added NaH (112 mg, 60% dispersion in mineral oil, 2.8 mmol), and the mixture was stirred at r.t. for 0.5 h. A solution of CuCl₂ in MeOH (1.0 mL) was added dropwise to the mixture, which was then heated to 40 °C and stirred for 5 h. After cooling to r.t., the mixture was filtered through a pad of Celite and concentrated under reduced pressure. The crude product was purified by crystallization from MeOH–Et₂O to give a deep-blue solid; yield: 21 mg (40%); mp 210–211 °C. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₄₄H₃₈ClCuN₄O₄: 784.1872; found: 784.1863.
• 12 CCDC 2106610 contains the supplementary crystallographic data for compound 10a. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures