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Synthesis 2012; 44(15): 2295-2309
DOI: 10.1055/s-0031-1289788
review
© Georg Thieme Verlag Stuttgart · New York

NHCs in Asymmetric Organocatalysis: Recent Advances in Azolium Enolate Generation and Reactivity

James Douglas
a   EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, KY16 9ST, UK
,
Gwydion Churchill
b   AstraZeneca, Process R&D, Macclesfield, Cheshire, SK10 2NA, UK, Fax: +44(1334)463806   Email: ads10@st-andrews.ac.uk
,
Andrew D. Smith*
a   EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, KY16 9ST, UK
› Author Affiliations
Further Information

Publication History

Received: 17 April 2012

Accepted after revision: 03 May 2012

Publication Date:
13 July 2012 (online)

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Abstract

Organocatalysis represents a synthetic paradigm that has grown exponentially in popularity over the last decade, arguably becoming one of the most desired synthetic methods for the creation of enantiomerically enriched products. Within this field the use of N-heterocyclic carbenes (NHCs) has seen appreciable research activity with the realisation of many novel reaction types. This review provides a comprehensive account of recent advances in the generation and reactivity of azolium enolates with exclusive focus on those processes rendered asymmetric through the use of chiral NHCs.

1 Introduction: NHCs in Organocatalysis

1.1 Azolium Enolates

2 Azolium Enolate Generation via Ketenes

2.1 Asymmetric Formal [2+2] Cycloadditions

2.2 Asymmetric Formal [3+2] Cycloadditions

2.3 Asymmetric Formal [4+2] Cycloadditions

2.4 Asymmetric Protonation and Halogenation

3 Azolium Enolate Generation via α-Functionalised Aldehydes

4 Azolium Enolate Generation via Enals

5 Activated Esters as Azolium Enolate Precursors

6 Conclusions and Outlook

Key words

N-heterocyclic carbene - azolium enolate - organocatalysis, ketene - α-functionalised aldehydes - Enals - activated esters
 

  • References

  • 1 Arduengo AJ, Harlow RL, Kline M. J. Am. Chem. Soc. 1991; 113: 361
  • 2 Igau A, Grutzmacher H, Baceiredo A, Bertrand G. J. Am. Chem. Soc. 1988; 110: 6463
  • 3 Wanzlick HW. Angew. Chem., Int. Ed. Engl. 1962; 1: 75
    Crossref
  • 4 Ukai T, Tanaka R, Dokawa T. J. Pharm. Soc. Jpn. 1943; 63: 296
    • 5a Breslow R. J. Am. Chem. Soc. 1958; 80: 3719
    • 5b Breslow R, Schmuck C. Tetrahedron Lett. 1996; 37: 8241
      Crossref
  • 6 Lapworth A. J. Chem. Soc., Trans. 1903; 83: 995
  • 7 Stetter H. Angew. Chem., Int. Ed. Engl. 1976; 15: 639
    Crossref
    • 8a Ryan SJ, Candish L, Lupton DW. J. Am. Chem. Soc. 2009; 131: 14176
    • 8b Candish L, Lupton DW. Org. Lett. 2010; 12: 4836
      Crossref
    • 8c De Sarkar S, Studer A. Angew. Chem. Int. Ed. 2010; 49: 9266
    • 8d Kaeobamrung J, Mahatthananchai J, Zheng P, Bode JW. J. Am. Chem. Soc. 2010; 132: 8810
    • 8e Zhu Z.-Q, Xiao J.-C. Adv. Synth. Catal. 2010; 352: 2455
    • 8f Biswas A, Sarkar SD, Fröhlich R, Studer A. Org. Lett. 2011; 13: 4966
      CrossrefPubMed
    • 8g Mahatthananchai J, Zheng P, Bode JW. Angew. Chem. Int. Ed. 2011; 50: 1673
      CrossrefPubMed
    • 8h Sun F-G, Sun L-H, Ye S. Adv. Synth. Catal. 2011; 353: 3134
    • 8i Wanner B, Mahatthananchai J, Bode JW. Org. Lett. 2011; 13: 5378
      CrossrefPubMed
    • 8j Biswas A, De Sarkar S, Tebben L, Studer A. Chem. Commun. 2012; 48: 5190
      CrossrefPubMed
    • 8k Mahatthananchai J, Kaeobamrung J, Bode JW. ACS Catal. 2012; 2: 494
      CrossrefPubMed
    • 8l Samanta RC, Maji B, De Sarkar S, Bergander K, Fröhlich R, Mück-Lichtenfeld C, Mayr H, Studer A. Angew. Chem. Int. Ed. 2012; 21: 5234
    • 8m Yao C, Wang D, Lu J, Li T, Jiao W, Yu C. Chem.−Eur. J. 2012; 18: 1914
    • 9a Enders D, Niemeier O, Henseler A. Chem. Rev. 2007; 107: 5606
    • 9b Marion N, Diez-Gonzalez S, Nolan SP. Angew. Chem. Int. Ed. 2007; 46: 2988
    • 9c Moore JL, Rovis T. Top. Curr. Chem. 2009; 291: 77
    • 10a Biju AT, Kuhl N, Glorius F. Acc. Chem. Res. 2011;
    • 10b Vora H, Rovis T. Aldrichimica Acta 2011; 44: 3
    • 11a Phillips E, Chan A, Scheidt K. Aldrichimica Acta 2009; 42: 55
    • 11b Nair V, Menon RS, Biju AT, Sinu CR, Paul RR, Jose A, Sreekumar V. Chem. Soc. Rev. 2011; 40: 5336
  • 12 Zhang Y.-R, He L, Wu X, Shao P.-L, Ye S. Org. Lett. 2007; 10: 277
  • 13 Duguet N, Campbell CD, Slawin AM. Z, Smith AD. Org. Biomol. Chem. 2008; 6: 1108
    • 14a Duguet N, Donaldson A, Leckie SM, Douglas J, Shapland P, Brown TB, Churchill G, Slawin AM. Z, Smith AD. Tetrahedron: Asymmetry 2010; 21: 582
      Crossref
    • 14b Duguet N, Donaldson A, Leckie SM, Kallstrom EA, Campbell CD, Shapland P, Brown TB, Slawin AM. Z, Smith AD. Tetrahedron: Asymmetry 2010; 21: 601
      Crossref
    • 15a Cannizzaro CE, Strassner T, Houk KN. J. Am. Chem. Soc. 2001; 123: 2668
      Crossref
    • 15b Cannizzaro CE, Houk KN. J. Am. Chem. Soc. 2004; 126: 10992
      Crossref
  • 16 Tang K, Wang J, Hou Q, Cheng X, Liu Y. Tetrahedron: Asymmetry 2011; 22: 942
    Crossref
  • 17 He L, Lv H, Zhang Y.-R, Ye S. J. Org. Chem. 2008; 73: 8101
  • 18 Wang X.-N, Shao P.-L, Lv H, Ye S. Org. Lett. 2009; 11: 4029
  • 19 Wang X.-N, Zhang Y.-Y, Ye S. Adv. Synth. Catal. 2010; 352: 1892
  • 20 Huang X.-L, Chen X.-Y, Ye S. J. Org. Chem. 2009; 74: 7585
  • 21 Wang T, Huang X.-L, Ye S. Org. Biomol. Chem. 2010; 8: 5007
  • 22 Jian T.-Y, He L, Tang C, Ye S. Angew. Chem. Int. Ed. 2011; 50: 9104
    • 23a Beecken H, Korte F. Tetrahedron 1962; 18: 1527
      Crossref
    • 23b Jäger U, Schwab M, Sundermeyer W. Chem. Ber. 1986; 119: 1127
      Crossref
  • 24 Lv H, Zhang Y.-R, Huang X.-L, Ye S. Adv. Synth. Catal. 2008; 350: 2715
    Crossref
  • 25 Wang X.-N, Shen L.-T, Ye S. Org. Lett. 2011; 13: 6382
    CrossrefPubMed
  • 26 Wang X.-N, Shen L.-T, Ye S. Chem. Commun. 2011; 47: 8388
    CrossrefPubMed
  • 27 Shao P.-L, Chen X.-Y, Ye S. Angew. Chem. Int. Ed. 2010; 49: 8412
  • 28 Huang X.-L, He L, Shao P.-L, Ye S. Angew. Chem. Int. Ed. 2009; 48: 192
  • 29 Zhang Y.-R, Lv H, Zhou D, Ye S. Chem.–Eur. J. 2008; 14: 8473
  • 30 Lv H, Chen X.-Y, Sun L.-h, Ye S. J. Org. Chem. 2010; 75: 6973
  • 31 Jian T.-Y, Shao P.-L, Ye S. Chem. Commun. 2011; 47: 2381
  • 32 Lv H, You L, Ye S. Adv. Synth. Catal. 2009; 351: 2822
  • 33 Shao P.-L, Chen X.-Y, Sun L.-H, Ye S. Tetrahedron Lett. 2010; 51: 2316
    Crossref
  • 34 Shen L.-T, Shao P.-L, Ye S. Adv. Synth. Catal. 2011; 353: 1943
  • 35 Wang X.-N, Lv H, Huang X.-L, Ye S. Org. Biomol. Chem. 2009; 7: 346
  • 36 Concellón C, Duguet N, Smith AD. Adv. Synth. Catal. 2009; 351: 3001
    Crossref
  • 37 Douglas J, Ling KB, Concellón C, Churchill G, Slawin AM. Z, Smith AD. Eur. J. Org. Chem. 2010; 5863
  • 38 Vora HU, Wheeler P, Rovis T. Adv. Synth. Catal. 2012; 354: 1617
    CrossrefPubMed
    • 39a Chow KY.-K, Bode JW. J. Am. Chem. Soc. 2004; 126: 8126
    • 39b Reynolds NT, Read de Alaniz J, Rovis T. J. Am. Chem. Soc. 2004; 126: 9518
    • 39c Chan A, Scheidt KA. Org. Lett. 2005; 7: 905
    • 39d Sohn SS, Bode JW. Org. Lett. 2005; 7: 3873
    • 39e Zeitler K. Angew. Chem. Int. Ed. 2005; 44: 7506
      CrossrefPubMed
    • 39f Ling KB, Smith AD. Chem. Commun. 2011; 47: 373
  • 40 Mahatthananchai J, Bode JW. Chem. Sci. 2012; 3: 192
  • 41 Reynolds NT, Rovis T. J. Am. Chem. Soc. 2005; 127: 16406
  • 42 Vora HU, Rovis T. J. Am. Chem. Soc. 2010; 132: 2860
    Crossref
  • 43 He M, Uc GJ, Bode JW. J. Am. Chem. Soc. 2006; 128: 15088
  • 44 He M, Beahm BJ, Bode JW. Org. Lett. 2008; 10: 3817
  • 45 Hayashi Y, Itoh T, Aratake S, Ishikawa H. Angew. Chem. Int. Ed. 2008; 47: 2082
    CrossrefPubMed
  • 46 Kobayashi S, Kinoshita T, Uehara H, Sudo T, Ryu I. Org. Lett. 2009; 11: 3934
    Crossref
  • 47 Kawanaka Y, Phillips EM, Scheidt KA. J. Am. Chem. Soc. 2009; 131: 18028
  • 48 He M, Struble JR, Bode JW. J. Am. Chem. Soc. 2006; 128: 8418
  • 49 Kaeobamrung J, Kozlowski MC, Bode JW. Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 20661
    CrossrefPubMed
  • 50 Fang X, Chen X, Chi YR. Org. Lett. 2011; 13: 4708
    CrossrefPubMed
  • 51 Wadamoto M, Phillips EM, Reynolds TE, Scheidt KA. J. Am. Chem. Soc. 2007; 129: 10098
    CrossrefPubMed
  • 52 Phillips EM, Roberts JM, Scheidt KA. Org. Lett. 2010; 12: 2830
  • 53 Phillips EM, Wadamoto M, Chan A, Scheidt KA. Angew. Chem. Int. Ed. 2007; 46: 3107
    CrossrefPubMed
  • 54 Li Y, Wang X.-Q, Zheng C, You S.-L. Chem. Commun. 2009; 5823
  • 55 Lv H, Mo J, Fang X, Chi YR. Org. Lett. 2011; 13: 5366
    CrossrefPubMed
  • 56 Hao L, Du Y, Chen X, Jiang H, Shao Y, Chi YR. Org. Lett. 2012; 14: 2154

      • For related processes using isothiourea-mediated catalysis to form ammonium enolates, see:
    • 57a Simal C, Lebl T, Slawin AM. Z, Smith AD. Angew. Chem. Int. Ed. 2012; 51: 3653
      CrossrefPubMed
    • 57b Belmessieri D, Morrill LC, Simal C, Slawin AM. Z, Smith AD. J. Am. Chem. Soc. 2011; 133: 2714
    • 57c Morrill LC, Lebl T, Slawin AM. Z, Smith AD. Chem. Sci. 2012; 3: 2088
      Crossref