Asymmetric Organocatalytic Aldol Reaction in Water: Mechanistic Insights and Development of a Semi-Continuously Operating Process

Giuseppe Rulli; Kim A. Fredriksen; Nongnaphat Duangdee; Tore Bonge-Hansen; Albrecht Berkessel; Harald Gröger

doi:10.1055/s-0033-1338509

Synthesis, Inhaltsverzeichnis

Synthesis 2013; 45(18): 2512-2519
DOI: 10.1055/s-0033-1338509

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Asymmetric Organocatalytic Aldol Reaction in Water: Mechanistic Insights and Development of a Semi-Continuously Operating Process

Giuseppe Rulli

^aDepartment of Chemistry and Pharmacy, University of Erlangen-Nürnberg, Henkestraße 42, 91054 Erlangen, Germany

,

Kim A. Fredriksen

^bDepartment of Chemistry, University of Oslo, P. O. Box 1033 Blindern, 0315 Oslo, Norway

,

Nongnaphat Duangdee

^cDepartment of Chemistry, University of Cologne, Greinstr. 4, 50939 Cologne, Germany eMail: berkessel@uni-koeln.de

,

Tore Bonge-Hansen

^bDepartment of Chemistry, University of Oslo, P. O. Box 1033 Blindern, 0315 Oslo, Norway

,

Albrecht Berkessel*

^cDepartment of Chemistry, University of Cologne, Greinstr. 4, 50939 Cologne, Germany eMail: berkessel@uni-koeln.de

,

Harald Gröger*

^aDepartment of Chemistry and Pharmacy, University of Erlangen-Nürnberg, Henkestraße 42, 91054 Erlangen, Germany

^dFaculty of Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany Fax: +49(521)1066146 eMail: harald.groeger@uni-bielefeld.de

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Abstract

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Dedicated to Professor Dr. Jürgen Martens on the occasion of his 65th birthday

Abstract

A detailed study on the impact of the catalyst loading on conversion and enantioselectivity of the direct aldol reaction of an aldehyde and acetone in aqueous solvent with nonimmobilized and immobilized proline amide-based organocatalysts is described. Based on a polymer-supported catalyst, batch and semi-continuously operating processes, comprising recycling studies in the latter case, were investigated.

Key words

aldol reaction - catalysis - enantioselectivity - supported catalysis - polymers

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Referenzen

References

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9 The overall conversions decrease slightly by applying higher catalyst loadings (e.g., 1.0 mol%: 93%; 5.0 mol%: 87%). Although no detailed explanation is as yet available, this effect might be related (at least to some extent) to an increased formation of an inactive catalyst–substrate adduct in the case of reactions conducted at higher catalyst loading (for the formation of related adducts, see ref. 3d). The differences in the product-related conversions are primarily caused by the higher impact of the side-product formation (via dehydration of aldol product 4) in the case of the reactions conducted at higher catalyst loading.

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11 Because of the large amount of catalyst, the solvent is completely absorbed by the polymer, leading to the formation of a gel.
12 An example for the recycling of 2 in a batch reactor is given in the Supporting Information.

For recent applications of immobilized organocatalysts in continuous flow systems, see:

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14a Rulli, G.; Gröger, H., unpublished results.
14b For further information about the role of water as an essential component for an efficient organocatalytic aldol reaction, see ref. 2b and: Gruttadauria M, Giacalone F, Noto R. Adv. Synth. Catal. 2009; 351: 33

15 Li X, Li L, Tang Y, Zhong L, Cun L, Zhu J, Liao J, Deng J. J. Org. Chem. 2010; 75: 2981

Zusatzmaterial

Supporting Information