Replacing toxic heavy metals with hypervalent iodine could be music to the ears of synthetic chemists.

Japanese chemists have found a cleaner way to make carbon–nitrogen bonds by oxidation. This reaction has traditionally needed toxic metals like lead, thallium or mercury. Yasuyuki Kita and colleagues at Osaka University have now found a way to replace the metals with much safer hypervalent iodine reagents. The new reaction conditions are very mild, said Kita, so could be used to make complex pharmaceuticals and agrochemicals.

Hypervalent iodine compounds, while formally having more than the usual eight outer electrons, are actually electron-deficient at the iodine atom itself. When Kita mixed the reagent with a solution of nitrogen-containing substrates, the iodine regained its missing electrons by helping itself to some from the nitrogen. This triggered the nitrogen to react with a neighbouring carbon atom, forming the new carbon–nitrogen bond.

‘Kita’s clever choice of reagents and optimisation of reaction conditions are a great and promising step forward,’ said Thomas Wirth, an expert in hypervalent iodine chemistry at Cardiff University, UK.

Kita has discovered that, if a co-oxidant is added to the reaction mixture, the reaction works with catalytic amounts of the iodine reagent. This means that, every time the hypervalent iodine reacts with a molecule of substrate, it is then reconverted back to the reactive form by the co-oxidant. Kita has so far used mCPBA (meta-chloroperoxybenzoic acid) as the co-oxidant, but plans to look into other options.

‘Modification of the co-oxidant is essential to make the catalytic strategy more versatile and practical,’ said Kita. ‘Use of cost effective and environmentally friendly co-oxidants such as molecular oxygen and hydrogen peroxide is highly desirable,’ he said.