The photocatalytic carbonylation reaction described in the paper provides a powerful method for direct C(sp3)–H activation of diverse alkanes, which enables regioselective installation of carbonyl moieties in simple and complex organic scaffolds. It benefits from the application of flow technology resulting not only in high gas-liquid mass transfer rates and fast reaction kinetics, but also in a scalable and safe process. Importantly, the method represents a promising pathway for upgrading light hydrocarbons at ambient temperature, thus expanding the toolkit for organic synthesis and opening the door to the use of these readily available feedstocks as coupling partners in the synthesis of complex organic molecules.

Abstract of the paper

Despite their abundance in organic molecules, considerable limitations still exist in synthetic methods that target the direct C–H functionalization at sp³-hybridized carbon atoms. This is even more the case for light alkanes, which bear some of the strongest C–H bonds known in Nature, requiring extreme activation conditions that are not tolerant to most organic molecules. To bypass these issues, synthetic chemists rely on prefunctionalized alkyl halides or organometallic coupling partners. However, new synthetic methods that target regioselectively C–H bonds in a variety of different organic scaffolds would be of great added value, not only for the late-stage functionalization of biologically active molecules but also for the catalytic upgrading of cheap and abundant hydrocarbon feedstocks. Here, we describe a general, mild and scalable protocol which enables the direct C(sp3)–H carbonylation of saturated hydrocarbons, including natural products and light alkanes, using photocatalytic hydrogen atom transfer (HAT) and gaseous carbon monoxide (CO). Flow technology was deemed crucial to enable high gas-liquid mass transfer rates and fast reaction kinetics, needed to outpace deleterious reaction pathways, but also to leverage a scalable and safe process.

Paper details

Fabian Raymenants, Tom Masson, Jesús Sanjosé-Orduna, Timothy Noël: Efficient C(sp3)–H Carbonylation of Light and Heavy Hydrocarbons with Carbon Monoxide via Hydrogen Atom Transfer Photocatalysis in Flow. Angew. Chem. Int. Ed. 2023, e202308563 DOI: 10.1002/anie.202308563

See also

Research group Flow Chemistry