A Reductive Deuteration Approach to the Efficient Synthesis of Deuterated Polymers

Lei Ning; Lijun Wang; Mengqi Peng; Zixuan Qin; Hengzhao Li; Shangzhong Liu; Yanhong Dong; Jie An

doi:10.1055/a-1796-7064

Synlett, Table of Contents

Synlett 2022; 33(08): 771-776
DOI: 10.1055/a-1796-7064

letter

A Reductive Deuteration Approach to the Efficient Synthesis of Deuterated Polymers

Lei Ning

^aDepartment of Nutrition and Health, China Agricultural University, Beijing 100193, P. R. of China

^bInnovation Center of Pesticide Research, China Agricultural University, Beijing 100193, P. R. of China

,

Lijun Wang

^aDepartment of Nutrition and Health, China Agricultural University, Beijing 100193, P. R. of China

^bInnovation Center of Pesticide Research, China Agricultural University, Beijing 100193, P. R. of China

,

Mengqi Peng

^aDepartment of Nutrition and Health, China Agricultural University, Beijing 100193, P. R. of China

^bInnovation Center of Pesticide Research, China Agricultural University, Beijing 100193, P. R. of China

,

Zixuan Qin

^aDepartment of Nutrition and Health, China Agricultural University, Beijing 100193, P. R. of China

,

Hengzhao Li

^aDepartment of Nutrition and Health, China Agricultural University, Beijing 100193, P. R. of China

^bInnovation Center of Pesticide Research, China Agricultural University, Beijing 100193, P. R. of China

,

Shangzhong Liu

^bInnovation Center of Pesticide Research, China Agricultural University, Beijing 100193, P. R. of China

,

Yanhong Dong∗

^bInnovation Center of Pesticide Research, China Agricultural University, Beijing 100193, P. R. of China

,

Jie An ∗

^aDepartment of Nutrition and Health, China Agricultural University, Beijing 100193, P. R. of China

› Author Affiliations

Abstract

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Abstract

Deuterated polymers have wide applications but limited synthetic methods. In this study, we report an efficient two-step approach for the synthesis of deuterated polyesters and polyurethanes. Firstly, two practical single-electron transfer (SET) reductive-deuteration methods have been developed for site-selective introduction of C(sp³)–D into diol monomers. Nine deuterated diol monomers with high deuterium incorporations were synthesized under SmI₂–D₂O and/or Na-EtOD-d ₁ SET reductive-deuteration conditions. Then, six typical deuterated polyesters and polyurethanes were synthesized using those deuterated monomers under typical polymerization conditions. In all the synthesized polymers, high deuterium incorporation was fully maintained, which showcased the potential application of this approach for the synthesis of polymers with site-specific deuterium labelling.

Key words

reductive deuteration - single electron transfer - deuterated diol - deuterated polymer - selective deuteration

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References

References and Notes

1a Mutlib AE. Chem. Res. Toxicol. 2008; 21: 1672
1b Atzrodt J, Derdau V, Kerr WJ, Reid M. Angew. Chem. Int. Ed. 2018; 57: 1758
1c Pirali T, Serafini M, Cargnin S, Genazzani AA. J. Med. Chem. 2019; 62: 5276
1d Li L, Jakowski J, Do C, Hong K. Macromolecules 2021; 54: 3555
1e Thiyagarajan S, Gunanathan C. Org. Lett. 2020; 22: 6617
1f Vang ZP, Reyes A, Sonstrom RE, Holdren MS, Sloane SE, Alansari IY, Neill JL, Pate BH, Clark JR. J. Am. Chem. Soc. 2021; 143: 7707
1g Thiyagarajan S, Gunanathan C. Synlett 2019; 30: 2027
1h Sloane SE, Reyes A, Vang ZP, Li L, Behlow KT, Clark JR. Org. Lett. 2020; 22: 9139
1i Milster S, Grünbaum T, Bange S, Kurrmann S, Kraus H, Stoltzfus DM, Leung AE, Darwish TA, Burn PL, Boehme C, Lupton JM. Angew. Chem. 2020; 132: 9474

2 Schmidt C. Nat. Biotechnol. 2017; 35: 493
3 Tong CC, Hwang KC. J. Phys. Chem. C 2007; 111: 3490
4 Anselmi E, Raby J, Balland-Longeau A. Fusion Sci. Technol. 2004; 45: 157
5 Chang D, Li T, Li L, Jakowski J, Huang J, Keum JK, Lee B, Bonnesen PV, Zhou M, Garashchuk S, Sumpter BG, Hong K. Macromolecules 2018; 51: 9393
6 Bates FS, Keith HD, McWhan DB. Macromolecules 1987; 20: 3065
7 Yoneyama S, Kodama T, Kikuchi K, Fujisawa T, Yamaguchi A, Sumiyama A, Shuku Y, Aoyagi S, Fujita W. Dalton Trans. 2016; 45: 16774

8a Hu R, Kan W, Xiong X, Wei H. J. Nucl. Mater. 2017; 492: 171
8b Zoller DL, Johnston MV, Qian K, Lohse DJ. Macromolecules 2000; 33: 5388

9a Kang S, Zeng Y, Lodge TP, Bates FS, Brant P, López-Barrón CR. Polymer 2016; 102: 99
9b Habersberger BM, Baugh DW. Macromolecules 2018; 51: 1290
9c Ertem SP, Onuoha CE, Wang H, Hillmyer MA, Reineke TM, Lodge TP, Bates FS. Macromolecules 2020; 53: 6043

10a Farrell WS, Orski SV, Kotula AP, Baugh DW. III, Snyder CR, Beers KL. Macromolecules 2019; 52: 5741
10b Li L, Chang D, Arras MM. L, Li W, Li T, Keum JK, Bonnesen PV, Peng X, Hong K. J. Polym. Sci., Part B: Polym. Phys. 2019; 57: 771

11 Xiong J, Thangavel G, Wang J, Zhou X, Lee PS. Sci. Adv. 2020; 6: eabb4246

12a Tsonev T, Herzog M, Nenkova S. Open Chem. 2013; 11: 2058
12b Peterson GI, Childers EP, Li H, Dobrynin AV, Becker ML. Macromolecules 2017; 50: 4300

13a Maegawa T, Fujiwara Y, Inagaki Y, Monguchi Y, Sajiki H. Adv. Synth. Catal. 2008; 350: 2215
13b Kar S, Goeppert A, Sen R, Kothandaraman J, Surya Prakash GK. Green Chem. 2018; 20: 2706
13c Chatterjee B, Gunanathan C. Org. Lett. 2015; 17: 4794

14a Marchand AP, Satyanarayana N, McKenney RL, Struck SR. J. Labelled Compd. Radiopharm. 1988; 25: 971
14b Zimmermann H. Liq. Cryst. 1989; 4: 591
14c Oliveira C, Morais GR, Imai M, Inohae E, Yamamoto C, Mataka S, Thiemann T. J. Chem. Res. 2010; 34: 158
14d Smith LB, Armstrong RJ, Matheau-Raven D, Donohoe TJ. J. Am. Chem. Soc. 2020; 142: 2514
14e Fukuzawa S, Tsuchimoto T, Hiyama T. J. Org. Chem. 1997; 62: 151

15a Li H, Peng M, Lai Z, Ning L, Chen X, Zhang X, Wang P, Szostak R, Szostak M, An J. Chem. Commun. 2021; 57: 5195
15b Li H, Hou Y, Lai Z, Ning L, Li A, Li Y, An J. Synlett 2021; 32: 1241
15c Luo S, Weng C, Ding Y, Ling C, Szostak M, Ma X, An J. Synlett 2021; 32: 51
15d Ning L, Li H, Lai Z, Szostak M, Chen X, Dong Y, Jin S, An J. J. Org. Chem. 2021; 86: 2907
15e Li H, Hou Y, Liu C, Lai Z, Ning L, Szostak R, Szostak M, An J. Org. Lett. 2020; 22: 1249

16a Zhang B, Li H, Ding Y, Yan Y, An J. J. Org. Chem. 2018; 83: 6006
16b Han M, Ding Y, Yan Y, Li H, Luo S, Adijiang A, Ling Y, An J. Org. Lett. 2018; 20: 3010
16c Li H, Zhang B, Dong Y, Liu T, Zhang Y, Nie H, Yang R, Ma X, Ling Y, An J. Tetrahedron Lett. 2017; 58: 2757
16d Han M, Ma X, Yao S, Ding Y, Yan Z, Adijiang A, Wu Y, Li H, Zhang Y, Lei P, Ling Y, An J. J. Org. Chem. 2017; 82: 1285

17a Typical Procedure for the Preparation of Model Compound 2a Using Na-EtOD-d ₁ To a solution of 1a (69.1 mg, 0.300 mmol, 1.00 equiv) in anhydrous hexane (2.50 mL) was added EtOD-d ₁ (3.60 mmol, 12.0 equiv) followed by Na dispersions in oil (34.5 wt%, 3.60 mmol, 12.0 equiv) under Ar at 0 ℃, and the resulting solution was stirred vigorously. After 20 min, the reaction was quenched by an aqueous solution of NaHCO₃ (5.0 mL, saturated), and the reaction mixture was diluted with EtOAc (10 mL) and brine (10 mL). The aqueous layer was extracted with EtOAc (3 × 15 mL), the organic layers were combined, dried over Na₂SO₄, filtered, and concentrated. The crude product was purified by flash chromatography (silica, 20–75% EtOAc/hexanes) to afford 2a (33.9 mg, 95%) as a white solid. Percentage of exchanged protons are determined by ¹H NMR spectroscopy indicated in square brackets. ¹H NMR (300 MHz, CDCl₃): δ = 1.61–1.42 (m, 6 H), 1.41–1.23 (m, 12 H). ¹³C{¹H}NMR (75 MHz, CDCl₃): δ = 62.4 (m), 32.7, 29.6, 29.5, 25.8.

18 Typical Procedure for the Preparation of Model Compound 2a Using SmI₂–Et₃N–D₂O To a solution of samarium(II) iodide (0.100 M in THF; 30.0 mL, 3.00 mmol, 15.0 equiv) were added Et₃N (0.911 g, 9.00 mmol, 45.0 equiv) and D₂O (180 mg, 9.00 mmol, 45.0 equiv) followed by a solution of 1a (29.2 mg, 0.200 mmol, 1.00 equiv) in anhydrous THF (1.00 mL) under Ar at room temperature, and the resulting solution was stirred vigorously. After 2 h, the excess of SmI₂ was oxidized by bubbling air through the reaction mixture. The reaction mixture was diluted with NaOH (1 M, 10 mL) and EtOAc (20 mL). The aqueous layer was extracted with EtOAc (3 × 15 mL), the organic layers were combined, washed with saturated Na₂S₂O₃ (5 mL) and brine (5 mL), dried over Na₂SO₄, filtered, and concentrated. The crude product was purified by flash chromatography (silica, 20–75% EtOAc/hexanes) to afford 2a (33.9 mg, 95%) as a white solid. Percentage of exchanged protons are determined by ¹H NMR spectroscopy indicated in square brackets in Scheme 2. ¹H NMR (300 MHz, CDCl₃): δ = 1.61–1.42 (m, 6 H), 1.41–1.23 (m, 12 H). ¹³C{¹H}NMR (75 MHz, CDCl₃): δ = 62.4 (m), 32.7, 29.6, 29.5, 25.8.
19 Tanaka H, Kurihashi T. Polym. J. 2003; 35: 359
20 Sagara Y, Karman M, Verde-Sesto E, Matsuo K, Kim Y, Tamaoki N, Weder C. J. Am. Chem. Soc. 2018; 140: 1584
21 Jones RN. Can. J. Chem. 1962; 40: 301

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