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TCI Practical Example: Reductive C-N Cross-coupling Reaction using an Organophosphorus Catalyst

We are proud to present the synthesis of a secondary arylamine by the reductive C-N cross coupling reaction of a nitroarene and an arylboronic acid using anti-1,2,2,3,4,4-hexamethylphosphetane 1-oxide as an organocatalyst.

Used Chemicals

• 1-Bromo-2-nitrobenzene [B0622]
• Phenylboronic Acid [B0857]
• anti-1,2,2,3,4,4-Hexamethylphosphetane 1-Oxide [H1766]
• Phenylsilane [P1291]
• CPME [M1698]

Procedure

To a 3-necked 50 mL flask was charged with 1-bromo-2-nitrobenzene (2.006 g, 9.931 mmol, 1.0 equiv.), phenylboronic acid (1.332 g, 10.92 mmol, 1.1 equiv.) and anti-1,2,2,3,4,4-hexamethylphosphetane 1-oxide (0.259 g, 1.49 mmol, 0.15 equiv.). The flask was evacuated on a Schlenk line, and backfilled with argon (3 times). The flask was then charged dry CPME (20 mL), followed by phenylsilane (2.4 mL, 20 mmol, 2.0 equiv.). The mixture was then heated to reflux and stirred for 4 h. The reaction mixture was cooled to room temperature and washed with 1 mol/L NaOH aqueous solution (40 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (20 mL). The combined organic layers were washed with brine (20 mL), dried over Na₂SO₄ and filtered. The solvent was removed under reduced pressure. The residue was purified by column chromatography (eluent: dichloromethane/ethyl acetate/hexane, 20/1/79) to obtain 1 as a white solid (2.20 g, 89.3%).

Experimenter's Comments

The reaction mixture was monitored by GC.
CPME was dried over MS4A before use.

Analytical Data

Compound 1

¹H NMR (400 MHz, CDCl₃); δ 7.54 (dd, J = 7.8, 1.4 Hz, 1H), 7.32–7.36 (m, 2H), 7.26–7.28 (m, 1H), 7.16–7.18 (m, 3H), 7.06 (t, J = 7.3 Hz), 6.75 (ddd, J = 7.8, 7.3, 1.4 Hz), 5.79 (brs, 1H).

¹³C NMR (101 MHz, CDCl₃); δ 141.7, 141.5, 133.1, 129.6, 128.2, 122.8, 121.0, 120.4, 115.9, 112.3.

Lead Reference

• An Improved P^III/P^V=O-Catalyzed Reductive C–N Coupling of Nitroaromatics and Boronic Acids by Mechanistic Differentiation of Rate- and Product-Determining Steps
  • G. Li, T. V. Nykaza, J. C. Cooper, A. Ramirez, M. R. Luzung, A. T. Radosevich, J. Am. Chem. Soc. 2020, 142, 6786.

Other References

• Intermolecular Reductive C–N Cross Coupling of Nitroarenes and Boronic Acids by P^III/P^V=O Catalysis
  • T. V. Nykaza, J. C. Cooper, G. Li, N. Mahieu, A. Ramirez, M. R. Luzung, A. T. Radosevich, J. Am. Chem. Soc. 2018, 140, 15200.