Racemisation of 1-Arylethylamines with Shvo-type Organoruthenium Catalysts

Abstract

Variation of the electronic nature of the tetraphenyl­cyclopentadienone ligand in organoruthenium complexes influences their utility for racemisation of model chiral amines. Our study highlights the need to balance reactivity and selectivity in the design of racemisation catalysts. Electron-poor Shvo-type catalysts are, at first sight, more effective for racemisation, but yield more by-product; electron-rich complexes are less proficient at racemisation, but lead to less by-product.

Key words

racemisation - amine - alcohol - organoruthenium - DFT

• References and Notes

• 1 Ebbers EJ, Ariaans GJ. A, Houbiers JP. M, Bruggink A, Zwanenberg B. Tetrahedron 1997; 28: 9417
• 2 Stecher H, Faber K. Synthesis 1997; 1
• 3a Hoyos P, Pace V, Alcantara AR. Adv. Synth. Catal. 2012; 354: 2585
• 3b Ahmed M, Kelly T, Ghanem A. Tetrahedron 2012; 68: 6781
• 3c Cohen DT, Eichman CC, Phillips EM, Zarefsky ER, Scheidt KA. Angew. Chem. Int. Ed. 2012; 16: 7309
• 3d Pellissier H. Adv. Synth. Catal. 2011; 353: 659
• 3e Lee JH, Han K, Kim M.-J, Park J. Eur. J. Org. Chem. 2010; 999
• 3f Parvulescu A, Janssens J, Vanderleyden J, de Vos D. Top. Catal. 2010; 53: 931
• 3g Kamaruddin AH, Uzir MH, Aboul-Enein HY, Halim HN. Chirality 2009; 21: 449
• 3h Kamal A, Azhar MA, Krishnaji T, Malik MS, Azeeza S. Coord. Chem. Rev. 2008; 252: 569
• 3i Pellissier H. Tetrahedron 2008; 64: 1563
• 3j Martin-Matute B, Bäckvall J.-E. Curr. Opin. Chem. Biol. 2007; 11: 226
• 3k Turner NJ. Curr. Opin. Chem. Biol. 2004; 8: 114
• 4 Allen JV, Williams JM. J. Tetrahedron Lett. 1996; 37: 1859
• 5 Reetz MT, Schimossek K. Chimia 1996; 50: 668
• 6 Paetzold J, Bäckvall J.-E. J. Am. Chem. Soc. 2005; 127: 17620
• 7 Caddick S, Jenkins K. Chem. Soc. Rev. 1996; 25: 447
• 8 Kim Y, Park J, Kim M.-J. ChemCatChem 2011; 3: 271
• 9a Stirling M, Blacker J, Page MI. Tetrahedron Lett. 2007; 48: 1247
• 9b Blacker AJ, Stirling MJ, Page MI. Org. Process Rev. Dev. 2007; 11: 642
• 10 Poulhès F, Vanthuyne N, Bertrand MP, Gastaldi S, Gil G. J. Org. Chem. 2011; 76: 7281
• 11 Roengpithya C, Patterson D, Livingston AG, Taylor PC, Irwin JL, Parrett MR. Chem. Commun. 2007; 3462
• 12 Pàmies O, Ell AH, Samec JS. M, Hermanns N, Bäckvall J.-E. Tetrahedron Lett. 2002; 43: 4699
• 13 Johnson JR, Grummitt O. Organic Synth., Coll. Vol. 3 1955; 806
• 14 Casey CP, Singer SW, Powell DR, Hayashi RK, Kavana M. J. Am. Chem. Soc. 2001; 123: 1090
• 15 Choi JH, Choi YK, Kim YH, Park ES, Kim EJ, Kim M.-J, Park J. J. Org. Chem. 2004; 69: 1972
• 16 Martín-Matute B, Edin M, Bogár K, Bäckvall J.-E. Angew. Chem. Int. Ed. 2004; 43: 6535
• 17 Dai W, Srinivasan R, Katzenellenbogen JA. J. Org. Chem. 1989; 54: 2204
• 18 Gibbins EJ, Irwin JL, Livingston AG, Muir JC, Patterson DA, Roengpithya C, Taylor PC. Synlett 2005; 2993
• 19 General Procedure for the Racemisation of Amine 5b: Shvo-type complex 1a–j (13 μmol) was placed in a flame-dried Schlenk tube under dry N₂ gas. Anhydrous toluene (2 mL) and (S)-(–)-1-phenylethylamine ( S )-5b (16.8 μL, 130 μmol) were added via syringe. The reaction was heated to 100 °C and stirred for 24 h. Samples were taken after 1, 2, 4 and 24 h and were analysed by GC in order to ascertain the ee of amine 5b and the relative quantities of 5b, imine 7 and amine 8. General Procedure for the Preparation of Substituted Shvo-Type Complexes 1:¹⁰ Triruthenium dodecacarbonyl (0.30 g, 0.47 mmol) and para-substituted tetraphenylcyclopentadienone 4 (1.43 mmol) was dissolved in MeOH (80 mL). The mixture was heated at reflux for 72 h and the precipitate collected by filtration under suction. The residue was washed with MeOH (3 × 10 mL). Complex 1a: The compound was prepared by the general procedure, using 2,3,4,5-tetra(4-methoxyphenyl)cyclo-pentadienone (0.72 g, 1.43 mmol) and triruthenium dodecacarbonyl (0.30 g, 0.47 mmol) to yield 1a as a yellow powder (0.69 g, 74%); mp 218–220 °C. IR: 834, 2029, 2006, 1986, 1962, 1608, 1577, 1516, 1030 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 6.95 (AA′ of AA′BB′, J = 7.6 Hz, 8 H, ArH), 6.85 (AA′ of AA′BB′, J = 7.6 Hz, 8 H, ArH), 6.45 (m, 16 H, ArH), 3.70 (s, 12 H, Me), 3.60 (s, 12 H, Me), –18.60 (s, 1 H, RuHRu). ¹³C NMR (75 MHz, CDCl₃): δ = 201.3, 159.3, 158.5, 154.0, 133.6, 132.7, 123.3, 122.9, 113.4, 113.3, 102.5, 87.9, 55.5, 55.4. MS (EI): m/z (%) = 1326 (15) [M + H⁺], 1212 (20), 607 (100), 635 (25). Anal. Calcd for C₇₀H₅₈O₁₄Ru₂: C, 63.44; H, 4.41. Found: C, 63.37; H, 4.37. Complex 1c: The compound was prepared by the general procedure, using 2,5-diphenyl-3,4-di(4-methoxyphenyl)cyclopentadienone (0.63 g, 1.43 mmol) and triruthenium dodecacarbonyl (0.30 g, 0.47 mmol) to yield 1c as a yellow powder (0.64 g, 76%); mp 217–219 °C. IR: 2025, 1995, 1962, 1956, 1608, 1073, 762 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.10 (AA′ of AA′BB′, J = 6.9 Hz, 8 H, ArH), 7.01 (m, 12 H, ArH), 6.90 (BB′ of AA′BB′, J = 6.9 Hz, 8 H, ArH), 6.54 (AA′ of AA′BB′, J = 9.2 Hz, 8 H, ArH), 3.69 (s, 12 H, Me), –18.46 (s, 1 H, RuHRu). ¹³C NMR (75 MHz, CDCl₃): δ = 201.0, 158.9, 133.2, 131.3, 130.5 (2 ×), 127.7, 126.7, 122.6, 112.9, 102.8, 87.9, 55.0. MS (EI): m/z (%) = 1206 (53) [M + H⁺], 1150 (35), 1092 (45), 546 (100), 154 (29). Anal. Calcd for C₆₆H₅₀O₁₀Ru₂: C, 65.77; H, 4.18. Found: C, 65.82; H, 4.15. General Procedure for the Racemisation of Alcohol 14 (Ref. 11): Ruthenium complex (0.02 mmol) and potassium tert-butoxide (3.4 mg, 0.03 mmol) were placed in a flame-dried Schlenk tube under dry nitrogen gas. Anhydrous toluene (2 mL) and (S)-(–)-1-phenylethanol [(S)-14; 60.4 μL, 0.5 mmol] were added with a syringe. Samples were taken after 1, 2, 4 and 24 h and were analysed by GC in order to ascertain the ee of alcohol 14 and the relative quantities of 14 and acetophenone 16. The protocol is shown in the supporting information. Synthesis of Complex 13:^13,14 A solution of 2,3,4,5-tetra(4-methoxyphenyl)cyclopentadienone (0.75 g, 1.50 mmol) and isopropylamine (0.57 mL, 6.70 mmol) in anhyd toluene (10 mL) was stirred well under nitrogen gas at 0 °C. Titanium tetrachloride (1.0 M solution in toluene; 0.37 mL, 0.36 mmol) was added dropwise and the reaction mixture was heated to reflux for 2 h. After being cooled to 15 °C the reaction mixture was diluted with Et₂O (15 mL). The reaction mixture was filtered through celite, and the collected precipitate washed with Et₂O. Concentration of the combined fractions via evaporation of the solvent under vacuum yielded 15 as a red powder (0.52 g, 64%); mp 275–277 °C. Ruthenium carbonyl (0.30 g, 0.47 mmol) and 15 (0.38 g, 0.71 mmol) were dissolved in anhyd CHCl₃ (9 mL) under nitrogen gas. The reaction mixture was heated to reflux and left for 5 d. The solution was cooled and the solvent removed via evaporation under vacuum. The product was purified by flash chromatography (SiO₂, 1^st pentane, 2^nd 10:90 EtOAc–pentane, 3^rd 50:50 EtOAc–pentane) to yield 13 as a dark red powder (0.27 g, 53%); mp 134 °C (dec.). IR: 3352, 2015, 1957, 1515 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.47 (AA′ of AA′BB′, J = 7.7 Hz, 4 H, ArH), 6.86 (m, 8 H, ArH), 6.56 (BB′ of AA′BB′, J = 7.7 Hz, 4 H, ArH), 4.12 (d, J = 7.7 Hz, 1 H, NH), 3.83 (s, 6 H, Me), 3.71 (s, 6 H, Me), 3.30 (oct, J = 7.7 Hz, 1 H, CH), 0.87 (d, J = 7.7 Hz, 6 H, Me). ¹³C NMR (75 MHz, CDCl₃): δ = 198.9, 165.0, 159.9, 159.3, 135.1, 133.4, 123.0, 122.8, 114.5, 113.3, 101.2, 81.1, 55.7, 55.5, 45.5, 25.4. MS (EI): m/z (%) = 743 (2) [M⁺], 560 (29), 368 (48), 135 (100). Anal. Calcd for C₃₈H₃₆ClNO₆Ru: C, 61.74; H, 4.91; N, 1.89; Cl, 4.79 (Inaccurate). Found: C, 60.91; H, 4.95; N, 1.78; Cl, 4.88. Computational Studies: DFT calculations²⁰ were carried out using the Gaussian03 suite of programs.²¹ Geometry optimisations, vibrational frequencies and single-point energies were obtained with the B3LYP functional^22,23 and 3-21G(d,p) basis set. The structures were optimised with constrained planar geometry in order to simulate the conformation of the ligand in the catalyst. Vibrational frequency calculations resulted in only one imaginary frequency corresponding to the rotational constraint imposed along the aryl cyclopentadienone C–C bonds.
• 20a Hohenberg P, Kohn W. Phys. Rev. 1964; 136: B864
• 20b Kohn W, Sham LJ. Phys. Rev. 1965; 140: A1133
• 20c Salahub DR, Zerner MC. The Challenge of d and f Electrons . American Chemical Society; Washington DC: 1989
• 20d Parr RG, Yang W. Density-Functional Theory of Atoms and Molecules . Oxford University Press; Oxford: 1989
• 21 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA. Jr, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PM. W, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA. Gaussian 03, Revision B.05. Gaussian Inc; Wallingford CT: 2004
• 22 Becke AD. J. Chem. Phys. 1993; 98: 5648
• 23a Lee C, Yang W, Parr RG. Phys. Rev. B 1998; 37: 785
• 23b Miehlich B, Savin A, Stoll H, Preuss H. Chem. Phys. Lett. 1989; 157: 200