Divergent Functionalization of Alkynes Enabled by Organic Photoredox Catalysis

Abstract

Direct functionalization of alkynes under oxidative conditions is challenging, as alkynes are usually recalcitrant towards typical oxidants. Herein, we communicate a strategy for the divergent functionalization of alkynes with photoexcited acridinium organic dyes, presumably via the formation of vinyl cation radicals as key intermediates. Based on the nature of the nucleophiles, different types of difunctionalized products were obtained in moderate to good yields. Addition of lithium Lewis acids resulted in a surprising reversal of diastereocontrol.

Key words

alkynes - pyrazoles - photoredox catalysis - diastereoselective - acridinium - mineral acids

Publication History

Received: 07 December 2022

Accepted after revision: 09 January 2023

Accepted Manuscript online:
09 January 2023

Article published online:
31 January 2023

• References and Notes

• 1 Fagnoni M, Dondi D, Ravelli D, Albini A. Chem. Rev. 2007; 107: 2725
• 2 Hoffmann N. J. Photochem. Photobiol., C 2008; 9: 43
• 3 Marin ML, Santos-Juanes L, Arques A, Amat AM, Miranda MA. Chem. Rev. 2012; 112: 1710
• 4 Ravelli D, Fagnoni M, Albini A. Chem. Soc. Rev. 2013; 42: 97
• 5 Fukuzumi S, Ohkubo K. Org. Biomol. Chem. 2014; 12: 6059
• 6 Romero NA, Nicewicz DA. Chem. Rev. 2016; 116: 10075
• 7 Holmberg-Douglas N, Nicewicz DA. Chem. Rev. 2022; 122: 1925
• 8 Hamilton DS, Nicewicz DA. J. Am. Chem. Soc. 2012; 134: 18577
• 9 Perkowski AJ, Nicewicz DA. J. Am. Chem. Soc. 2013; 135: 10334
• 10 Nguyen TM, Manohar N, Nicewicz DA. Angew. Chem. Int. Ed. 2014; 53: 6198
• 11 Romero NA, Nicewicz DA. J. Am. Chem. Soc. 2014; 136: 17024
• 12 Wilger DJ, Grandjean J.-MM, Lammert TR, Nicewicz DA. Nat. Chem. 2014; 6: 720
• 13 Morse PD, Nicewicz DA. Chem. Sci. 2015; 6: 270
• 14 Margrey KA, Nicewicz DA. Acc. Chem. Res. 2016; 49: 1997
• 15 Onuska NP. R, Schutzbach-Horton ME, Rosario Collazo JL, Nicewicz DA. Synlett 2020; 31: 55
• 16 Beller M, Seayad J, Tillack A, Jiao H. Angew. Chem. Int. Ed. 2004; 43: 3368
• 17 Trost BM, Ball ZT. Synthesis 2005; 853
• 18 Bhunia S, Ghosh P, Patra SR. Adv. Synth. Catal. 2020; 362: 3664
• 19 Chalotra N, Kumar J, Naqvi T, Shah BA. Chem. Commun. 2021; 57: 11285
• 20 Buriak JM, Allen MJ. J. Am. Chem. Soc. 1998; 120: 1339
• 21 Schroeder S, Strauch C, Gaelings N, Niggemann M. Angew. Chem. Int. Ed. 2019; 58: 5119
• 22 Pons A, Michalland J, Zawodny W, Chen Y, Tona V, Maulide N. Angew. Chem. Int. Ed. 2019; 58: 17303
• 23 Guo R, Qi X, Xiang H, Geaneotes P, Wang R, Liu P, Wang Y. Angew. Chem. Int. Ed. 2020; 59: 16651
• 24 Xuan J, Studer A. Chem. Soc. Rev. 2017; 46: 4329
• 25 Oh H, Ryou B, Park J, Kim M, Choi J.-H, Park C.-M. ACS Catal. 2021; 11: 13670
• 26 Wang B, Mccabe GE, Parrish MJ, Singh J, Zeller M, Deng Y. Adv. Synth. Catal. 2022; 364: 1179
• 27 Romero NA, Margrey KA, Tay NE, Nicewicz DA. Science 2015; 349: 1326
• 28 Ohkubo K, Mizushima K, Iwata R, Fukuzumi S. Chem. Sci. 2011; 2: 715
• 29 Katritzky AR, Yang B. J. Heterocycl. Chem. 1996; 33: 607
• 30 Bellucci G, Bianchini R, Vecchiani S. J. Org. Chem. 1987; 52: 3355
• 31 Härle H, Jochims JC. Chem. Ber. 1986; 119: 1400
• 32 Huang L, Rudolph M, Rominger F, Hashmi AS. K. Angew. Chem. Int. Ed. 2016; 55: 4808
• 33 Monos TM, McAtee RC, Stephenson CR. J. Science 2018; 361: 1369
• 34 MacKenzie IA, Wang L, Onuska NP. R, Williams OF, Begam K, Moran AM, Dunietz BD, Nicewicz DA. Nature 2020; 580: 76
• 35 Mallojjala SC, Nyagilo VO, Corio SA, Adili A, Dagar A, Loyer KA, Seidel D, Hirschi JS. J. Am. Chem. Soc. 2022; 144: 17692
• 36 Kaur S, Zhao G, Busch E, Wang T. Org. Biomol. Chem. 2019; 17: 1955
• 37 Alkyne Reaction with Amine Nucleophiles; Typical Procedure: To a 2-dram vial charged with a Teflon-coated stir was added alkyne (0.2 mmol, 1 equiv), amine (1.0 mmol, 5 equiv), diphenyl disulfide (4.37 mg, 0.1 mmol, 10 mol%), 3,6-di-tert-butyl-9-mesityl-10-phenylacridinium tetrafluoroborate (5.74 mg, 0.01 mmol) and anhydrous 1,2-dichloroethane (2 mL). The vial was then sealed with a Teflon-coated septum cap and the mixture was sparged with argon for 10 minutes. The mixture was then stirred under irradiation with 456 nm SynLED or 450 nm LED light for the indicated time. After completion, the reaction mixture was concentrated in vacuo and purified using silica gel chromatography with hexane to 10% EtOAc in hexanes as the eluent unless otherwise noted. (1-(4-Chlorophenyl)-2-phenylethane-1,2-diyl)bis(1H-pyrazole) (3e): Prepared by following the Typical Procedure. The title compound was isolated as a white solid. Without additional of LiNTf₂: after 30 h, 51% yield (35.7 mg) with 1:2.4 dr; With additional of LiNTf₂ (57.4 mg, 1 equiv): after 30 h, 67% yield (46.8 mg) with 8:1 dr. NMR data for the syn isomer: ¹H NMR (600 MHz, CDCl₃): δ = 7.49–7.42 (m, 6 H), 7.24 (dd, J = 2.3, 0.7 Hz, 1 H), 7.22–7.15 (m, 6 H), 6.25 (d, J = 10.9 Hz, 1 H), 6.20 (d, J = 10.9 Hz, 1 H), 6.02 (app t, J = 2.1 Hz, 1 H), 5.99 (app t, J = 2.1 Hz, 1 H). ¹³C NMR (151 MHz, CDCl₃): δ = 140.4, 140.3, 137.4, 136.1, 134.1, 130.31, 130.27, 129.2, 128.6, 128.44, 128.37, 127.6, 105.5, 105.4, 68.7, 68.0. NMR data for the anti isomer: ¹H NMR (600 MHz, CDCl₃): δ = 7.49–7.47 (m, 2 H), 7.44–7.41 (m, 2 H), 7.37–7.35 (m, 2 H), 7.31 (app d, J = 2.3 Hz, 2 H), 7.22–7.17 (m, 3 H), 7.16–7.13 (m, 2 H), 6.36 (d, J = 10.9 Hz, 1 H), 6.31 (d, J = 10.9 Hz, 1 H), 6.04 (app dt, J = 4.0, 2.1 Hz, 2 H). ¹³C NMR (151 MHz, CDCl₃): δ = 140.1, 140.0, 136.6, 135.4, 134.2, 130.6, 130.5, 129.9, 128.67, 128.65, 128.5, 105.11, 105.05, 68.9, 68.2. HRMS (ESI-TOF): m/z [M + Na]⁺ calcd for C₂₀H₁₇ ³⁵ClN₄Na: 371.1034; found: 371.1030; m/z [M + Na]⁺ calcd for C₂₀H₁₇ ³⁷ClN₄Na: 373.1004; found: 373.1000.