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. 2017 May 1;8(5):3576-3585.
doi: 10.1039/c7sc00138j. Epub 2017 Mar 8.

Efficient and selective hydrogenation of amides to alcohols and amines using a well-defined manganese-PNN pincer complex

Veronica Papa  1 , Jose R Cabrero-Antonino  1 , Elisabetta Alberico  1   2 , Anke Spanneberg  1 , Kathrin Junge  1 , Henrik Junge  1 , Matthias Beller  1
Affiliations

Efficient and selective hydrogenation of amides to alcohols and amines using a well-defined manganese-PNN pincer complex

Veronica Papa et al. Chem Sci. .

Abstract

Novel well-defined NNP and PNP manganese pincer complexes have been synthetized and fully characterized. The catalyst Mn-2 containing an imidazolyaminolphosphino ligand shows high activity and selectivity in the hydrogenation of a wide range of secondary and tertiary amides to the corresponding alcohols and amines, under relatively mild conditions. For the first time, more challenging substrates like primary aromatic amides including an actual herbicide can also be hydrogenated using this earth-abundant metal-based pincer catalyst.

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Figures

Scheme 1
Scheme 1. Possible reaction pathways for the hydrogenation of amides.
Scheme 2
Scheme 2. Hydrogenation of amides to alcohols and amines catalyzed by: (a) ruthenium (previous work), (b) iron (previous work) and (c) manganese (this work). a See ESI for other examples of Ru–pincer catalysts reported for this reaction (Scheme S1†).
Scheme 3
Scheme 3. Synthesis of pincer ligand (1) and manganese complexes (Mn-1, Mn-2 and Mn-3).
Fig. 1
Fig. 1. Molecular structure of manganese complex Mn-2 with thermal ellipsoids drawn at the 30% probability level. Hydrogen atoms other than H3 have been omitted for the sake of clarity.
Fig. 2
Fig. 2. Study of the solvent effect in the hydrogenation of benzanilide 2 to aniline 3 and benzyl alcohol 4 catalyzed by Mn-2 complex. Standard reaction conditions: benzanilide 2 (49.30 mg, 0.25 mmol), Mn-2 (1.78 mg, 0.00375 mmol, 1.5 mol%), KOtBu (2.13 mg, 0.019 mmol, 8 mol%), solvent (2 mL), 30 bar of H2, 120 °C over 16 h. Conversion of 2 and yields of 3 and 4 were calculated by GC using hexadecane as external standard.
Scheme 4
Scheme 4. Hydrogenation of primary amides to corresponding alcohols catalyzed by Mn-2 complex. Standard reaction conditions: amide (0.25 mmol), KOtBu (3 eq. to Mn), cyclohexane/t-amylOH (1.5/0.5) mixture (2 mL), 50 bar of H2 and 140 °C. Specific reaction conditions for benzamide: Mn-2 (5 mol%) over 48 h, for nicotinamide: Mn-2 (7 mol%) over 24 h, for p-(trifluoromethyl)benzamide and 4-methoxybenzamide: Mn-2 (5 mol%), over 24 h. Conversion of the amide and yields of the corresponding benzyl alcohols were calculated by GC using hexadecane as external standard.
Scheme 5
Scheme 5. Selective hydrogenation of diflufenican to the corresponding alcohol and amine catalyzed by Mn-2 complex. Reaction conditions: diflufenican (98.6 mg, 0.25 mmol), Mn-2 cat. (5.92 mg, 0.0125 mmol, 5 mol%), KOtBu (2.8 mg, 0.025 mmol, 10 mol%), cyclohexane (2 mL), 30 bar of H2, 130 °C over 16 h. aConversion of amide and yield of amine was calculated by GC using hexadecane as external standard. bThe yield was calculated by 1H NMR using 1,3,5-trimethoxybenzene as external standard.
Scheme 6
Scheme 6. Mn-catalyzed selective hydrogenations of benzanilide 2 and N-acetyl-1,2,3,4-tetrahydroquinoline in the presence of tert-butyl-N-methylcarbamate (a) and (c) or diphenyl urea (b) and (d). Standard reaction conditions: substrate (0.25 mmol each one), Mn-2 cat. (2.37 mg, 0.005 mmol, 2 mol%), KOtBu (2.8 mg, 0.025 mmol, 10 mol%), cyclohexane (2 mL), 30 bar of H2, 100 °C over 16 h. Conversion of the starting material and yield of the products were calculated by GC using hexadecane as external standard.
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References

    1. Roose P., Eller K., Henkes E., Rossbacher R. and Höke H., Ullmann's Encyclopedia of industrial Chemistry, Germany, 2000.
    2. Jessop P. G., The handbook of homogeneous hydrogenation, Germany, 2006.

    1. For selected examples of carboxylic acid derivatives hydrogenation, see:

    2. Werkmeister S., Junge K., Wendt B., Alberico E., Jiao H. J., Baumann W., Junge H., Gallou F., Beller M. Angew. Chem., Int. Ed. 2014;53:8722–8726. - PubMed
    3. vom Stein T., Meuresch M., Limper D., Schmitz M., Holscher M., Coetzee J., Cole-Hamilton D. J., Klankermayer J., Leitner W. J. Am. Chem. Soc. 2014;136:13217–13225. - PubMed
    4. Srimani D., Mukherjee A., Goldberg A. F. G., Leitus G., Diskin-Posner Y., Shimon L. J. W., Ben David Y., Milstein D. Angew. Chem., Int. Ed. 2015;54:12357–12360. - PubMed
    5. Cui X. J., Li Y. H., Topf C., Junge K., Beller M. Angew. Chem., Int. Ed. 2015;54:10596–10599. - PubMed
    6. Korstanje T. J., van der Vlugt J. I., Elsevier C. J., de Bruin B. Science. 2015;350:298–301. - PubMed
    7. Naruto M., Saito S. Nat. Commun. 2015;6:8140. - PMC - PubMed
    8. Cabrero-Antonino J. R., Sorribes I., Junge K., Beller M. Angew. Chem., Int. Ed. 2016;55:387–391. - PubMed

    1. For a general book about organic reductions, see: for selected examples, see: ; for a review about chemoselective reduction of carboxamides, see:

    2. Seyden-Penne J., Reductions by the Aumino- and Borohydrides in Organic Synthesis, Wiley, New York, 2nd edn, 1997, .
    3. Zhou S., Junge K., Addis D., Das S., Beller M. Angew. Chem., Int. Ed. 2009;48:9507–9510. - PubMed
    4. Das S., Addis D., Zhou S. L., Junge K., Beller M. J. Am. Chem. Soc. 2010;132:4971–4971. - PubMed
    5. Pelletier G., Bechara W. S., Charette A. B. J. Am. Chem. Soc. 2010;132:12817–12819. - PubMed
    6. Das S., Addis D., Junge K., Beller M. Chem.–Eur. J. 2011;17:12186–12192. - PubMed
    7. Cheng C., Brookhart M. J. Am. Chem. Soc. 2012;134:11304–11307. - PubMed
    8. Das S., Wendt B., Moller K., Junge K., Beller M. Angew. Chem., Int. Ed. 2012;51:1662–1666. - PubMed
    9. Dombray T., Helleu C., Darcel C., Sortais J. B. Adv. Synth. Catal. 2013;355:3358–3362.
    10. Park S., Brookhart M. J. Am. Chem. Soc. 2012;134:640–653. - PubMed
    11. Reeves J. T., Tan Z. L., Marsini M. A., Han Z. X. S., Xu Y. B., Reeves D. C., Lee H., Lu B. Z., Senanayakea C. H. Adv. Synth. Catal. 2013;355:47–52.
    12. Blondiaux E., Cantat T. Chem. Commun. 2014;50:9349–9352. - PubMed
    13. Lampland N. L., Hovey M., Mukherjee D., Sadow A. D. ACS Catal. 2015;5:4219–4226.
    14. Mukherjee D., Shirase S., Mashima K., Okuda J. Angew. Chem., Int. Ed. 2016;55:13326–13329. - PubMed
    15. Volkov A., Tinnis F., Stagbrand T., Trillo P., Adolfsson H. Chem. Soc. Rev. 2016;45:6685–6697. - PubMed
    1. Brown H. C., Narasimhan S., Choi Y. M. Synthesis. 1981:441–442.
    2. March J., Advanced Organic Chemistry, Wiley, New york, 4th edn, 1992.
    3. Werkmeister S., Junge K., Beller M. Org. Process Res. Dev. 2014;18:289–302.
    1. Dub P. A., Ikariya T. ACS Catal. 2012;2:1718–1741.
    2. Dodds D. L. and Cole-Hamilton D. J., in Sustainable Catalysis: Challenges and practices for the Pharmaceutical and Fine Chemical Industries, John Wiley and Sons, Hoboken, NJ, 2013.
    3. Smith A. M., Whyman R. Chem. Rev. 2014;114:5477–5510. - PubMed