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

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
› Institutsangaben
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.

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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  • References and Notes

    • 1a Suau R, Nájera F, Rico R. Tetrahedron 1999; 55: 4019
    • 1b Reeves BM, Hepburn HB, Grozavu A, Lindsay-Scott PJ, Donohoe TJ. Angew. Chem. Int. Ed. 2019; 58: 15697
    • 1c Zhao S, Mankad NP. Angew. Chem. Int. Ed. 2018; 57: 5867
    • 1d Suau R, Nájera F, Rico R. Tetrahedron Lett. 1996; 37: 3575
    • 2a Sloan KB, Bodor N. Int. J. Pharm. (Amsterdam, Neth.) 1982; 12: 299
    • 2b Santos SS, Gonzaga RV, Scarim CB, Giarolla J, Primi MC, Chin CM, Ferreira EI. Front. Chem. (Lausanne, Switz.) 2022; 9: 734983 DOI: 10.3389/fchem.2021.734983.
    • 3a Biswas S, Dutta B, Mannodi-Kanakkithodi A, Clark R, Song W, Ramprasad R, Suib SL. Chem. Commun. 2017; 53: 11751
    • 3b Franco MS, Saba S, Rafique J, Braga AL. Angew. Chem. Int. Ed. 2021; 60: 18454
    • 3c Rammal F, Gao D, Boujnah S, Hussein AA, Lalevée J, Gaumont A.-C, Morlet-Savary F, Lakhdar S. ACS Catal. 2020; 10: 13710
    • 3d Tang X, Gan L, Zhang X, Huang Z. Sci. Adv. 2020; 6: eabc6688
    • 3e Liang Z, Guo H, Zhou G, Guo K, Wang B, Lei H, Zhang W, Zheng H, Apfel U.-P, Cao R. Angew. Chem. Int. Ed. 2021; 60: 8472
    • 4a Bica K, Gaertner P. Eur. J. Org. Chem. 2008; 3453
    • 4b Lecomte V, Bolm C. Adv. Synth. Catal. 2005; 347: 1666
  • 5 Kobayashi S, Kokubo M, Kawasumi K, Nagano T. Chem. Asian J. 2010; 5: 490
  • 6 Miyamura H, Sonoyama A, Hayrapetyan D, Kobayashi S. Angew. Chem. Int. Ed. 2015; 54: 10559
    • 7a Crisenza GE. M, Melchiorre P. Nat. Commun. 2020; 11: 803
    • 7b Cauwenbergh R, Das S. Synlett 2021; 33: 129
    • 7c McAtee RC, McClain EJ, Stephenson CR. J. Trends Chem. 2019; 1: 111
    • 7d Pitre SP, Overman LE. Chem. Rev. 2022; 122: 1717
  • 9 Yang J, Xie D, Zhou H, Chen S, Duan J, Huo C, Li Z. Adv. Synth. Catal. 2018; 360: 3471
    • 10a Atkins P, de Paula J. Atkins Physical Chemistry, 10th ed. Oxford University Press; Oxford: 2014
    • 10b Visan A, van Ommen JR, Kreutzer MT, Lammertink RG. H. Ind. Eng. Chem. Res. 2019; 58: 5349
    • 10c Noël T. In Photochemical Processes in Continuous-Flow Reactors: From Engineering Principles to Chemical Applications, Chap. 7. Noël T. World Scientific Publishing Europe; London: 2017: 245
    • 11a Bennett JA, Campbell ZS, Abolhasani M. Curr. Opin. Chem. Eng. 2019; 26: 9
    • 11b Bogdan AR, Dombrowski AW. J. Med. Chem. 2019; 62: 6422
    • 11c Rehm TH. Chem. Eur. J. 2020; 26: 16952
    • 12a Cambié D, Bottecchia C, Straathof NJ. W, Hessel V, Noël T. Chem. Rev. 2016; 116: 10276
    • 12b Noël T. J. Flow Chem. 2017; 7: 87
    • 13a Su Y, Straathof NJ. W, Hessel V, Noël T. Chem. Eur. J. 2014; 20: 10562
    • 13b Lévesque F, Seeberger PH. Org. Lett. 2011; 13: 5008
    • 14a Yun L, Zhao J, Tang X, Ma C, Yu Z, Meng Q.-W. Org. Proc. Res. Dev. 2021; 25: 1612
    • 14b Chen Y, Zhang Y, Zou H, Li M, Wang G, Peng M, Zhang J, Tang Z. Chem. Eng. J. (Amsterdam, Neth.) 2021; 423: 130226
    • 15a Wan L, Jiang M, Cheng D, Liu M, Chen F. React. Chem. Eng. 2022; 7: 490
    • 15b Bajada MA, Vijeta A, Savateev A, Zhang G, Howe D, Reisner E. ACS Appl. Mater. Interfaces 2020; 12: 8176
    • 16a Buglioni L, Raymenants F, Slattery A, Zondag SD. A, Noël T. Chem. Rev. 2022; 122: 2752
    • 16b Donnelly K, Baumann M. J. Flow Chem. 2021; 11: 223
    • 16c Kobayashi S. Chem. Asian J. 2016; 11: 425
    • 16d Xie J, Zhu C, Li Y, Xie J. Synlett 2020; 32: 387
  • 17 Zhao J, Yang F, Yu Z, Tang X, Wu Y, Ma C, Meng Q. Chem. Commun. 2019; 55: 13008
    • 18a Sun J.-G, Yang H, Li P, Zhang B. Org. Lett. 2016; 18: 5114
    • 18b Zhou L, Okugawa N, Togo H. Eur. J. Org. Chem. 2017; 6239
    • 18c Yang J, Liu C, Zhou H, Fan R, Ma B, Li Z. Org. Biomol. Chem. 2021; 19: 5572
    • 18d Das A, Thomas KR. J. Green Chem. 2022; 24: 4952
  • 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.