Photocatalytic C–F alkylation; facile access to multifluorinated arenes

From the top down; access to complex multifluorinated arenes via multiple photocatalytic C–F substitutions.


Photocatalytic C-F Alkylation
General procedure B for the photocatalytic C-F Alkylation reaction (standard conditions) An NMR tube was charged with fluoroarenes (0.1 mmol, 1.0 equiv), alkene (0.6 mmol, 6.0 equiv or 0.48 mmol, 4.8 equiv), N,N-diisopropylethylamine (0.12 mmol, 1.2 equiv) fac-tris (2-phenyl pyridinato-C 2 , N) Iridium(III) (Ir(ppy)3) (0.25 mM, 1 mL in MeCN), sealed glass capillary containing C6D6 and was capped with NMR septum (Ace glass, part no. 9096-25). When reaction was run in greater than 0.1 mmol of fluoroarenes, more than one NMR tube was used to set up reaction and each NMR tube had 1 mL of reaction mixture. The reaction was degassed via Ar bubbling for 15 min at 0 °C (to avoid evaporation of N,N-diisopropylethylamine) and then placed in a light bath (vide supra) such that the lower portion of the tube was submerged under the water bath which was maintained at 45 o C. The reaction was monitored periodically by 19 F NMR. After the complete consumption of starting material, CH3CN was removed via rotavap. The residue was treated with deionized water (2 mL) and extracted with DCM (3 x 1 mL). The organic portions were combined and dried with anhydrous MgSO4. The crude product was concentrated in vacuo and purified by normal phase or reverse phase chromatography.

General procedure C for the photocatalytic hydrodefluorination reaction
The reaction procedure is the same as General procedure B, but if the reaction did not go for completion in 24 h, an additional 3 equiv. of N,N -diisopropylethylamine were added to the reaction. Then the reaction was redegassed and returned to the light bath. In some cases total 20-S8 25 equiv of N,N-diisopropylethylamine were used. After the complete consumption of starting material the reaction was treated to the same workup described for General procedure B.

General procedure D for the photocatalytic C-F alkylation followed hydrodefluorination reaction
The reaction procedure is the same as General procedure B, but after the complete consumption of starting material, the volatiles, including excess alkene, were removed via rotavap. Then the residue was redissolved in CH3CN (1 mL). This solution was transferred to an NMR tube containing N,N-diisopropylethylamine (0.3 mmol, 3 equiv), a sealed glass (C6D6) capillary and was capped with NMR septum, and degassed and resubjected to reaction conditions and workup as described above.

General procedure E for the photocatalytic hydrodefluorination reaction (higher catalyst loading)
The reaction procedure is the same as General procedure B, except that the solution of photocatalyst was twice the concentration, tris(2-phenyl pyridinato-C 2 , N) Iridium(III) (Ir(ppy)3) (0.5 mM, 1 mL in MeCN). The reaction setup and workup followed that described above. The reaction was monitored periodically by 19 F NMR. If the reaction did not go for completion in 24 h, an additional 3 equiv of N,N -diisopropylethylamine was added, degassed and reaction continued. Eventually, a total of 20-25 equiv of N,N-diisopropylethylamine was used. If after the addition of amine the reaction did not resume ( 19 F NMR) additional catalyst (0.7 or 0.8 mol%) was added and the solution again degassed. After the complete consumption of starting material, the reaction was worked up as previously described.
Note: the stereochemical assignment was made on the basis of coupling constant value that matched with the literature 8 value of this bicyclic system.