Efficient Flow Electrochemical Alkoxylation of Pyrrolidine-1-carbaldehyde

Nasser Amri; Ryan A. Skilton; Duncan Guthrie; Thomas Wirth

doi:10.1055/s-0037-1611774

Synlett, Table of Contents

Synlett 2019; 30(10): 1183-1186
DOI: 10.1055/s-0037-1611774

cluster

Efficient Flow Electrochemical Alkoxylation of Pyrrolidine-1-carbaldehyde

Nasser Amri

^aSchool of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT, UK Email: wirth@cf.ac.uk

,

Ryan A. Skilton

^bVapourtec Ltd., 21 Park Farm Business Centre, Bury St Edmunds, IP28 6TS, UK

,

Duncan Guthrie

^bVapourtec Ltd., 21 Park Farm Business Centre, Bury St Edmunds, IP28 6TS, UK

,

Thomas Wirth *

^aSchool of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT, UK Email: wirth@cf.ac.uk

› Author Affiliations

Abstract

All articles of this category

Published as part of the Cluster Electrochemical Synthesis and Catalysis

Abstract

We report on the optimization of the alkoxylation of pyrrolidine-1-carbaldehyde by using a new electrochemical microreactor. Precise control of the reaction conditions permits the synthesis of either mono- or dialkoxylated reaction products in high yields.

Key words

C–H activation - electrochemistry - flow chemistry - heterocycles - alkoxylation - pyrrolidinecarbaldehyde

Full Text

References

References and Notes

1a Little RD, Moeller KD. Chem. Rev. 2018; 118: 4483
1b Francke R, Schille B, Roemelt M. Chem. Rev. 2018; 118: 4631
1c Yoshida JI, Shimizu A, Hayashi R. Chem. Rev. 2018; 118: 4702
1d Moeller KD. Chem. Rev. 2018; 118: 4817
1e Nutting JE, Rafiee M, Stahl SS. Chem. Rev. 2018; 118: 4834

2a Frontana-Uribe BA, Little RD, Ibanez JG, Palma A, Vasquez-Medrano R. Green Chem. 2010; 12: 2099
2b Organic Electrochemistry, 5th ed. . Hammerich O, Speiser B. CRC Press; Boca Raton: 2015
2c Horn EJ, Rosen BR, Baran PS. ACS Cent. Sci. 2016; 2: 302

3a Yoshida J. Electrochem. Soc. Interface 2009; (Summer) 40
3b Folgueiras-Amador AA, Wirth T. J. Flow Chem. 2017; 7: 94
3c Atobe M, Tateno H, Matsumura Y. Chem. Rev. 2018; 118: 4541
3d Pletcher D, Green RA, Brown RC. D. Chem. Rev. 2018; 118: 4573
3e Folgueiras-Amador AA, Wirth T. In Flow Chemistry in Organic Synthesis . Jamison TF, Koch G. Thieme; Stuttgart: 2018. Chap. 5, 147

4 Yoo SJ, Li L.-J, Zeng C.-C, Little RD. Angew. Chem. Int. Ed. 2015; 54: 3744

5a Horii D, Atobe M, Fuchigami T, Marken F. Electrochem. Commun. 2005; 7: 35
5b Horcajada R, Okajima M, Suga S, Yoshida J.-i. Chem. Commun. 2005; 1303
5c He P, Watts P, Marken F, Haswell SJ. Angew. Chem. Int. Ed. 2006; 45: 4146
5d Kuleshova J, Hill-Cousins JT, Birkin PR, Brown RC. D, Pletcher D, Underwood TJ. Electrochim. Acta 2011; 56: 4322
5e Attour A, Dirrenberger P, Rode S, Ziogas A, Matlosz M, Lapicque F. Chem. Eng. Sci. 2011; 66: 480
5f Kashiwagi T, Elsler B, Waldvogel SR, Fuchigami T, Atobe M. J. Electrochem. Soc. 2013; 160: G3058

6a Watts K, Gattrell W, Wirth T. Beilstein J. Org. Chem. 2011; 7: 1108
6b Arai K, Watts K, Wirth T. ChemistryOpen 2014; 3: 23
6c Arai K, Wirth T. Org. Process Res. Dev. 2014; 18: 1377
6d Folgueiras-Amador AA, Philipps K, Guilbaud S, Poelakker J, Wirth T. Angew. Chem. Int. Ed. 2017; 56: 15446
6e Folgueiras-Amador AA, Qian X.-Y, Xu H.-C, Wirth T. Chem. Eur. J. 2018; 24: 487
6f Gao W.-C, Xiong Z.-Y, Pirhaghani S, Wirth T. Synthesis 2019; 51: 276
6g Islam M, Kariuki BM, Shafiq Z, Wirth T, Ahmed N. Eur. J. Org. Chem. 2019; 1371

7 For details of the Ion electrochemical reactor, see: https://www.vapourtec.com/products/flow-reactors/ion-electrochemical-reactor-features/ (accessed Mar 15, 2019).

8a Kuleshova J, Hill-Cousins JT, Birkin PR, Brown RC. D, Pletcher D, Underwood TJ. Electrochim. Acta 2012; 69: 197
8b Green RA, Brown RC. D, Pletcher D, Harji B. Org. Process Res. Dev. 2015; 19: 1424
8c Green RA, Brown RC. D, Pletcher D, Harji B. Electrochem. Commun. 2016; 73: 63
8d Folgueiras-Amador AA, Jolley KE, Birkin PR, Brown RC. D, Pletcher D, Pickering S, Sharabi M, de Frutos O, Mateos C, Rincón JA. Electrochem. Commun. 2019; 100: 6

9 18% Cr, 8% Ni.
10 Amemiya F, Kashiwagi T, Fuchigami T, Atobe M. Chem. Lett. 2011; 40: 606
11 Cedheim L, Eberson L, Helgee B, Nyberg K, Servin R, Sternerup H. Acta Chem. Scand., Ser. B 1975; 29: 617
12 Chapman MR, Shafi YM, Kapur N, Nguyen BN, Willans CE. Chem. Commun. 2015; 51: 1282

13a Liebner R, Schmid P, Adelwöhrer C, Rosenau T. Tetrahedron 2007; 63: 11817
13b Stewart WE, Siddall TH. Chem. Rev. 1970; 70: 517

14 Mitzlaff M, Warning K, Jensen H. Liebigs Ann. Chem. 1978; 1713
15 2-Methoxypyrrolidine-1-carbaldehyde (2); Typical ProcedureA 0.1 M solution of aldehyde 1 in MeOH (60 mL) containing Et₄NBF₄ (0.05 M) was sonicated to ensure complete dissolution of the reactant, then pumped through one microreactor at 0.5 mL/min by using a syringe pump or the Vapourtec E series, while a constant current of 640 mA was applied. The first 5 mL were discarded, and the remaining reaction mixture was collected for 110 min (55 mL). MeOH was removed under reduced pressure, and the crude product was washed with H₂O (50 mL), to remove the supporting electrolyte, then extracted with CH₂Cl₂ (3 × 30 mL). The organic layers were combined, dried (MgSO₄), filtered, evaporated, and dried under high vacuum. The residue was purified by chromatography [silica gel, hexane–EtOAc (1:1)] to give a colorless oil; yield: 629 mg (89%). The NMR spectra showed the presence of a ~5:1 mixture of rotamers.¹H NMR (400 MHz, CDCl₃): δ (major) = 8.40 (s, 1 H), 4.92 (d, J = 4.8 Hz, 1 H), 3.58−3.40 (m, 2 H), 3.26 (s, 3 H), 2.13−1.79 (m, 4 H); δ (minor) = 8.29 (s, 1 H), 5.37 (d, J = 4.8 Hz, 1 H), 3.58−3.40 (m, 2 H), 3.38 (s, 3 H), 2.13−1.79 (m, 4 H). ¹³C NMR (101 MHz, CDCl₃): δ (major) = 161.4, 89.7, 54.4, 42.7, 31.8, 21.4; δ (minor) = 162.6, 85.5, 56.6, 45.2, 31.9, 22.1.

Supplementary Material

Supporting Information