Synthetic toolbox: Carbonylation

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Carbonylation

The development of efficient and environmentally benign methods for the synthesis of industrially relevant molecules is central to improving the green credentials of the pharmaceutical and fine chemicals industries.  In this respect, catalysis is a key chemistry for achieving this. Of the broad arrays of catalytic reactions, the functionalisation of hydrocarbon feedstocks into more complex molecules using carbonylation is key area of research.

Carbonylation is formal addition of C=O unit into a molecule and the most atom efficient route to this is by using carbon monoxide (CO). Carbonylation is one of the core industrial technologies for the conversion of bulk materials into products of value for example, olefins can be converted by carbonylation to a variety of products such as alcohols, aldehydes and carboxylic acid derivatives. It has also been employed for the efficient synthesis of amides.

Despite its position as a core transformation industrially, carbonylations are rarely used in the synthesis of complex pharmaceutical molecules.  Beller et al. have hypothesised that this may be due to a reluctance by the research communities to operate the high pressure equipment involved when running reaction involving gasses, though they note that a number of catalytic methods for carbonylations are carried out at ambient to low pressures. [1] 

 

  1. A. Brennführer, H. Neumann and M. Beller, Palladium-Catalyzed Carbonylation Reactions of Aryl Halides and Related Compounds, Angew. Chem. Int. Ed., 2009, 48, 4114-4133.