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Chemoselectivity goes with the flow
17 March 2010
Japanese researchers have devised a flow microreactor to control the chemoselectivity of synthetic organic reactions.
Chemoselective control of organic reactions is crucial for the synthesis of natural products and pharmaceuticals. Existing methods of chemoselective control often involve the use of catalysts such as enzymes and metal complexes, which can be difficult to synthesise and often involve practical difficulties. Now, a team of scientists led by Mahito Atobe at the Tokyo Institute of Technology, Yokohama, have designed a micro-flow reactor that controls the chemoselectivity of a carbonyl allylation reaction between an allylic halide and an aldehyde.
Electrochemical carbonyl allylation can produce either a gamma or alpha-adducts depending on whether the aldehyde or allylic halide is reduced by the cathode. If the aldehyde has a higher reduction potential, the gamma-adduct is produced but if the reduction potential of the allyic halide is higher, the alpha-adduct is favoured. Atobe's microreactor controls the regioselectivity regardless of the reagents' reduction potentials.
The flow reactor contains the cathode on one side with the anode opposite and an inlet positioned on each side through which the reactants are introduced. As the microchannels in the reactor are so small, laminar flow of the solutions occur meaning that there is almost no mixing between the two parallel streams before they reach the electrodes. When the aldehyde solution flows through the top inlet on the same side as the cathode, it is reduced and then reacts with the allylic halide to give the alpha-adduct as the main product. But when the inlets are reversed, the allylic halide is reduced at the cathode and the gamma-adduct becomes the major product.
'This flow microreactor electrochemical system can serve as an effective method for chemoselective generation of unstable organic intermediates such as cations, anions, and radicals,' says Atobe. He also says that the system could be scaled up for pharmaceutical or industrial synthesis by increasing the number of microchannels. 'An increase in throughput in the electrochemical microfluidics is achieved by a numbering-up approach, rather than by scaling-up,' he adds.
Paul Watts, an expert in electrochemical organic synthesis at the University of Hull, UK, comments, 'this work very elegantly demonstrates that by conducting the electrochemical reaction within the micro flow reactor the selectivity of the reaction could be substantially enhanced when compared to batch reactions. But the most significant result is that the selectivity could be reversed by simply switching the reagent flows.'
The next step for the researchers is to improve the efficiency of this method and also investigate the applicability of the technology to other synthetic organic reactions.
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Link to journal article
Chemoselective reaction system using a two inlet micro-flow reactor: application to carbonyl allylation
Fumihiro Amemiya, Keishi Fuse, Toshio Fuchigami and Mahito Atobe, Chem. Commun., 2010, 46, 2730
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