Gas-liquid flow set up for Pd-catalyzed aminocarbonylation with CO generated from CO2, towards radiolabeling application

Abstract

Carbon monoxide (CO) is a very useful and reactive gas in organic chemistry, but it is highly toxic. Therefore, in situ generation remains highly desirable to avoid direct manipulation. Generating CO from CO₂ represents a double interest: in situ CO generation from a cheap and abundant source and accessible applications for radiolabeling with carbon 11, which comes out of the cyclotron as [11C]CO₂. In this context, we developed an efficient process for incorporating a carbon atom from carbon dioxide (CO₂) in an amide compound in less than 5 min thanks to flow chemistry. Indeed, we successfully transformed CO₂ into CO in a column reactor filled with a disilane reductant and cesium fluoride (CsF) catalyst, connected to a microreactor where the CO could be incorporated into an amide through palladium-catalyzed aminocarbonylation. Validation with [13C]CO₂ demonstrated the process's applicability to other carbon isotope. This entirely flow-based process was completed within 3 min, and therefore offers a rapid, efficient, and safe approach for PET radiotracer synthesis with carbon-11, aligning with green chemistry principles.

Graphical Abstract