S_NAr-Derived Decomposition By-products Involving Pentafluorophenyl Triazolium Carbenes

Abstract

Pentafluorophenyl triazolium carbenes, widely used in NHC catalysis, can decompose by several mechanisms. Under high concentration conditions, the azolium may undergo a pentafluorophenyl exchange by a proposed S_NAr mechanism to give an inactive salt. In the presence of appropriate substrates, cyclization on the ­ortho-position of the arene can occur, also by S_NAr. These adducts provide a potential pathway for catalyst decomposition and serve as a caveat to the development of new reactions and catalysts.

Key words

pentafluorophenyl N-heterocyclic carbene - inner salt - spirocyclic oxindole - decomposition

• References and Notes

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• 9 Typical Experimental Procedure for Decomposition of 1: In a 5-mL vial were subsequently added triazolium salt 1 (0.2 mmol), KOAc (0.2 mmol) and MeOH (3 mL). The solution was stirred under argon at 23 °C for 16 h, and then concentrated. The resulting residue was purified by column chromatography on silica gel [eluent: hexanes–EtOAc (1:1) then 100% EtOAc then 100% MeOH] to give 2 and 3. The salt 3 can be further purified by trituration with EtOAc. Compound 2: yellow solid. ¹H NMR (300 MHz, CDCl₃): δ = 8.26 (d, J = 12.5 Hz, 1 H), 7.30 (br s, 4 H), 7.00 (br s, 0.5 H), 6.31 (br s, 0.5 H), 4.71–4.74 (m, 1 H), 4.63 (t, J = 4.7 Hz, 1 H), 4.21–4.38 (m, 2 H), 3.26 (dd, J = 16.9, 5.1 Hz, 1 H), 3.12 (d, J = 16.9 Hz, 1 H). ¹³C{¹H} NMR (75 MHz, CDCl₃): δ = 163.8, 158.5, 139.3, 128.7, 128.4, 127.4, 125.3, 123.3, 64.3, 57.2, 37.9, 29.3. ¹⁹F NMR (282 MHz, CDCl₃): δ = –142.8 (s, 0.5 F), –143.2 (s, 0.5 F), –145.8 (d, J = 19.8 Hz, 1 F), –152.6 (t, J = 21.4 Hz, 0.5 F), –153.4 (t, J = 21.4 Hz, 0.5 F), –160.8 (t, J = 19.5 Hz, 1 F), –161.5 (s, 1 F). LRMS (ES+): m/z [M]⁺ calcd for C₁₈H₁₂F₅N₃O₂: 397.09; found: 398.10. Compound 3: slightly yellow solid. ¹H NMR (400 MHz, CDCl₃): δ = 13.23 (s, 1 H), 7.71 (d, J = 7.5 Hz, 1 H), 7.23–7.33 (m, 3 H), 6.50 (br s, 1 H), 4.98–5.05 (m, 3 H), 3.32 (dd, J = 4.2, 17.1 Hz, 1 H), 3.19 (d, J = 17.1 Hz, 1 H). ¹³C{¹H} NMR (101 MHz, CDCl₃): δ = 150.6, 148.1 (br), 139.8, 134.7, 129.7, 128.0, 125.4, 124.2, 77.5, 62.8, 60.3, 37.5. ¹⁹F NMR (282 MHz, CDCl₃): δ = –143.7 (d, J = 18.4 Hz, 2 F), –145.7 (t, J = 21.8 Hz, 1 F), –157.9 to –158.1 (m, 2 F). HRMS (ESI): m/z [M – OH]⁺ calcd for C₁₈H₁₁F₅N₃O: 380.0817; found: 380.0816.
• 10 Salt 3 proved difficult to purify to analytically pure material, resulting in significant loss of material. Thus, we do not report an isolated yield here.
• 11 Compound 4: orange solid. ¹H NMR (300 MHz, CDCl₃): δ = 7.35 (d, J = 4.1 Hz, 2 H), 7.13–7.17 (m, 1 H), 6.71 (d, J = 7.8 Hz, 1 H), 6.01 (t, J = 3.5 Hz, 1 H), 5.05–5.17 (m, 3 H), 3.43 (dd, J = 17.0, 4.5 Hz, 1 H), 3.34 (d, J = 17.0 Hz, 1 H), 1.86–1.62 (br s, 2 H from H₂O). ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 150.7, 139.7, 134.4, 130.3, 128.6, 126.0, 123.8, 98.7, 77.8, 62.9, 62.8, 60.1, 36.9. ¹⁹F NMR (376 MHz, CDCl₃): δ = –142.3 to –142.4 (m, 1 F), –144.1 (tt, J = 21.6, 4.4 Hz, 1 F), –144.2 to –144.3 (m, 1 F), –144.6 to –144.7 (m, 1 F), –147.3 to –147.4 (m, 1 F), –156.5 (td, J = 21.8, 6.8 Hz, 1 F), –156.8 (td, J = 21.8, 6.8 Hz, 1 F), –163.2 (t, J = 23.0 Hz, 1 F), –163.5 (t, J = 23.0 Hz, 1 F). HRMS (ESI): m/z [M + H]⁺ calcd for C₂₄H₁₁F₉N₃O₂: 544.0708; found: 544.0712.
• 12 This structure is somewhat disordered with what appears to be partial protonation of the phenolic oxygen. There is a corresponding counterion, also disordered, whose identity could not be determined (hydroxide vs. fluoride). Both structures (4 and 9) have been submitted to the Cambridge Crystallographic Data Centre as CCDC 935024 and CCDC 935025.
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• 15 Experimental Procedure for the Formation of 9: In a 5-mL vial were subsequently added triazolium salt 8 (0.05 mmol), 7 (0.05 mmol), K₂CO₃ (0.05 mmol) and THF (4 mL). The vial was capped. The mixture was stirred at 23 °C for 48 h, and then concentrated. The resulting residue was purified by preparative TLC [eluent: hexanes–EtOAc (1:1)] to give the adduct 9 as a solid. Compound 9: slightly yellow solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.81 (d, J = 8.2 Hz, 1 H), 7.25 (td, J = 2.4, 8.3 Hz, 1 H), 7.01–7.07 (m, 2 H), 4.22–4.33 (m, 2 H), 3.34 (s, 3 H), 2.88–2.92 (m, 2 H), 2.54 (p, J = 7.5 Hz, 2 H), 1.64 (s, 9 H). ¹³C{¹H} NMR (101 MHz, CDCl₃): δ = 177.2, 164.6, 158.8, 158.7, 149.5, 145.5, 138.7, 134.5, 128.7, 124.7, 123.8, 114.5, 109.9, 84.0, 50.2, 49.3, 28.1, 26.2, 21.2. ¹⁹F NMR (282 MHz, CDCl₃): δ = –134.9 (ddd, J = 5.3, 8.8, 22.5 Hz, 1 F), –150.7 (dd, J = 9.0, 20.5 Hz, 1 F), –153.87 (dt, J = 5.1, 21.0 Hz, 1 F), –160.43 (t, J = 22.0 Hz, 1 F). HRMS (ESI): m/z [M + H]⁺ calcd for C₂₇H₂₃F₄N₄O₅: 559.1599; found: 559.1603.
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• 17 A catalyst deactivation pathway has been observed for N-phenyl triazolium precursors, see: Hao L, Du Y, Lv H, Chen X, Jiang H, Shao Y, Chi YR. Org. Lett. 2012; 14: 2154