Ex-situ generation and synthetic utilization of bare trifluoromethyl anion in flow via rapid biphasic mixing.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36869027.
- Also identified by DOI 10.1038/s41467-022-35611-9 and PMC identifier 9984407.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Fluoroform (CF<sub>3</sub>H) is the simplest reagent for nucleophilic trifluoromethylation intermediated by trifluoromethyl anion (CF<sub>3</sub><sup>-</sup>). However, it has been well-known that CF<sub>3</sub><sup>-</sup> should be generated in presence of a stabilizer or reaction partner (in-situ method) due to its short lifetime, which results in the fundamental limitation on its synthetic utilization. We herein report a bare CF<sub>3</sub><sup>-</sup> can be ex-situ generated and directly used for the synthesis of diverse trifluoromethylated compounds in a devised flow dissolver for rapid biphasic mixing of gaseous CF<sub>3</sub>H and liquid reagents that was designed and structurally optimized by computational fluid dynamics (CFD). In flow, various substrates including multi-functional compounds were chemoselectively reacted with CF<sub>3</sub><sup>-</sup>, extending to the multi-gram-scale synthesis of valuable compounds by 1-hour operation of the integrated flow system.