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Synlett 2009(15): 2382-2391  
DOI: 10.1055/s-0029-1217828
ACCOUNT
© Georg Thieme Verlag Stuttgart ˙ New York

Developing Continuous-Flow Microreactors as Tools for Synthetic Chemists

Karolin Geyera, Tomas Gustafssona,b, Peter H. Seeberger*a,c
a Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH) Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland
Fax: +41(44)6331235; e-Mail: seeberger@org.chem.ethz.ch;
b Medicinal Chemistry, AstraZeneca R&D, Mölndal, 43183 Mölndal, Sweden
c Max Planck Institute of Colloids and Interfaces, Department of Biomolecular Systems, Arnimallee 22, 14195 Berlin, Germany
e-Mail: peter.seeberger@mpikg.mpg.de;
Further Information

Publication History

Received 5 December 2008
Publication Date:
28 August 2009 (online)

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Abstract

Microfluidic devices are emerging as true alternatives to traditional batch processes, as evidenced by recent applications in important synthetic transformations. Besides biologically important oligomers such as β-peptides and oligosaccharides, pharmaceutically active substances have been the target of the most recent investigations. Furthermore, synthetic processes posing challenges to process chemists such as highly exothermic or explosive reactions and reactions that are difficult to control on large scale (such as radical transformations) have been of particular interest. This account briefly introduces the concepts of continuous-flow microreactors, and reviews our investigations on the application of microfluidic devices in synthetic transformations such as glycosylations, amide bond formations mediated by trimethylaluminum, radical-based transformations, and deoxyfluorinations.

1 Introduction

2 Classical Chemical Transformations

2.1 Proof-of-Principle Studies

2.2 Trimethylaluminum-Mediated Amide Bond Formations

2.3 Deoxyfluorinations with (Diethylamino)sulfur Trifluoride

3 Synthesis of Biopolymers

3.1 Synthesis of Carbohydrates

3.1.1 Glycosylation Reactions

3.1.2 Synthesis of Oligosaccharides

3.2 Synthesis of β-Peptides

4 Free-Radical-Based Reactions

4.1 Dehalogenations and Deoxygenations

4.2 Hydrosilylations

5 Conclusions

Key words

microreactors - continuous flow - oligosaccharides - β-peptides - fluorinations - amide bond formation - scale-up