Copper Salt Catalyzed Coupling of Organobismuth Reagents and Azo Compounds

Abstract

A new copper salt catalyzed C-N coupling is described. This smooth reaction between azo compounds and organobismuth reagents provides efficient and highly regioselective access to Boc-protected aryl hydrazines. The yields under optimized conditions are mostly excellent and the synthetic procedure is robust and simple.

azo compounds - catalysis - cross-coupling - organobismuth compounds - transition metals

References and Notes

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14

Typical Procedure (Table [2] , entry 2): A two-neck flask, equipped with a reflux condenser, was charged with PhN=NBoc (87 mg, 0.378 mmol) and Ph₃Bi (200 mg, 1.2 equiv), evacuated, and backfilled with argon. Then MeCN (2 mL) and MeOH (76 µL, 5 equiv) were added, followed by Cu(OAc)₂·H₂O (8 mg, 0.1 equiv). The flask was immersed in a bath with the temperature maintained at 70 °C. The reaction was monitored by TLC (EtOAc-hexane, 1:4) and was complete in 5 min. The solvent was evaporated in vacuo, the residue was chromatographed with CHCl₃-hexane (1:1) to remove nonpolar compounds and then EtOAc-hexane (1:2) to yield 105 mg of pure product (90%), by TLC and NMR.
White crystals (from hexane); mp 122-123.5 °C. IR (KBr): 3317 (NH), 1704 (CO) cm^-1. ¹H NMR (CDCl₃): δ = 1.48/1.31 (s, 9 H, Boc), 6.87/6.71 (br s, 1 H, NH), 6.9-7.4 (m, 10 H, Ph). ¹³C NMR (CDCl₃): δ = 28.3 (Boc), 81.3 (C_q, Boc), 119.4, 122.7, 129.1, 146.4 (Ph), 155.3 (CO, Boc).

15

Structures of all compounds prepared were confirmed with the help of spectral and analytical data. Analytical samples were obtained by crystallization. NMR spectra were mea-sured in CDCl₃. Chemical shifts of conformers are given in decreasing order of intensity and separated by slashes.
4-NO ₂ C₆H₄( o -Tol)NNHBoc ( 2c). IR (KBr): 3306 (NH), 1706 (CO) cm^-1. Orange-brown semi-solid. ¹H NMR: δ = 1.46 (9 H, Boc), 2.20 (3 H, CH₃C₆H₄), 6.61 (d, 2 H, 4-NO₂C₆H₄), 7.16-7.46 (m, 5 H, o-Tol, NH), 8.05 (d, 2 H, 4-NO₂ C₆H₄). ¹³C NMR: δ = 28.2 (Boc), 82.1 (C_q, Boc), 111.7, 125.8, 127.7, 128.6, 131.6, 140.0, 141.6, 153.0 (Ar), 154.6 (CO, Boc). Anal. Calcd for C₁₈H₂₁N₃O₄: N, 12.24; C, 62.96; H, 6.16. Found: N, 11.89; C, 62.61; H, 6.01.
2,4-(NO₂)₂C₆H₃ ( o -Tol)NNHBoc ( 3b). Yellowish-brown liquid. IR (KBr): 3441, 3290 (NH), 1731, 1703, 1685 (CO) cm^-1. ¹H NMR: δ = 1.44 (s, 9 H, Boc), 2.20 (s, 3 H, CH₃C₆H₄), 6.84-7.47 [m, 6 H, o-Tol, NH, 2,4-(NO₂)₂C₆H₃], 8.20 [d, J _HH = 9 Hz, 1 H, 2,4-(NO₂)₂C₆H₃], 8.56 [d, J _HH = 2.6 Hz, 1 H, 2,4-(NO₂)₂C₆H₃]. ¹³C NMR: δ = 28.1 (Boc), 82.7 (C_q, Boc), 119.5, 122.5, 125.8, 127.6, 128.0, 128.6, 131.9, 134.2, 137.8, 139.9, 141.8, 146.4 (Ar), 154.0 (CO, Boc).
Ph( o -Tol)NNHBoc ( 4a). White solid; mp 129-130.5 °C (hexane-EtOAc). IR (KBr): 3277 (NH), 1700 (CO) cm^-1. ¹H NMR: δ = 1.43 (s, 9 H, Boc), 2.20 (s, 3 H, CH₃C₆H₄), 6.62-7.32 (m, 10 H, Ph, o-Tol, NH). ¹³C NMR: δ = 18.1 (CH₃C₆H₄), 28.2 (Boc), 81.0 (C_q, Boc), 113.5, 119.6, 126.8, 127.1, 128.9, 131.1, 135.7, 143.7, 147.8 (Ar), 154.9 (CO, Boc). Anal. Calcd for C₁₈H₂₂N₂O₂: N, 9.39; C, 72.46; H, 7.43. Found: N, 9.29; C, 71.93; H, 7.42.
o -Tol(Naphthyl)NNHBoc ( 4b). Slightly brown solid; mp 111.5-113.5 °C(hexane). IR (KBr): 3256 (NH), 1687 (CO) cm^-1. ¹H NMR: δ = 1.43/1.31 (s, 9 H, Boc), 2.10 (s, 3 H, CH₃C₆H₄), 6.70-8.29 (m, 12 H, o-Tol, 1-Naphthyl, NH). ¹³C NMR: δ = 18.6 (CH₃C₆H₄), 28.2 (Boc), 80.5 (C_q, Boc), 118.7, 120.5, 121.2, 124.0, 124.3, 125.2, 125.7, 126.0, 126.3, 128.0, 128.8, 131.4, 131.8, 134.8, 144.6, 147.1 (Ar), 154.1 (CO, Boc). Anal. Calcd for C₂₂H₂₄N₂O₂: N, 8.04; C, 75.83; H, 6.94. Found: N, 8.04; C, 75.62; H, 7.00.
(o -Tol) ₂ NNHBoc ( 4c). White solid; mp 107.5-109 °C (hexane). IR (KBr): 3272 (NH), 1700 (CO) cm^-1. ¹H NMR: δ = 1.43/1.29 (s, 9 H, Boc), 2.12/2.09 (s, 6 H, 2 × CH₃C₆H₄), 6.61 (s, 1 H, NH), 6.7-7.1 (m, 8 H, 2 × C₆H₄). ¹³C NMR: δ = 18.5 (CH₃C₆H₄), 28.2 (Boc), 80.3/81.0 (C_q, Boc), 121.2, 124.1, 126.2, 131.3, 132.1, 146.4 (C₆H₄), 154.0/155.7 (CO, Boc). Anal. Calcd for C₁₉H₂₄N₂O₂: N, 8.97; C, 73.05; H, 7.74. Found: N, 8.95; C, 72.95; H, 7.92.

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