Cu(OAc)₂ (HPMC encapsulated)

• Phenylboronic Acid [B0857]
• 1-Boc-piperazine [B2415]
• Cesium Carbonate [C2160]
• Cu(OAc)₂ (HPMC encapsulated) [R0312]
• Methanol
• Pyridine

Under oxygen atmosphere, copper(II) acetate (HPMC encapsulated) (one capsule) was added to a solution of phenylboronic acid (37 mg, 300 µmol), 1-Boc-piperazine (220 mg, 1.2 mmol, 4.0 eq.) and cesium carbonate (98 mg, 300 µmol, 1.0 eq.) in methanol (2.0 mL) and pyridine (0.50 mL) at room temperature and the reaction mixture was stirred at 55 °C for 18 hours. After cooling to room temperature, the solution was diluted with ethyl acetate (15 mL) and sat. Na₂SO₄ aq. (15 mL), and filtered through Celite pad. The filtrate was extracted with ethyl acetate (15 mL x 2) and the organic layer was washed with 2 mol/L HCl (15 mL) and sat. NaHCO₃ aq. (15 mL), dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (ethyl acetate:hexane = 0:1 - 1:6) to afford 1-Boc-4-phenylpiperazine (24 mg, 30% yield) as a yellow solid.

The reaction mixture was monitored by UPLC.
The capsule has the shape shown in Fig. 1 and copper(II) acetate (ca. 600 μmol) is encapsulated in each capsule, respectively.

Fig. 1. Appearance of capsule

Fig. 2. Capsule disintegrating
(left) Immediately after the addition of the capsule,
(right) 15 minutes after the addition of the capsule.

1-Boc-4-phenylpiperazine

¹H NMR (400 MHz, CDCl₃); δ 7.20 (t, J = 8.0 Hz, 2H), 6.87-6.80 (m, 3H), 3.51 (t, J = 7.2 Hz, 2H), 3.05 (t, J = 7.2 Hz, 2H), 1.41 (s, 9H).

• Mediator-Enabled Electrocatalysis with Ligandless Copper for Anaerobic Chan–Lam Coupling Reactions.
  • B. R. Walker, S. Manabe, A. T. Brusoe, C. S. Sevov, J. Am. Chem. Soc. 2021, 143, 6257.