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Synlett 2023; 34(01): 86-92
DOI: 10.1055/a-1929-0085
DOI: 10.1055/a-1929-0085
letter
Visible-Light-Driven α-Hydroxymethylation of Ketones in a Continuous-Flow Microreactor
We are grateful for financial support from the National Natural Science Foundation of China (U20A20143), Liaoning Province ‘Xingliao Talent Program’ Project (XLYC1902086), and the Dalian Science and Technology Innovation Fund (2019J11CY006). We thank the State Key Laboratory of Fine Chemicals and Advanced Science Center of Intelligent Materials and Chemical Engineering for their support.
Abstract
A visible-light-driven α-hydroxymethylation of ketones to generate the corresponding alcohols was achieved under continuous-flow conditions. MeOH was used as a green and renewable C1 source and solvent to enable the α-C(sp3)–H functionalization of ketones under irradiation by white LEDs. A flow microreactor operated under optimized conditions permitted this oxidation to proceed with a higher efficiency and a shortened reaction time of 215 minutes, which was improved ten times compared with the batch parallel reaction (36 h). Mechanism studies indicate the reaction proceeds by a radical pathway.
Key words
continuous flow - hydroxymethylation - photocatalysis - methanol - radical reactions - ketonesSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1929-0085.
- Supporting Information
Publication History
Received: 18 July 2022
Accepted after revision: 22 August 2022
Accepted Manuscript online:
22 August 2022
Article published online:
19 October 2022
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- 19 Batch Photocatalytic α-Hydroxymethylation of Priopiophenone (1a) Propiophenone (1a; 40.3 mg, 0.3 mmol), rose bengal (15.3 mg, 5 mol%), K2CO3 (41.5 mg, 1.0 equiv), MeOH (1 mL), and H2O (0.3 mL) were added to a 10 mL quartz tube. The mixture was stirred at rt and irradiated by a 7 W white LED under ambient air for 36 h. When the reaction was complete (TLC), the solution was concentrated under reduced pressure, and the mixture was purified by column chromatography [silica gel, PE–EtOAc (5:1)] to afford pure product 2a.
- 20 Photocatalytic α-Hydroxymethylation of Priopiophenone (1a) in a Microreactor A solution of propiophenone (1a; 0.1342 g, 1 mmol), rose bengal (0.3053 g, 30 mol%), and K2CO3 (0.1382 g, 1.0 equiv) in MeOH (10 mL) and H2O (3 mL) was delivered by an HPLC pump at 2 mL min–1 and the air flow was set to 12 mL min–1 with the mass-flow controller. Both fluids were conveyed to the continuous-flow photoreactor through per(fluoroalkoxyalkane) tubing (ID = 1.5 mm). Mixing and irradiation (6000 K white LED, 45 W) occurred along the entire reactor channel (10 mL internal volume) under 3 barg of pressure. After completion of the reaction (TLC), the solution was concentrated under reduced pressure and the residue was purified by column chromatography [silica gel, PE–EtOAc (5:1)] to afford pure product 2a. 1-(3-Hydroxy-2-methylphenyl)propan-1-one (2a) Colorless oil; yield: 0.103 g (63%). 1H NMR (600 MHz, CDCl3): δ = 7.96 (d, J = 7.2 Hz, 2 H), 7.57 (t, J = 7.2 Hz, 1 H), 7.47 (t, J = 7.2 Hz, 2 H), 3.93 (dd, J = 10.8, 7.2 Hz, 1 H), 3.80 (dd, J = 10.8, 4.2 Hz, 1 H), 3.70–3.62 (m, 1 H), 2.22 (s, 1 H), 1.23 (d, J = 7.2 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 204.4, 136.1, 133.3, 128.7, 128.4, 64.5, 42.9, 14.6.