CC BY-ND-NC 4.0 · Synthesis 2019; 51(05): 1178-1184
DOI: 10.1055/s-0037-1610404
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An Asymmetric Organocatalytic Aldol Reaction of a Hydrophobic Aldehyde in Aqueous Medium Running in Flow Mode

Lukas Schober
a  Chair of Organic Chemistry I, Faculty of Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany   Email: harald.groeger@uni-bielefeld.de
,
Shahilan Ratnam
a  Chair of Organic Chemistry I, Faculty of Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany   Email: harald.groeger@uni-bielefeld.de
,
Yasunobu Yamashita
a  Chair of Organic Chemistry I, Faculty of Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany   Email: harald.groeger@uni-bielefeld.de
,
Niklas Adebar
a  Chair of Organic Chemistry I, Faculty of Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany   Email: harald.groeger@uni-bielefeld.de
,
Matthias Pieper
a  Chair of Organic Chemistry I, Faculty of Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany   Email: harald.groeger@uni-bielefeld.de
,
b  Department of Chemistry (Organic Chemistry), University of Cologne, Greinstrasse 4, 50939 Cologne, Germany
,
Volker Hessel
c  Micro Flow Chemistry & Process Technology, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands
,
a  Chair of Organic Chemistry I, Faculty of Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany   Email: harald.groeger@uni-bielefeld.de
› Author Affiliations
EU-Research Project ONE-FLOW (“Catalyst Cascade Reactions in ‘One-Flow’ within a Compartmentalized, Green-Solvent ‘Digital Synthesis Machinery’ – End-to-End Green Process Design for Pharmaceuticals”), Work programme: EU proposal 737266.
Further Information

Publication History

Received: 06 November 2018

Accepted: 09 November 2018

Publication Date:
07 January 2019 (online)


Dedicated to Professor Dr. Jürgen Martens on the occasion of his 70th birthday

Published as part of the 50 Years SYNTHESIS – Golden Anniversary Issue

Abstract

Reaction conditions have been identified to conduct a one-pot asymmetric organocatalytic aldol reaction with a hydrophobic substrate in aqueous medium via a process running in flow mode. By employing a mixture of water and 2-propanol, a hydrophobic aldehyde and 3.6 mol% of an organocatalyst, this microreactor process affords the desired aldol adduct with a conversion of 74% and an enantioselectivity of 89% after a reaction time of 60 minutes.

 
  • References

  • 1 Present address: School of Chemical Engineering, The University of Adelaide, Adelaide, South Australia 5005, Australia.

    • Reviews:
    • 2a Rudroff F, Mihovilovic MD, Gröger H, Snajdrova R, Iding H, Bornscheuer UT. Nat. Catal. 2018; 1: 12
    • 2b Schrittwieser JH, Velikogne S, Hall M, Kroutil W. Chem. Rev. 2018; 118: 270
    • 2c Gröger H, Hummel W. Curr. Opin. Chem. Biol. 2014; 19: 171
    • 2d Denard CA, Hartwig JF, Zhao H. ACS Catal. 2013; 3: 2856
    • 5a Rulli G, Duangdee N, Hummel W, Berkessel A, Gröger H. Eur. J. Org. Chem. 2017; 812
    • 5b Heidlindemann M, Rulli G, Berkessel A, Hummel W, Gröger H. ACS Catal. 2014; 4: 1099
    • 5c Rulli G, Duangdee N, Baer K, Hummel W, Berkessel A, Gröger H. Angew. Chem. Int. Ed. 2011; 50: 7944; Angew. Chem. 2011, 123, 8092
    • 5d Baer K, Kraußer M, Burda E, Hummel W, Berkessel A, Gröger H. Angew. Chem. Int. Ed. 2009; 48: 9355 , Angew. Chem. 2009, 121, 9519
    • 6a Raj M, Singh VK. Chem. Commun. 2009; 6687
    • 6b Raj M, Maya V, Ginotra SK, Singh VK. Org. Lett. 2006; 8: 4097
    • 6c Maya V, Raj M, Singh VK. Org. Lett. 2007; 9: 2593
    • 6d Raj M, Maya V, Singh VK. J. Org. Chem. 2009; 74: 4289
    • 7a Duangdee N, Harnying W, Rulli G, Neudörfl J.-M, Gröger H, Berkessel A. J. Am. Chem. Soc. 2012; 134: 11196
    • 7b For a continuous asymmetric aldol reaction in organic medium with a heterogenized organocatalyst, see: Rulli G, Fredriksen KA, Duangdee N, Bonge-Hansen T, Berkessel A, Gröger H. Synthesis 2013; 45: 2512
  • 8 For a practical one-pot procedure toward a multigram-scale synthesis of organocatalyst 2 (Singh’s catalyst), see: Berkessel A, Harnying W, Duangdee N, Neudörfl J.-M, Gröger H. Org. Proc. Res. Dev. 2012; 16: 123
  • 9 EU-Research Project ONE-FLOW (“Catalyst Cascade Reactions in ‘One-Flow’ within a Compartmentalized, Green-Solvent ‘Digital Synthesis Machinery’ – End-to-End Green Process Design for Pharmaceuticals”), Work programme: EU proposal 737266; see: one-flow.org (accessed Nov 28, 2018).