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Synlett 2015; 26(11): 1557-1562
DOI: 10.1055/s-0034-1378703
letter
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Homogeneous Hydrogenation of 2-Pyridones

Jędrzej Wysocki
a   Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstr. 40, 48149 Münster, Germany   Email: glorius@uni-muenster.de
b   NRW Graduate School of Chemistry, Wilhelm-Klemm-Str. 10, 48149 Münster, Germany
,
Christoph Schlepphorst
a   Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstr. 40, 48149 Münster, Germany   Email: glorius@uni-muenster.de
,
Frank Glorius*
a   Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstr. 40, 48149 Münster, Germany   Email: glorius@uni-muenster.de
› Author Affiliations
Further Information

Publication History

Received: 10 March 2015

Accepted: 15 April 2015

Publication Date:
11 May 2015 (online)

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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

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1378703.
  • Supporting Information
 

  • References and Notes


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  • 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.