US scientists have developed a practical solvent-free process for conducting efficient catalytic carbon-carbon bond forming reactions using diazo compounds.

Chiral catalysts are used in the fine chemical and pharmaceutical industries for the production of single enantiomer products for the discovery and isolation of new drugs. The turnover number (TON) of a catalyst indicates how much of a substrate it can convert before being inactivated. Therefore, achieving high TON is highly desirable and allows smaller amounts of catalyst to be used, making the process cheaper as most commonly used metal complexes (Pd, Pt, Rh) are expensive.

Now, Huw Davies and colleagues at Emory University, Atlanta, have been able to use tiny amounts of catalyst to control the rate of carbenoid reactions, with 0.1 mg of catalyst able to catalyse a reaction involving 30 mg of material. Davies used diazo compounds, which as high energy substrates aids a rapid catalytic cycle.

'The success of this approach rests on the fact that we used a stabilized class of carbenoids' says Davies. '[This work] has a bit of a counter-culture approach with regards to the use of diazo compounds. Even though diazo compounds are known to have explosive properties they are still used in industrial processes to make pharmaceutical ingredients and the diazo group is a source of high energy which helps drive these catalytic reactions to completion' he adds.

When an active trapping agent was used, such as styrene, TON of 1.8 million were achieved at very low catalyst/substrate ratios. The use of donor-acceptor carbenoids, which are more stable than other classes of carbenoids, but still highly reactive also lead to less catalyst destruction and carbine dimerization, says Davies. Peter Maitlis, an expert in catalysis for chemical industry, at the University of Sheffield comments that the work is 'well executed and the authors have developed an elegant catalytic procedure'.

The team are now planning on developing new synthetic methods for the application of total synthesis and drug discovery and to evaluate how the low catalyst loadings can be applied to this type of chemistry.

Carl Saxton

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