A Late-Stage Strategy for the Functionalization of Triazolium-Based NHC Catalysts

Abstract

A strategy for the diversification of triazolium-based catalysts is presented. This method is based on the reduction to the triazoline, which serves as a suitable and stable substrate for palladium-mediated cross-coupling, followed by trityl cation mediated reoxidation to the triazolium.

Key words

NHC Catalysis - organocatalysis - asymmetric catalysis

• References and Notes


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• 17 Typical Experimental Procedure – Synthesis of 5a In a glove box, a dry 2-dram glass vial was loaded with PdCl₂(PPh₃)₂ (7 mg, 0.01 mmol, 0.05 equiv). The vial was sealed and removed from the glove box. To this vial was added triazoline (100 mg, 0.22 mmol, 1 equiv), phenylboronic acid (0.32 mmol, 1.5 equiv), and potassium phosphate tribasic (93 mg, 0.44 mmol, 2 equiv). Anhydrous THF (1.5 mL) was added followed by H₂O (0.5 mL), as well as a magnetic stir bar. The vial was sealed, secured with Teflon tape, and heated by oil bath at 60 °C for 6 h. Reaction was deemed complete by TLC. The reaction was cooled to r.t. and brine (1 mL) and EtOAc (1 mL) was added to the reaction. The aqueous fraction was removed, and the organic layer was dried over MgSO₄. The crude reaction product was filtered and concentrated. The crude product was purified by flash column chromatography, eluting with 0–50% EtOAc–hexanes through basic alumina, and 60 mg of dark brown solid was isolated (60% yield). R_f  = 0.5 (50% EtOAc–hexane). ¹H NMR (300 MHz, acetone-d ₆): δ = 7.70–7.60 (m, 4 H), 7.47–7.35 (m, 4 H), 5.68–5.67 (m, 1 H), 5.04 (t, J = 1.1 Hz, 1 H), 4.78 (dd, J = 5.6, 1.1 Hz, 1 H), 4.64–4.55 (m, 2 H), 4.47 (d, J = 15.6 Hz, 1 H), 3.30–3.28 (m, 2 H). ¹³C NMR (101 MHz, acetone-d ₆): δ = 149.0, 141.6, 140.9, 140.3, 139.6, 129.82, 129.73, 128.49, 128.44, 128.38, 127.8, 127.25, 127.18, 127.16, 126.8, 125.6, 123.8, 123.2, 77.1, 73.6, 62.3, 59.2, 34.8. MS: m/z calcd for C₂₄H₁₆F₅N₃O: 457.4; found: 458.1 [M + H]. IR (neat): 2914, 1626, 1504, 1479, 1429, 1340, 1307, 1055, 1039, 977 cm^–1. [α]_D ²³ –39.17 (c 2.4, acetone).