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Synlett 2014; 25(07): 932-934
DOI: 10.1055/s-0033-1340919
letter
© Georg Thieme Verlag Stuttgart · New York

Improved Conditions for the Proline-Catalyzed Aldol Reaction of Acetone with Aliphatic Aldehydes

Alberto Martínez
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany   Fax: +49(208)3062999   Email: list@mpi-muelheim.mpg.de
,
Kristina Zumbansen
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany   Fax: +49(208)3062999   Email: list@mpi-muelheim.mpg.de
,
Arno Döhring
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany   Fax: +49(208)3062999   Email: list@mpi-muelheim.mpg.de
,
Manuel van Gemmeren
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany   Fax: +49(208)3062999   Email: list@mpi-muelheim.mpg.de
,
Benjamin List*
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany   Fax: +49(208)3062999   Email: list@mpi-muelheim.mpg.de
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Further Information

Publication History

Received: 04 February 2014

Accepted: 16 February 2014

Publication Date:
25 March 2014 (online)

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Dedicated to Max Malacria on the occasion of his 65th birthday

Abstract

The proline-catalyzed asymmetric aldol reaction between aliphatic aldehydes and acetone has, to date, remained underdeveloped. Challenges in controlling this reaction include avoiding undesired side reactions such as aldol condensation and self-aldolization. In recent years we have developed optimized conditions, which enable high yields and good to excellent enantioselectivities, and which are presented in this communication.

Key words

aldehydes - aldol reaction - asymmetric catalysis - organocatalysis - proline

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes

  • 1 Mahrwald R In Modern Aldol Reactions . Wiley-VCH; Weinheim: 2004
    CrossrefGoogle Scholar
    • 2a List B, Lerner RA, Barbas CF. III. J. Am. Chem. Soc. 2000; 122: 2395
      Crossref
    • 2b Notz W, List B. J. Am. Chem. Soc. 2000; 122: 7386
      Crossref
    • 2c List B, Pojarliev P, Castello C. Org. Lett. 2001; 3: 573
      CrossrefPubMed
  • 3 For the optimization of reaction conditions, see the Supporting Information.
  • 4 Between 84–87% of the total (S)-proline was reisolated and reused in different experiments, without loss catalytic activity.

      • For selected examples, see:
    • 5a Tang Z, Jiang F, Yu L.-T, Cui X, Gong L.-Z, Mi A.-Q, Jiang Y.-Z, Wu Y.-D. J. Am. Chem. Soc. 2003; 125: 5262
      Crossref
    • 5b Tang Z, Yang Z.-H, Chen X.-H, Cun L.-F, Mi A.-Q, Jiang Y.-Z, Gong L.-Z. J. Am. Chem. Soc. 2005; 127: 9285
      CrossrefPubMed
    • 5c Maa S, Zhang S, Duan W, Wang W. Bioorg. Med. Chem. Lett. 2009; 19: 3909
      Crossref
    • 6a Zumbansen K, Döhring A, List B. Adv. Synth. Catal. 2010; 352: 1135
      Crossref
    • 6b Abell S, Medina F, Tichit D, Pérez-Ramírez J, Cesteros Salagre P, Sueiras JE. Chem. Commun. 2005; 1453
    • 6c Yang S.-D, Wu L.-Y, Yan Z.-Y, Pan Z.-L, Liang Y.-M. J. Mol. Catal. A 2007; 268: 107
      Crossref
    • 6d Chi Y, Scroggins ST, Boz E, Fréchet JM. J. J. Am. Chem. Soc. 2008; 130: 17287
      Crossref
    • 7a Northrup AB, MacMillan DW. C. J. Am. Chem. Soc. 2002; 124: 6798
      CrossrefPubMed
    • 7b Cordova A. Tetrahedron Lett. 2004; 45: 3949
      Crossref