The development of metal-catalysed methods to functionalize inert C–H bonds has become a dominant research theme in the past decade as an approach to efficient synthesis. However, the incorporation of carbon monoxide into such reactions to form valuable ketones has to date proved a challenge, despite its potential as a straightforward and green alternative to Friedel–Crafts reactions. Here we describe a new approach to palladium-catalysed C–H bond functionalization in which carbon monoxide is used to drive the generation of high-energy electrophiles. This offers a method to couple the useful features of metal-catalysed C–H functionalization (stable and available reagents) and electrophilic acylations (broad scope and selectivity), and synthesize ketones simply from aryl iodides, CO and arenes. Notably, the reaction proceeds in an intermolecular fashion, without directing groups and at very low palladium-catalyst loadings. Mechanistic studies show that the reaction proceeds through the catalytic build-up of potent aroyl triflate electrophiles.
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We thank Natural Sciences and Engineering Research Council of Canada, the Canadian Foundation for Innovation and the Centre for Green Chemistry and Catalysis (supported by Fonds de recherche du Québec – Nature et Technologies) for funding this research. We thank L. Kayser for the X-ray crystal structure of 3a and to S. Kelley for the X-ray crystal structure of 4b.
The authors declare no competing financial interests.
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Crystallographic data for compound 3a (CIF 657 kb)
Crystallographic data for compound 4b (CIF 4930 kb)
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Garrison Kinney, R., Tjutrins, J., Torres, G. et al. A general approach to intermolecular carbonylation of arene C–H bonds to ketones through catalytic aroyl triflate formation. Nature Chem 10, 193–199 (2018). https://doi.org/10.1038/nchem.2903
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