Photoinduced Alkylation of Diazines with N-(Acyloxy)phthalimides in the Presence of Triethylamine

Itziar Guerrero; Eugene Yew Kun Tan; Yuliang Liu; Lee J. Edwards; Shunsuke Chiba

doi:10.1055/a-2182-7416

Synthesis, Table of Contents

Synthesis 2024; 56(21): 3261-3276
DOI: 10.1055/a-2182-7416

paper

Special Issue PSRC-10 (10th Pacific Symposium on Radical Chemistry)

Photoinduced Alkylation of Diazines with N-(Acyloxy)phthalimides in the Presence of Triethylamine

Itziar Guerrero

^aSchool of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637371, Singapore

,

Eugene Yew Kun Tan

^aSchool of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637371, Singapore

,

Yuliang Liu

^aSchool of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637371, Singapore

,

Lee J. Edwards

^bDrug Substance Development, GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG1 2NY, UK

,

Shunsuke Chiba ∗

^aSchool of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637371, Singapore

› Author Affiliations

Abstract

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Dedicated to Professor Shigeru Yamago on the occasion of his 60^th birthday

Abstract

A photochemical protocol for the alkylation of diazines (pyrimidines, pyrazines, and pyridazines) with N-(acyloxy)phthalimides has been developed. The process is facilitated by the presence of triethylamine under irradiation with 427–390 nm light; this enables rapid cross-coupling reactions to construct a wide range of alkylated diazines.

Key words

N-(acyloxy)phthalimides - diazines - radicals - electron donor–acceptor (EDA) complexes - Minisci-type alkylation

Full Text

References

References
1 https://njardarson.lab.arizona.edu/content/top-pharmaceuticals-poster
2 https://www.acs.org/content/dam/acsorg/events/drug-discovery/slides/2019-09-19-recent-crop-protection-poster.pdf
3 Minisci F, Bernardi R, Bertini F, Galli R, Perchinummo M. Tetrahedron 1971; 27: 3575
4 Minisci F, Fontana F, Vismara E. J. Heterocycl. Chem. 1990; 27: 79-96
5 Duncton MA. J. Med. Chem. Commun. 2011; 2: 1135
6 Proctor RS. J, Phipps RJ. Angew. Chem. Int. Ed. 2019; 58: 13666
7 Sun AC, McAtee RC, McClain EJ, Stephenson CR. J. Synthesis 2019; 51: 1063
8 McClain EJ, Wortman AK, Stephenson CR. J. Chem. Sci. 2022; 13: 12158
9 Sun AC, McClain EJ, Beatty JW, Stephenson CR. J. Org. Lett. 2018; 20: 3487
10 Beatty JW, Douglas JJ, Miller R, McAtee RC, Cole KP, Stephenson CR. J. Chem 2016; 1: 456
11 Beatty JW, Douglas JJ, Cole KP, Stephenson CR. J. Nat. Commun. 2015; 6: 7919
12 Okada K, Okamoto K, Morita N, Okubo K, Oda M. J. Am. Chem. Soc. 1991; 113: 9401
13 Okada K, Okamoto K, Oda M. J. Am. Chem. Soc. 1988; 110: 8736
14 Karmakar S, Silamkoti A, Meanwell NA, Mathur A, Gupta AK. Adv. Synth. Catal. 2021; 363: 3693
15 Murarka S. Adv. Synth. Catal. 2018; 360: 1735
16 Proctor RS. J, Davis HJ, Phipps RJ. Science 2018; 360: 419
17 Sherwood TC, Li N, Yazdani AN, Dhar TG. M. J. Org. Chem. 2018; 83: 3000
18 Cheng W.-M, Shang R, Fu M.-C, Fu Y. Chem. Eur. J. 2017; 23: 2537
19 Cheng W.-M, Shang R, Fu Y. ACS Catal. 2017; 7: 907
20 Fu M.-C, Shang R, Zhao B, Wang B, Fu Y. Science 2019; 363: 1429
21 Bosque I, Bach T. ACS Catal. 2019; 9: 9103
22 de Pedro Beato E, Spinnato D, Zhou W, Melchiorre P. J. Am. Chem. Soc. 2021; 143: 12304
23 Sharique M, Majhi J, Dhungana RK, Kammer LM, Krumb M, Lipp A, Romero E, Molander GA. Chem. Sci. 2022; 13: 5701
24 Tasnim T, Ayodele MJ, Pitre SP. J. Org. Chem. 2022; 87: 10555
25 Yang Z, Liu Y, Cao K, Zhang X, Jiang H, Li J. Beilstein J. Org. Chem. 2021; 17: 771
26 Crisenza GE. M, Mazzarella D, Melchiorre P. J. Am. Chem. Soc. 2020; 142: 5461
27 Yuan Y.-q, Majumder S, Yang M.-h, Guo S.-r. Tetrahedron Lett. 2020; 62: 151506
28 Lima CG. S, Lima TM, Duarte M, Jurberg ID, Paixão MW. ACS Catal. 2016; 6: 1389
29 Liang D, Chen J.-R, Tan L.-P, He Z.-W, Xiao W.-J. J. Am. Chem. Soc. 2022; 144: 6040
30 Reid JP, Procter RS. J, Sigman MS, Phipps RJ. J. Am. Chem. Soc. 2019; 141: 19178
31 Graham MA, Noonan G, Cherryman JH, Douglas JJ, Gonzalez M, Jackson LV, Leslie K, Liu Z.-q, McKinney D, Munday RH, Parsons CD, Whittaker DT. E, Zhang E.-x, Zhang J.-w. Org. Process Res. Dev. 2021; 25: 57
32 2-Chloropyrimidine (2) ($3.9/g:https://www.sigmaaldrich.com/US/en/product/aldrich/193291) is much cheaper than N-(acyloxy)phthalimide 1 ($65/g: https://www.combi-blocks.com/cgi-bin/find.cgi?JP-4977)
33 Yoon UC, Mariano PS. Acc. Chem. Res. 2001; 34: 523
34 Anderson JM, Measom ND, Murphy JA, Poole DL. Angew. Chem. Int. Ed. 2021; 60: 24754
35 Wu C, Ying T, Yang X, Su W, Dushkin AV, Yu J. Org. Lett. 2021; 23: 6423
36 Shore DG. M, Wasik KA, Lyssikatos JP, Estrada AA. Tetrahedron Lett. 2015; 56: 4063
37 O’Hara F, Blackmond DG, Baran PS. J. Am. Chem. Soc. 2013; 135: 12122
38 Xie X, Zhang Y, Hao J, Wan W. Org. Biomol. Chem. 2020; 18: 400
39 Huang Q, Qin L, Zard SZ. Tetrahedron 2018; 74: 5804
40 Bohman B, Berntsson B, Dixon RC. M, Stewart CD, Barrow RA. Org. Lett. 2014; 16: 2787
41 Buzzetti L, Crisenza GE. M, Melchiorre P. Angew. Chem. Int. Ed. 2019; 58: 3730
42 Wortman AK, Stephenson CR. J. Chem 2023; 9: 2390
43 The process from radical intermediate IV to product 3 could be mediated by the radical anion of 3 (formed by deprotonation before SET). We observed an irreversible reduction wave of 3 in the CV measurement (see the SI) and determined the reduction potential of 3 as E _1/2 = –2.06 V vs. SCE. As the reduction potentials of N-(acyloxy)phthalimide 1 is –1.29 V vs. SCE (see the SI), the radical anion of 3 could potentially function as an electron carrier to N-(acyloxy)phthalimide 1 to facilitate the proposed chain propagation. On the other hand, hydrodechlorination of 2-chloropyrimidine (2) (E _1/2 = –1.75 V vs. SCE) and 3 was not observed at all.
44 Studer A, Curran DP. Angew. Chem. Int. Ed. 2011; 50: 5018
45 The alkylation of other diazines especially with the reaction time longer than 5 h (Scheme 3) could also be facilitated by the non-chain redox mechanism.
46 Huang C.-Y, Li J, Li C.-J. Nat. Commun. 2021; 12: 4010

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