Asymmetric Homogeneous Hydrogenation of 2-Pyridones

Dedicated to Peter Vollhardt for all the inspiration he has given the chemistry world

Abstract

An asymmetric homogeneous hydrogenation of 2(1H)-pyridones has been developed, using a ruthenium complex bearing two chiral N-heterocyclic carbene (NHC) ligands. To the best of our knowledge, the presented reaction is the first example of a homogeneous asymmetric conversion of 2-pyridones into the corresponding enantioenriched 2-piperidones.

Key words

asymmetric catalysis - hydrogenation - NHC - piperidone - pyridone

• References and Notes


For reviews on the hydrogenation of aromatic compounds, see:
• 1a Dyson PJ. Dalton Trans. 2003; 2964
• 1b Glorius F. Org. Biomol. Chem. 2005; 3: 4171
• 1c Zhou Y.-G. Acc. Chem. Res. 2007; 40: 1357
• 1d Kuwano R. Heterocycles 2008; 76: 909
• 1e Wang D.-S, Chen Q.-A, Lu S.-M, Zhou Y.-G. Chem. Rev. 2012; 112: 2557
• 1f Yu Z, Jin W, Jiang Q. Angew. Chem. Int. Ed. 2012; 51: 6060
• 1g Zhao D, Glorius F. Angew. Chem. Int. Ed. 2013; 52: 9616

For selected examples of asymmetric hydrogenation of quinolines, see:
• 2a Wang W.-B, Lu S.-M, Yang P.-Y, Han X.-W, Zhou Y.-G. J. Am. Chem. Soc. 2003; 125: 10536
• 2b Rueping M, Antonchick AP, Theissmann T. Angew. Chem. Int. Ed. 2006; 45: 3683
• 2c Zhou H.-F, Li Z.-W, Wang Z.-J, Wang T.-L, Xu L.-J, He Y.-M, Fan Q.-H, Pan J, Gu L.-Q, Chan AS. C. Angew. Chem. Int. Ed. 2008; 47: 8464
• 2d Guo Q.-S, Du D.-M, Xu J. Angew. Chem. Int. Ed. 2008; 47: 759
• 2e Wang T.-L, Zhuo L.-G, Li Z.-W, Chen F, Ding Z.-Y, He Y.-M, Fan Q.-H, Xiang J.-F, Yu Z.-X, Chan AS. C. J. Am. Chem. Soc. 2011; 133: 9878
• 2f Chen Q.-A, Gao K, Duan Y, Ye Z.-S, Shi L, Yang Y, Zhou Y.-G. J. Am. Chem. Soc. 2012; 134: 2442
• 2g Zhang D.-Y, Yu C.-B, Wang M.-C, Gao K, Zhou Y.-G. Tetrahedron Lett. 2012; 53: 2556
• 2h Maj AM, Suisse I, Méliet C, Hardouin C, Agbossou-Niedercorn F. Tetrahedron Lett. 2012; 53: 4747
• 2i Chen Z.-P, Ye Z.-S, Chen M.-W, Zhou Y.-G. Synthesis 2013; 45: 3239
• 2j Cai X.-F, Huang W.-X, Chen Z.-P, Zhou Y.-G. Chem. Commun. 2014; 50: 9588

For examples of asymmetric hydrogenation of isoquinolines, see:
• 3a Lu S.-M, Wang Y.-Q, Han X.-W, Zhou Y.-G. Angew. Chem. Int. Ed. 2006; 45: 2260
• 3b Shi L, Ye Z.-S, Cao L.-L, Guo R.-N, Hu Y, Zhou Y.-G. Angew. Chem. Int. Ed. 2012; 51: 8286
• 3c Iimuro A, Yamaji K, Kandula S, Nagano T, Kita Y, Mashima K. Angew. Chem. Int. Ed. 2013; 52: 2046
• 3d Ye Z.-S, Guo R.-N, Cai X.-F, Chen M.-W, Shi L, Zhou Y.-G. Angew. Chem. Int. Ed. 2013; 52: 3685
• 3e Kita Y, Yamaji K, Higashida K, Sathaiah K, Iimuro A, Mashima K. Chem. Eur. J. 2015; 21: 1915
• 4 Kita Y, Higashida K, Yamaji K, Iimuro A, Mashima K. Chem. Commun. 2015; 51: 4380

For selected examples of asymmetric hydrogenation of quinoxalines, see:
• 5a Murata S, Sugimoto T, Matsuura S. Heterocycles 1987; 26: 763
• 5b Bianchini C, Barbaro P, Scapacci G, Farnetti E, Graziani M. Organometallics 1998; 17: 3308
• 5c Bianchini C, Barbaro P, Scapacci G. J. Organomet. Chem. 2001; 621: 26
• 5d Qiu L, Kwong FY, Wu J, Lam WH, Chan S, Yu W.-Y, Li Y.-M, Guo R, Zhou Z, Chan AS. C. J. Am. Chem. Soc. 2006; 128: 5955
• 5e Tang W, Xu L, Fan Q.-H, Wang J, Fan B, Zhou Z, Lam K.-H, Chan AS. C. Angew. Chem. Int. Ed. 2009; 48: 9135
• 5f Mršić N, Jerphagnon T, Minnaard AJ, Feringa BL, de Vries JG. Adv. Synth. Catal. 2009; 351: 2549
• 5g Rueping M, Tato F, Schoepke FR. Chem. Eur. J. 2010; 16: 2688
• 5h Cartigny D, Nagano T, Ayad T, Genêt JP, Ohshima T, Mashima K, Ratovelomanana-Vidal V. Adv. Synth. Catal. 2010; 352: 1886
• 5i Wang D.-W, Wang D.-S, Chen Q.-A, Zhou Y.-G. Chem. Eur. J. 2010; 16: 1133
• 5j Chen Q.-A, Wang D.-S, Zhou Y.-G, Duan Y, Fan H.-J, Yang Y, Zhang Z. J. Am. Chem. Soc. 2011; 133: 6126
• 5k Cartigny D, Berhal F, Nagano T, Phanasavath P, Ayad T, Genêt P, Ohshima T, Mashima K, Ratovelomanana-Vidal V. J. Org. Chem. 2012; 77: 4544

For selected examples of hydrogenation of pyridines, see:
• 6a Glorius F, Spielkamp N, Holle S, Goddard R, Lehmann CW. Angew. Chem. Int. Ed. 2004; 43: 2850
• 6b Ye Z.-S, Chen M.-W, Chen Q.-A, Shi L, Duan Y, Zhou Y.-G. Angew. Chem. Int. Ed. 2012; 51: 10181

For recent examples of asymmetric hydrogenation of indoles/pyrroles, see:
• 7a Kuwano R, Sato K, Kurokawa T, Karube D, Ito Y. J. Am. Chem. Soc. 2000; 122: 7614
• 7b Kuwano R, Kaneda K, Ito T, Sato K, Kurokawa T, Ito Y. Org. Lett. 2004; 6: 2213
• 7c Kuwano R, Kashiwabara M. Org. Lett. 2006; 8: 2653
• 7d Kuwano R, Kashiwabara M, Ohsumi M, Kusano H. J. Am. Chem. Soc. 2008; 130: 808
• 7e Mršić N, Jerphagnon T, Minnaard AJ, Feringa BL, de Vries JG. Tetrahedron: Asymmetry 2010; 21: 7
• 7f Baeza A, Pfaltz A. Chem. Eur. J. 2010; 16: 2036
• 7g Wang D.-S, Chen Q.-A, Li W, Yu C.-B, Zhou Y.-G, Zhang X. J. Am. Chem. Soc. 2010; 132: 8909
• 7h Wang D.-S, Tang J, Zhou Y.-G, Chen M.-W, Duan Y, Jiang G.-F. Chem. Sci. 2011; 2: 803
• 7i Duan Y, Chen M.-W, Ye Z.-S, Wang D.-S, Chen Q.-A, Zhou Y.-G. Chem. Eur. J. 2011; 17: 7193
• 7j Wang D.-S, Ye Z.-S, Chen Q.-A, Zhou Y.-G, Yu C.-B, Fan H.-J, Duan Y. J. Am. Chem. Soc. 2011; 133: 8866
• 7k Duan Y, Chen M.-W, Chen Q.-A, Yu C.-B, Zhou Y.-G. Org. Biomol. Chem. 2012; 10: 1235
• 7l Duan Y, Li L, Chen M.-W, Yu C.-B, Fan H.-J, Zhou Y.-G. J. Am. Chem. Soc. 2014; 136: 7688
• 8 Wang T, Chen F, Qin J, He Y.-M, Fan Q.-H. Angew. Chem. Int. Ed. 2013; 52: 7172

For selected examples of hydrogenation of (benzo)thiophenes, see:
• 9a Bianchini C, Meli A. Acc. Chem. Res. 1998; 31: 109
• 9b Borowski AF, Sabo-Etienne S, Donnadieu B, Chaudret B. Organometallics 2003; 22: 4803
• 9c Urban S, Beiring B, Ortega N, Paul D, Glorius F. J. Am. Chem. Soc. 2012; 134: 15241

For selected examples of hydrogenation of (benzo)furans, see:
• 10a Ohta T, Miyake T, Seido N, Kumobayashi H, Takaya H. J. Org. Chem. 1995; 60: 357
• 10b Studer M, Wedemeyer-Exl C, Spindler F, Blaser H.-U. Monatsh. Chem. 2000; 131: 1335
• 10c Maris M, Huck W.-R, Mallat T, Baiker A. J. Catal. 2003; 219: 52
• 10d Kaiser S, Smidt SP, Pfaltz A. Angew. Chem. Int. Ed. 2006; 45: 5194
• 10e Feiertag P, Albert M, Nettekoven U, Spindler F. Org. Lett. 2006; 8: 4133
• 10f Ortega N, Urban S, Beiring B, Glorius F. Angew. Chem. Int. Ed. 2012; 51: 1710
• 10g Ortega N, Beiring B, Urban S, Glorius F. Tetrahedron 2012; 68: 5185
• 10h Wysocki J, Ortega N, Glorius F. Angew. Chem. Int. Ed. 2014; 53: 8751
• 10i Pauli L, Tannert R, Scheil R, Pfaltz A. Chem. Eur. J. 2015; 21: 1482
• 11 Ortega N, Tang D.-TD, Urban S, Zhao D, Glorius F. Angew. Chem. Int. Ed. 2013; 52: 9500
• 12 Zhang J, Chen F, He Y.-M, Fan Q.-H. Angew. Chem. Int. Ed. 2015; 54: 4622

For the asymmetric arene hydrogenation, see:
• 13a Urban S, Ortega N, Glorius F. Angew. Chem. Int. Ed. 2011; 50: 3803
• 13b Kuwano R, Morioka R, Kashiwabara M, Kameyama N. Angew. Chem. Int. Ed. 2012; 51: 4136

Selected examples of heterogeneous hydrogenation reactions of 2-pyridones:
• 14a Hartmann RW, Reichert M, Göhring S. Eur. J. Med. Chem. 1994; 29: 807
• 14b Hartmann RW, Reichert M. Arch. Pharm. 2000; 333: 145
• 14c Padwa A, Heidelbaugh TM, Kuethe JT. J. Org. Chem. 2000; 65: 2368
• 15 Zhao D, Beiring B, Glorius F. Angew. Chem. Int. Ed. 2013; 52: 8454
• 16 General Procedure for the Asymmetric Hydrogenation In a glovebox, [Ru(2-Me-allyl)₂(cod)] (4.8 mg, 0.015 mmol), ­SINpEt·HBF₄ (14.5 mg, 0.031 mmol) and dry KOt-Bu (5.0 mg, 0.045 mmol) were placed in a flame-dried screw-capped Schlenk tube equipped with a magnetic stirring bar. The mixture was suspended in 0.5 mL of hexane and stirred at 70 °C for 16 h after which t-AmOH (0.5 mL) was added and stirred at r.t. for 1 h. The resulted mixture was transferred under argon to a glass vial containing a 2-pyridone (0.3 mmol) and a magnetic stirring bar. Any applied additive (0.3 mmol) was added at this point. The glass vial was placed in a 150 mL stainless-steel reactor, and the H₂ pressure was set at 120 bar. The hydrogenation reaction was performed at the indicated temperature for 24 h. The crude post-reaction mixture was filtered through a plug of silica using 5% MeOH in CH₂Cl₂ followed by flash column chromatography (5% MeOH in CH₂Cl₂). The enantiomeric ratio of all compounds was determined by chiral GC or HPLC. Compound 4a: ¹H NMR (300 MHz, CDCl₃): δ = 3.46 (h, J = 6.4 Hz, 1 H), 2.92 (s, 3 H), 2.37 (t, J = 6.5 Hz, 2 H), 1.99–1.78 (m, 2 H), 1.76–1.54 (m, 2 H), 1.23 (d, J = 6.5 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 170.45, 54.47, 33.05, 32.21, 30.25, 19.95, 17.86. ESI-MS: m/z calcd for [C₇H₁₃NONa]⁺: 150.0889; found: 150.0889. FTIR (ATR): 1620, 1447, 1397, 1335, 1308, 1246, 1184, 1138, 1099, 1053, 1026, 910, 853, 691, 648 cm^–1.