• Yinli WangEmail author
Part of the Springer Theses book series (Springer Theses)


N-Heterocyclic carbene (NHC) has been well known as one of the most powerful organocatalysts for promoting a wide range of transformations. In this chapter, the Umpolung ability of NHC to convert the electrophilic carbonyl group to the nucleophilic acyl anion or homoenolate intermediates will be discuss. Another unique character of NHC, generation of acyl azolium intermediates, will also be described here.


N-heterocyclic carbene Umpolung Acylazolium 


  1. 1.
    Bourissou D, Guerret O, Gabbaï FP, Bertrand G (2000) Stable Carbenes. Chem Rev 100:39-92CrossRefGoogle Scholar
  2. 2.
    Bauschlicher CW, Shavitt I (1978) Accurate ab initio calculations on the singlet-triplet separation in methylene. J Am Chem Soc 100:739–743CrossRefGoogle Scholar
  3. 3.
    (a) Wanzlick H-W, Schönherr H-J (1968) Direct Synthesis of a Mercury Salt‐Carbene Complex. Angew Chem Int Ed 7:141–142. (b) Öfele K (1968) 1,3-Dimethyl-4-imidazolinyliden-(2)-pentacarbonylchrom ein neuer übergangsmetall-carben-komplex. J Organomet Chem 12:42–43Google Scholar
  4. 4.
    Arduengo AJ, Harlow RL, Kline M (1991) A stable crystalline carbene. J Am Chem Soc 113:361–363CrossRefGoogle Scholar
  5. 5.
    Herrmann WA, Elison M, Fischer J, Köcher C, Artus GRJ (1995) Metal Complexes of N‐Heterocyclic Carbenes—A New Structural Principle for Catalysts in Homogeneous Catalysis. Angew Chem Int Ed 34:2371–2374CrossRefGoogle Scholar
  6. 6.
    Díez-González S, Marion N, Nolan SP (2009) N-Heterocyclic Carbenes in Late Transition Metal Catalysis. Chem Rev 109:3612–3676Google Scholar
  7. 7.
    Sheehan JC, Hunneman DH (1966) Homogeneous Asymmetric Catalysis. J Am Chem Soc 88:3666–3667CrossRefGoogle Scholar
  8. 8.
    Herrmann WA, Goossen LJ, Köcher C, Artus GRJ (1996) Chiral Heterocylic Carbenes in Asymmetric Homogeneous Catalysis. Angew Chem Int Ed 35:2805–2807CrossRefGoogle Scholar
  9. 9.
    (a) Enders D, Breuer K, Runsink J, Teles JH (1996) The First Asymmetric Intramolecular Stetter Reaction. Helv Chim Act 79:1899–1902. (b) Enders D, Kallfass U (2002) An Efficient Nucleophilic Carbene Catalyst for the Asymmetric Benzoin Condensation. Angew Chem Int Ed 41:1743–1745Google Scholar
  10. 10.
    Knight RL, Leeper FJ (1998) Comparison of chiral thiazolium and triazolium salts as asymmetric catalysts for the benzoin condensation. J Chem Soc Perkin Trans 1:1891–1894Google Scholar
  11. 11.
    Kerr MS, Read de Alaniz J, Rovis T (2002) A Highly Enantioselective Catalytic Intramolecular Stetter Reaction. J Am Chem Soc 124:10298-10299CrossRefGoogle Scholar
  12. 12.
    Matsumoto Y, Tomioka K (2006) C2 Symmetric chiral N-heterocyclic carbene catalyst for asymmetric intramolecular Stetter reaction. Tetrahedron Lett 47:5843–5846CrossRefGoogle Scholar
  13. 13.
    (a) Seebach D (1979) Methods of Reactivity Umpolung. Angew Chem Int Ed 18:239-258. (b) Grobel BT, Seebach D (1977) Umpolung of the Reactivity of Carbonyl Compounds Through Sulfur-Containing Reagents. Synthesis 357–402. (c) Seebach D, Wilka E-M (1976) Alkylation of 2-Lithio-1,3-dithianes with Arenesulfonates of Primary Alcohols. Synlett 476–477. (d) Seebach D, Corey EJ (1975) Generation and synthetic applications of 2-lithio-1,3-dithianes. J Org Chem 40:231–237Google Scholar
  14. 14.
    Wöhler F, Liebig J (1832) Untersuchungen über das Radikal der Benzoesäure. Ann Der Pharm 3:249–282CrossRefGoogle Scholar
  15. 15.
    Ukai T, Tanaka R, Dokawa TJ (1943) Pharm Soc Jpn 63:296Google Scholar
  16. 16.
    Breslow R (1958) On the Mechanism of Thiamine Action. IV.1 Evidence from Studies on Model Systems. J Am Chem Soc 80:3719–3726CrossRefGoogle Scholar
  17. 17.
    For reviews on benzoin reaction, see: (a) Menon RS, Biju AT, Nair V (2016) Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions. Beilstein J Org Chem 12:444–461. (b) Enders D, Balensiefer T (2004) Nucleophilic Carbenes in Asymmetric Organocatalysis. Acc Chem Res 37:534–541Google Scholar
  18. 18.
    For reviews on Stetter reaction, see: (a) Yetra SR, Patra A, Biju AT (2015) Recent Advances in the N-Heterocyclic Carbene (NHC)-Organocatalyzed Stetter Reaction and Related Chemistry. Synthesis 1357–1378. (b) Read de Alaniz J, Rovis T (209) The Catalytic Asymmetric Intramolecular Stetter Reaction. Synlett 1189–1207. (c) Rovis T (2008) Development of Chiral Bicyclic Triazolium Salt Organic Catalysts: The Importance of the N-Aryl Substituent. Chem Lett 37:2–7. (d) Stetter H (1976) Catalyzed Addition of Aldehydes to Activated Double Bonds—A New Synthetic Approach. Angew Chem Int Ed 15:639–647. For a highlight, see (e) Christmann M (2005) New Developments in the Asymmetric Stetter Reaction. Angew Chem Int Ed 44:2632–2634Google Scholar
  19. 19.
    For review, see (a) Biju AT, Kuhl N, Glorius F (2011) Extending NHC-Catalysis: Coupling Aldehydes with Unconventional Reaction Partners. Acc Chem Res 44:1182–1195. For recent reports, see: (b) Janssen-Müller D, Fleige M, Schlüns D, Wollenburg M, Daniliuc CG, Neugebauer J, Glorius F (2016) NHC-Catalyzed Enantioselective Dearomatizing Hydroacylation of Benzofurans and Benzothiophenes for the Synthesis of Spirocycles. ACS Catal 6:5735–5739. (c) Janssen-Müller D, Schedler M, Fleige M, Daniliuc CG, Glorius F (2015) Enantioselective Intramolecular Hydroacylation of Unactivated Alkenes: An NHC‐Catalyzed Robust and Versatile Formation of Cyclic Chiral Ketones. Angew Chem Int Ed 54:12492–12496. (d) Schedler M, Wang D-S, Glorius F (2013) NHC‐Catalyzed Hydroacylation of Styrenes. Angew Chem Int Ed 52:2585–2589. (e) Liu F, Bugaut X, Schedler M, Frçhlich R, Glorius F (2011) Designing N‐Heterocyclic Carbenes: Simultaneous Enhancement of Reactivity and Enantioselectivity in the Asymmetric Hydroacylation of Cyclopropenes. Angew Chem Int Ed 50:12626–12630Google Scholar
  20. 20.
    Burstein C, Glorius F (2004) Organocatalyzed Conjugate Umpolung of α,β‐Unsaturated Aldehydes for the Synthesis of γ‐Butyrolactones. Angew Chem Int Ed 43:6205–6208CrossRefGoogle Scholar
  21. 21.
    Fischer CS, Smith W, Powell DA, Fu GC (2006) Challenge To Detect 1,4-Zwitterions Spectroscopically in a Ketene−Alkene Reaction. J Am Chem Soc 128:44–45Google Scholar
  22. 22.
    (a) Schedler M, Wurz NE, Daniliuc CG, Glorius F (2014) N-Heterocyclic Carbene Catalyzed Umpolung of Styrenes: Mechanistic Elucidation and Selective Tail-to-Tail Dimerization. Org Lett 16:3134–3137. (b) Matsuoka S, Ota Y, Washio A, Katada A, Ichioka K, Takagi K, Suzuki M (2011) Organocatalytic Tail-to-Tail Dimerization of Olefin: Umpolung of Methyl Methacrylate Mediated by N-Heterocyclic Carbene. Org Lett 13:3722–3725. (c) Biju AT, Padmanaban M, Wurz NE, Glorius F (2011) N‐Heterocyclic Carbene Catalyzed Umpolung of Michael Acceptors for Intermolecular Reactions. Angew Chem Int Ed 50:8412–8415Google Scholar
  23. 23.
    (a) Khaleeli N, Li R, Townsend CA (1999) Origin of the β-Lactam Carbons in Clavulanic Acid from an Unusual Thiamine Pyrophosphate-Mediated Reaction. J Am Chem Soc 121:9223-9224. (b) Merski M, Townsend CA (2007) Observation of an Acryloyl−Thiamin Diphosphate Adduct in the First Step of Clavulanic Acid Biosynthesis. J Am Chem Soc 129:15750–15751Google Scholar
  24. 24.
    Lienhard GEJ (1966) Kinetics and Mechanism of the Hydrolysis of 2-Acetyl-3,4-dimethylthiazolium Ion. J Am Chem Soc 88:5642–5649CrossRefGoogle Scholar
  25. 25.
    (a) Hudson RF, Wardill JE (1950) The mechanism of hydrolysis of acid chlorides. Part I. The effect of hydroxyl ions, temperature, and substituents on the rate of hydrolysis of benzoyl chloride. J Chem Soc 1729–1733. (b) Hudson RF, Moss CE (1962) The mechanism of hydrolysis of acid chlorides. Part IX. Acetyl chloride. J Chem Soc 5157–5163Google Scholar
  26. 26.
    Daigo K, Reed LJ (1962) Synthesis and Properties of 2-Acetyl-3,4-dimethylthiazolium Iodide. J Am Chem Soc 84:659–662CrossRefGoogle Scholar
  27. 27.
    (a) Chow KY-K, Bode JW (2004) Catalytic Generation of Activated Carboxylates:  Direct, Stereoselective Synthesis of β-Hydroxyesters from Epoxyaldehydes. J Am Chem Soc 126:8126–8127. (b) Reynolds NT, de Alaniz JR, Rovis T (2004) Conversion of α-Haloaldehydes into Acylating Agents by an Internal Redox Reaction Catalyzed by Nucleophilic Carbenes. J Am Chem Soc 126:9518–9519Google Scholar
  28. 28.
    De Sarkar S, Grimme S, Studer A (2010) NHC Catalyzed Oxidations of Aldehydes to Esters: Chemoselective Acylation of Alcohols in Presence of Amines. J Am Chem Soc 132:1190–1191Google Scholar
  29. 29.
    Kuwano S, Harada S, Oriez R, Yamada K (2012) Chemoselective conversion of α-unbranched aldehydes to amides, esters, and carboxylic acids by NHC-catalysis. Chem Commun 48:145–147CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Graduate School of Pharmaceutical SciencesKyoto UniversityKyotoJapan

Personalised recommendations