A Reductive Deuteration Approach to the Efficient Synthesis of Deuterated Polymers

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

Publication History

Received: 25 January 2022

Accepted: 13 March 2022

Accepted Manuscript online:
13 March 2022

Article published online:
19 April 2022

• 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 DOI: 10.1126/sciadv.abb4246.
• 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