Catalytic Generation of Radicals from Nitroalkanes

This paper is dedicated to Professor Masahiro Murakami on the occasion of his retirement.

Abstract

A new protocol for the catalytic denitrative generation of radicals from nitroalkanes was disclosed. 9-Fluorenol acts as a single-electron transfer catalyst that reduces nitroalkanes to promote the C-NO₂ bond cleavage, followed by the formation of alkyl radicals. The obtained radicals participate in diverse transformations such as hydrogenation, Giese addition, spirocyclization, and Minisci reactions by using appropriate trapping reagents. The present system outperforms conventional methods using tin hydrides in terms of cost, toxicity, and experimental operations.

Key words

nitroalkane - 9-fluorenol - single-electron transfer - denitration - radical - organocatalysis

Publication History

Received: 12 August 2022

Accepted after revision: 13 September 2022

Accepted Manuscript online:
13 September 2022

Article published online:
19 October 2022

• References and Notes

• 1 New address: M. Kashihara, Research Institute for Interdisciplinary Science, Okayama University, Okayama, 700-8530, Japan.
• 2a Studer A, Curran DP. Angew. Chem. Int. Ed. 2016; 55: 58
• 2b Crespi S, Fagnoni M. Chem. Rev. 2020; 120: 9790
• 3 Twilton J, Le CC, Zhang P, Shaw MH, Evans RW, MacMillan DW. C. Nat. Rev. Chem. 2017; 1: 0052
• 4a Horn EJ, Rosen BR, Baran PS. ACS Cent. Sci. 2016; 2: 302
• 4b Zhu C, Ang NW. J, Meyer TH, Qiu Y, Ackermann L. ACS Cent. Sci. 2021; 7: 415
• 5a Luzzio FA. Tetrahedron 2001; 57: 915
• 5b Noble A, Anderson JC. Chem. Rev. 2013; 113: 2887
• 5c Ballini R, Palmieri A, Righi P. Tetrahedron 2007; 63: 12099
• 5d Zheng P.-F, An Y, Jiao Z.-Y, Shi Z.-B, Zhang F.-M. Curr. Org. Chem. 2019; 14: 1560
• 6a Ono N, Miyake H, Kaji A. J. Synth. Org. Chem. Jpn. 1985; 43: 121
• 6b Korth H.-G, Sustmann R, Dupuis J, Giese B. Chem. Ber. 1987; 120: 1197
• 6c Kamimura A, Ono N. Bull. Chem. Soc. Jpn. 1988; 61: 3629
• 6d Ono N, Kaji A. Synthesis 1986; 693
• 7 Zhang S, Li P, Li Z.-H. Comp. Biochem. Physiol., Part C: Toxicol. Pharmacol. 2021; 246: 109054
• 8a Tormo J, Hays DS, Fu GC. J. Org. Chem. 1998; 63: 5296
• 8b Fessard TC, Motoyoshi H, Carreira EM. Angew. Chem. Int. Ed. 2007; 46: 2078
• 9a Rezazadeh S, Devannah V, Watson DA. J. Am. Chem. Soc. 2017; 139: 8110
• 9b Zheng C, You S.-L. ACS Cent. Sci. 2021; 7: 432
• 9c Ballini R, Palmieri A. Adv. Synth. Catal. 2018; 360: 2240
• 10 Šepič E, Bricelj M, Leskovšek H. Chemosphere 2003; 52: 1125
• 11a Guthrie RD, Wesley DP, Pendygraft GW, Young AT. J. Am. Chem. Soc. 1976; 98: 5870
• 11b Guthrie RD, Hartmann C, Neill R, Nutter DE. J. Org. Chem. 1987; 52: 736
• 11c Kornblum N, Chen SI, Kelly WJ. J. Org. Chem. 1988; 53: 1830
• 12a Hoffmann AK, Hodgson WG, Maricle DL, Jura WH. J. Am. Chem. Soc. 1964; 86: 631
• 12b Ohmori H, Furusako S, Kashu M, Ueda C, Masui M. Chem. Pharm. Bull. 1984; 32: 3345
• 12c Weis CD, Newkome GR. Synthesis 1995; 1053
• 13a Boit TB, Mehta MM, Garg NK. Org. Lett. 2019; 21: 6447
• 13b Ishida N, Kamae Y, Ishizu K, Kamino Y, Naruse H, Murakami M. J. Am. Chem. Soc. 2021; 143: 2217
• 14 Compound 3a was formed after the reaction with 3d. Decomposition of 3d under the reaction conditions is another possible reason for higher activity.
• 15a McIntosh JM, Schram CK. Can. J. Chem. 1977; 55: 3755
• 15b Clive DL. J, Chittattu G, Wong CK. J. Chem. Soc., Chem. Commun. 1978; 41
• 16 Povie G, Ford L, Pozzi D, Soulard V, Villa G, Renaud P. Angew. Chem. Int. Ed. 2016; 55: 11221
• 17a Sharma S, Sultan S, Devari S, Shah BA. Org. Biomol. Chem. 2016; 14: 9645
• 17b Leifert D, Studer A. Angew. Chem. Int. Ed. 2020; 59: 74
• 18 Mendkovich AS, Syroeshkin MA, Nasybullina DV, Mikhailov MN, Gultyai VP, Elinson MN, Rusakov AI. Electrochim. Acta 2016; 191: 962
• 19 Bordwell FG, Harrelson JA. Jr. J. Am. Chem. Soc. 1989; 111: 1052
• 20 The redox potential of intermediate I is not available according to ref. 18. We also failed in determining it by CV.
• 21 Tanner DD, Harrison DJ, Chen J, Kharrat A, Wayner DD. M, Griller D, McPhee DJ. J. Org. Chem. 1990; 55: 3321
• 22a Mendkovich AS, Syroeshkin MA, Mikhailov MN, Ranchina DV, Rusakov AI. Russ. Chem. Bull. 2013; 62: 1668
• 22b Canby DS, Cheek GT. ECS Trans. 2007; 3: 609
• 23a Markle TF, Darcy JW, Mayer JM. Sci. Adv. 2018; 4: eaat5776
• 23b Sayfutyarova ER, Goldsmith ZK, Hammes-Schiffer S. J. Am. Chem. Soc. 2018; 140: 15641
• 24 Srikanth GS. C, Castle SL. Tetrahedron 2005; 61: 10377
• 25a Ono N, Miyake H, Kamimura A, Hamamoto I, Tamura R, Kaji A. Tetrahedron 1985; 41: 4013
• 25b Newkome GR, Arai S, Fronczek FR, Moorefield CN, Lin X, Weis CD. J. Org. Chem. 1993; 58: 898
• 25c Ono N, Miyake H, Kaji A. Chem. Lett. 1985; 14: 635
• 26 Wille U. Chem. Rev. 2013; 113: 813
• 27 Yang W.-C, Zhang M.-M, Feng J.-G. Adv. Synth. Catal. 2020; 362: 4446
• 28a Duncton MA. J. MedChemComm 2011; 2: 1135
• 28b Proctor RS. J, Phipps RJ. Angew. Chem. Int. Ed. 2019; 58: 13666
• 29 Typical Procedure for the Denitrative Radical Transformation of Nitroalkanes A 15-mL vial equipped with a magnetic stirrer bar was charged with nitroalkane 1 (0.60 mmol), radical acceptor 2, 6, 8, or 10 (0.60–1.8 mmol), K₃PO₄ (0.90–1.8 mmol), and 2-propanol (3.0–6.0 mL) under a nitrogen atmosphere. The resulting mixture was stirred at 110 °C. After completion of the reaction, the mixture was filtered through a short pad of Celite^® and eluted with EtOAc. All volatiles were removed in vacuo, and the residue was purified by a silica gel column chromatography. Analytical Data for 4l ¹H NMR (400 MHz, acetone-d ₆): δ = 7.36–7.19 (m, 5 H), 2.99 (dd, J = 14.2, 5.0 Hz, 1 H), 2.70 (dd, J = 14.0, 8.9 Hz, 1 H), 2.59–2.42 (m, 1 H), 1.65–1.45 (m, 2 H), 0.93 (td, J = 7.6, 0.9 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 138.6, 129.0, 128.5, 128.4 (q, J = 280.8 Hz), 126.5, 45.9 (q, J = 24.0 Hz), 33.7, 20.3, 11.2. ¹⁹F NMR (376 MHz, CDCl₃): δ = –70.1. HRMS (EI) (+): m/z [M]⁺ calcd for C₁₁H₁₃F₃: 202.0969; found: 202.0963. Analytical Data for 9e ¹H NMR (400 MHz, acetone-d ₆): δ = 7.39–7.33 (m, 2 H), 7.27–7.20 (m, 3 H), 7.11 (d, J = 10.2 Hz, 2 H), 6.46 (s, 1 H), 6.19 (d, J = 10.1 Hz, 2 H), 2.16 (s, 2 H), 1.74–1.58 (m, 6 H), 1.57–1.36 (m, 4 H). ¹³C NMR (101 MHz, CDCl₃): δ = 185.9, 156.4, 140.7, 140.6, 135.3, 128.3, 127.9, 127.8, 125.9, 56.0, 48.7, 48.6, 38.8, 25.6, 23.3. ESI-HRMS (+): m/z [M + Na]⁺ calcd for C₂₁H₂₂ONa: 313.1563; found: 313.1561. Experimental details and analytical data for other compounds are provided in the Supporting Information.