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Synlett 2023; 34(01): 86-92
DOI: 10.1055/a-1929-0085
letter

Visible-Light-Driven α-Hydroxymethylation of Ketones in a Continuous-Flow Microreactor

Huinan Sun 
a   Department State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, P. R. of China
,
Jianing Li
a   Department State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, P. R. of China
,
Lei Yun
b   University of Leicester, Leicester, LE1 7RH, UK
,
Cunfei Ma
a   Department State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, P. R. of China
,
Zongyi Yu
a   Department State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, P. R. of China
,
Hongfei Zhu
a   Department State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, P. R. of China
,
Qingwei Meng∗
a   Department State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, P. R. of China
c   Ningbo Institute of Dalian University of Technology, Dalian University of Technology, Ningbo 315000, P. R. of China
,
Jingnan Zhao∗
a   Department State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, P. R. of China
› InstitutsangabenWe 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.
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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 - ketones

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1929-0085.
  • Supporting Information


Publikationsverlauf

Eingereicht: 18. Juli 2022

Angenommen nach Revision: 22. August 2022

Accepted Manuscript online:
22. August 2022

Artikel online veröffentlicht:
19. Oktober 2022

© 2022. Thieme. All rights reserved

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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.
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