Benzylic C−H acylation by cooperative NHC and photoredox catalysis

Methods that enable site selective acylation of sp3 C-H bonds in complex organic molecules are not well explored, particularly if compared with analogous transformations of aromatic and vinylic sp2 C-H bonds. We report herein a direct acylation of benzylic C-H bonds by merging N-heterocyclic carbene (NHC) and photoredox catalysis. The method allows the preparation of a diverse range of benzylic ketones with good functional group tolerance under mild conditions. The reaction can be used to install acyl groups on highly functionalized natural product derived compounds and the C-H functionalization works with excellent site selectivity. The combination of NHC and photoredox catalysis offers options in preparing benzyl aryl ketones.

Series spectrometer, signal intensities are categorized in strong (s), middle (m) and weak (w).

General procedure for the benzylic C-H acylation
To a Schlenk tube were added carbene catalyst A (6.3 mg, 0.02 mmol), 4CzIPN (1.6 mg, 0.002 mmol) or [Ir(dF(CF 3 )ppy) 2 (dtbbpy)]PF 6 (2.2 mg, 0.002) and Cs 2 CO 3 (65.2 mg, 0.2 mmol). Then the reaction tube was evacuated and backfilled with argon two times. Subsequently, a benzylic component (0.10 mmol) and an acyl fluoride (0.40 mmol) (if solid, they should be added at the beginning) and CH 3 CN (0.6 mL) were added. The resulting mixture was degassed under vacuum two times and then the mixture was irradiated with blue LEDs at room temperature for 24 h. After that, the residue was purified by silica gel chromatography using a mixture of n-pentane and ethyl acetate or pentane and diethylether as an eluent to get the desired product. Each reaction was carried out twice and the average value was used as the final yield.
The aqueous layer was separated and back-extracted with diethylether. The combined organic phases were dried over MgSO 4 and the solvent was removed under reduced pressure. The crude product was purified via column chromatography (pentane/ethyl acetate = 10/1) and the desired product was obtained as a yellow liquid (511 mg, 61% yield). 1

3-Methylchroman (2t)
Step 1: following a reported procedure, 23  data are in accordance with those described in literature. 23 Step 2: following a reported procedure, 15
After purification by flash chromatography (n-pentane/ethyl acetate = 20/1), the desired compound was obtained as a light yellow solid (18.5 mg, 66% yield). 1  Spectroscopic data are in accordance with those described in literature. 32