Angew.Chem.Int.Ed.http://doi.org/f2qksb(2014)

Many reductants are available to chemists, but molecular hydrogen is one of the most common both in academic labs and in industry. Though storage and transport can be a difficulty, hydrogen typically exhibits high reactivity, is cost effective on scale and can give perfect atom economy. Hydrogen is typically produced by steam-reforming of natural gas. The final stage of this process is the water–gas shift reaction: carbon monoxide reacts with steam to generate carbon dioxide and hydrogen. The carbon monoxide is oxidized and is therefore an indirect reductant.

Now, Denis Chusov from the Russian Academy of Sciences and Benjamin List from the Max Plank Institute have taken this process one step further using carbon monoxide as a reductant without the addition of an extra hydrogen source. They chose to study a reductive amination — a widely used amine synthesis in which an amine and carbonyl react, followed by reduction of the resultant imine. Using carbon monoxide in combination with rhodium acetate catalyst for the reduction afforded good yields of product directly from amines and carbonyls. The methodology was applicable to a wide range of substrates including both aldehydes and ketones, and in cases where other reducible functionalities (such as cyano and nitro groups) were present. Both primary and secondary amines were tolerated.

Mechanistic studies showed that, contrary to expectations, the reduction did not involve the generation of molecular hydrogen from carbon monoxide and water liberated from the amine–carbonyl condensation. Indeed, replacing CO with hydrogen under otherwise identical reaction conditions resulted in significantly reduced yields. Similarly, the addition of extra water, which would have been expected to boost hydrogen production, instead decreased the rate of reductive amination — raising questions about the active reducing agent. The authors propose a mechanism in which the hemiaminal intermediate — from the initial amine–carbonyl reaction — transfers a hydroxyl group to an in situ-formed rhodium carbonyl. Loss of carbon dioxide from the resultant species gives a rhodium hydride, which can then reduce the coordinated iminium.