An Efficient Oxidative Cross-Coupling Reaction between C–H and N–H Bonds; A Transition-Metal-Free Protocol at Room Temperature

Abstract

A transition-metal-free oxidative coupling of allylic C–H and heterocyclic/aromatic N–H bonds was performed under mild conditions. Promoted by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), up to 99% yield could be achieved.

Key words

metal-free - cross-coupling - oxidative coupling - amination - C–H activation

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• 19 Analytical data of product 3a: ¹H NMR (400 MHz, CDCl₃): δ = 7.61 (d, J = 1.6 Hz, 1 H), 7.48 (d, J = 2.0 Hz, 1 H), 7.41–7.23 (m, 10 H), 6.73 (dd, J = 7.0, 15.8 Hz, 1 H), 6.45 (d, J = 16.0 Hz, 1 H), 6.32 (t, J = 2.0 Hz, 1 H), 6.20 (d, J = 7.2 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 139.8, 139.6, 136.2, 133.9, 128.9, 128.74, 128.67, 128.29, 128.27, 127.54, 127.48, 126.9, 105.8, 67.7. IR: 3060, 3028, 1508, 1495, 1450, 1395, 1280, 1088, 1046, 748, 695 cm^–1. HRMS: m/z [M+Na]⁺ calcd for C₁₈H₁₆N₂Na: 283.1211; found: 283.1198.
• 20 Analytical data of product 3c: ¹H NMR (400 MHz, CDCl₃): δ = 8.01 (s, 1 H), 7.77 (d, J = 8.0 Hz, 1 H), 7.66 (d, J = 8.4 Hz, 1 H), 7.45 (d, J = 6.8 Hz, 2 H), 7.41–7.38 (m, 2 H), 7.37–7.34 (m, 2 H), 7.33–7.30 (m, 3 H), 7.12 (dd, J = 3.0, 8.2 Hz, 1 H), 6.88 (dd, J = 7.0, 15.8 Hz, 1 H), 6.56 (d, J = 16.4 Hz, 1 H), 6.52 (d, J = 6.8 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 149.0, 139.0, 136.0, 134.6, 129.0, 128.8, 128.5, 128.4, 127.6, 127.0, 126.9, 126.1, 122.3, 121.9, 121.8, 120.4, 117.9, 69.3. IR: 3059, 3028, 1627, 1513, 1495, 1451, 1390, 1152, 1134, 967, 756, 695 cm^–1 .
• 21 Analytical data of product 5a: ¹H NMR (400 MHz, CDCl₃): δ = 7.45 (d, J = 8.8 Hz, 2 H), 7.39–7.36 (m, 4 H), 7.32–7.29 (m, 3 H), 7.25–7.22 (m, 1 H), 7.17–7.13 (m, 2 H), 6.72 (t, J = 7.4 Hz, 1 H), 6.66–6.62 (m, 3 H), 6.41 (dd, J = 6.2, 15.8 Hz, 1 H), 5.10 (d, J = 6.0 Hz, 1 H), 4.13 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 147.4, 142.2, 136.8, 131.2, 130.9, 129.3, 129.0, 128.7, 127.8, 127.7, 127.4, 126.7, 117.9, 113.8, 60.8. IR: 3407, 3055, 3025, 1601, 1502, 1449, 1314, 1261, 968, 747, 692 cm^–1. HRMS: m/z [M – H]⁺ calcd for C₂₁H₁₈N: 284.1439; found: 284.1426.
• 22 Analytical data of (E)-1,3-diphenylprop-2-en-1-amine: ¹H NMR (400 MHz, CDCl₃): δ = 7.46–7.36 (m, 6 H), 7.33–7.28 (m, 3 H), 7.25–7.21 (m, 1 H), 6.61 (dd, J = 3.8, 15.8 Hz, 1 H), 6.41–6.30 (m, 1 H), 5.11 (t, J = 7.6 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 141.4, 141.3, 136.8, 131.7, 131.5, 130.6, 130.5, 128.7, 127.9, 127.8, 127.2, 126.8, 79.4, 79.3.
• 23 Unless otherwise noted, the reaction was carried out as following: To a solution of 1, 4-dioxane (1.0 mL) was added 1,3-diphenylpropenes 1 (0.1 mmol), nitrogen-based nucleophile 2 or 4 (0.12 mmol) and oxidant (0.14 mmol). The reaction mixture was stirred at r.t. for 2–5 h and then the solvent was removed under vacuum. The residue was purified by column chromatography on silica gel to yield the desired product.