Sep 04, 2008 |
Two catalysts better than one
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(Nanowerk News) US researchers have cracked a long standing problem in chemical synthesis - the catalytic alpha-alkylation of aldehydes - by combining two catalysts in one pot. The reaction is the first to combine a transition metal catalyst with an organocatalyst, and offers a simple route to compounds that have previously been out of reach, the researchers say ("Merging Photoredox Catalysis with Organocatalysis: The Direct Asymmetric Alkylation of Aldehydes").
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The reaction relies on the interplay between both catalysts to generate two reactive compounds - an activated aldehyde and alkyl radical - that combine to form the product. Coupling aldehydes to a range of reaction partners, while controlling the product stereochemistry to give a single enantiomer, is a long standing aim of synthetic chemists - but had proven elusive, says David MacMillan, who led the research at Princeton. The new reaction gives good conversion rates, but most importantly, gives complete stereochemical control of product.
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The organocatalyst had been used previously by the Princeton group to activate aldehydes. But, despite activation, the aldehyde would only react with a narrow range of highly reactive partners. Adding the inorganic catalyst - a photoactive ruthenium complex - solved this problem, generating a highly reactive alkyl radical in situ that readily attacked the activated aldehyde.
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The dual catalytic cycles. (Image: Science)
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The photoactive inorganic ruthenium catalyst that the researchers chose is commonly used to mimic the processes of photosynthesis and operates through a single electron transfer process. However, whereas the light-activated catalysts typically used in synthesis require a powerful UV lamp, a standard light bulb was enough to activate the ruthenium catalyst, which could both pull apart the carbon-halogen bond to form the radical species and reduce the reaction intermediate to generate the desired product.
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'To my knowledge, no-one has taken photoredox catalysis and applied it to organic syntheses' says MacMillan. 'What is amazing is that the light from a standard fume hood is enough to get the reaction to go.'
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'Photochemistry usually requires specialist equipment, including a high energy radiation source.' says Matthew Gaunt of the University of Cambridge, UK. 'This system, requiring only the energy from a standard light bulb, makes the process instantly accessible to any synthetic chemist.'
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The general chemistry represented could be applied to other organic transformations, say the researchers. Equally, with it requiring such a low energy light source, it has the potential to be scaled-up far beyond the two gram scale that has so far been achieved.
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'This is a transformation I consider a "dream reaction",' says Benjamin List, a leader in the field of organocatalysis at the Max Planck Institute in Germany. 'This is clearly a reaction of great promise for natural product synthesis and the production of pharmaceuticals.'
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