Photocatalytic Hydroalkylation of Trifluoromethyl Alkenes with Gaseous Alkanes in Flow

 

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Abstract

The conversion of light alkanes into value-added products is becoming a field of high interest within the scientific community, as it avoids the use of prefunctionalized alkylating agents. However, the gaseous nature of these reagents, along with their intrinsic inertness due to their high bond-dissociation energies (99–105 kcal·mol^–1), have rendered traditional strategies ineffective or lacking in selectivity. The use of flow-chemistry technology has made a tremendous impact in this field, improving the efficiency of multiphasic processes through improved mass transfer and larger interfacial areas. In this work, we report a new flow-chemistry platform for the photocatalytic hydroalkylation of trifluoromethyl alkenes with both isobutane and n-butane. The methodology provides an efficient alternative for the rapid construction of trifluoromethyl alkanes, which are well-known and important bioisosteres of several functional groups.

Publikationsverlauf

Eingereicht: 28. März 2025

Angenommen nach Revision: 08. Mai 2025

Accepted Manuscript online:
08. Mai 2025

Artikel online veröffentlicht:
30. Juni 2025

© 2025. Thieme. All rights reserved

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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• 19 Photocatalytic Hydroalkylation of Electron-Deficient Alkenes; General Procedure: The corresponding trifluoromethyl alkene (0.2 mmol) and NaDT (24.4 mg, 0.01 mmol, 5 mol%) were added to an oven-dried vial equipped with a septum. Anhydrous MeCN (2 mL, 0.1 M) was added, and the solution was finally homogenized by sonication in an ultrasound bath. Anhydrous MeCN was pumped through using both pumps at 0.5 mL·min^–1 in order to purge the whole flow system (approximately 10 minutes). After that, the photoreactor was switched on along with the cooled gas generator, equilibrating the temperature of the system at 20–25 °C. The liquid phase was then combined with the gas stream through a T-mixer, with a liquid flow rate of 0.5 mL·min^–1 and a gas flow rate of 15 mL·min^–1 (30:1 gas-to-liquid ratio) for isobutane or 25 mL·min^–1 (50:1 gas-to-liquid ratio) for n-butane. No back pressure regulator was used for this step. After that, the whole reaction mixture was pressurized at 4.5 bar (gauge pressure). Finally, the reaction mixture was pumped over the UV-150 photoreactor (365 nm high-powered LEDs, 61 W output power, 10 mL, fluoropolymer capillary tube, 1/16′′ OD, 1.0 mm ID) at the corresponding flow rate. The obtained crude material was collected into a vial. The solution was filtered through a silica plug and the residue was washed with Et₂O (20 mL). Solvent was removed under reduced pressure, and the residue was finally purified by flash column chromatography, furnishing compounds 2–15.

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