Products > TCI Topics Archives > TCI Topics 2024 >

TCI Practical Example: The Intermolecular Hydroamination of the Unactivated Alkene Using a Photoredox Catalyst

We are proud to present the intermolecular hydroamination of 4-methoxystyrene and piperidine catalyzed by Ir[dF(Me)(ppy)₂(dtbbpy)]PF₆ as a photoredox catalyst.

Used Chemicals

• Piperidine
• 4-Methoxystyrene [M0130]
• (4,4'-Di-tert-butyl-2,2'-bipyridine)bis[2-(2',4'-difluorophenyl)-5-methylpyridine]iridium(III) Hexafluorophosphate (= Ir[dF(Me)(ppy)₂(dtbbpy)]PF₆) [B6254]
• 2,4,6-Triisopropylbenzenethiol
• Toluene

Procedure

2,4,6-Triisopropylbenzenethiol (0.060 g, 0.25 mmol, 0.5 eq), piperidine (0.050 mL, 0.50 mmol, 1.0 eq), 4-methoxystyrene (0.10 mL, 0.75mmol, 1.5 eq), Ir[dF(Me)(ppy)₂(dtbbpy)]PF₆ (10 mg, 0.0099 mmol, 2.0 mol%) were dissolved in toluene (10 mL) at room temperature under nitrogen gas. The mixture was placed at a distance of 2-3 cm from blue LED lamps with a cooling fan. The yellow orange suspension was stirred at room temperature under visible light irradiation until the amine was completely consumed. After 12 hours of irradiation, the reaction mixture was diluted with ethyl acetate (20 mL) and extracted with 1 mol/L HCl aq. (70 mL x 2). The combined aqueous layer was washed with diethyl ether (30 mL x 2), then neutralized with 2 mol/L NaOH aq. (78 mL) to pH 7 and then saturated sodium bicarbonate aq. (10 mL) was added to ensure a slightly basic condition. The aqueous layer was extracted with dichloromethane (50 mL x 3) and the combined organic layer was dried over sodium sulfate (30 g) and filtered. The solvent was removed in vacuo to give compound 1 as a colorless oil (39 mg, 35% yield).

Experimenter’s Comments

• Toluene was degassed with nitrogen for 30 minutes before use.
• Irradiation of visible light was performed with Kessil A160WE Tuna Blue 40W x 2.
• The reaction mixture was maintained at rt by a cooling fan.
• The reaction mixture was monitored by ¹NMR and GC.

Analytical Data

Compound 1

¹H NMR (400 MHz, CDCl₃); δ 7.12 (d, J = 7.8 Hz, 2H), 6.82 (d, J = 7.8 Hz, 2H), 3.78 (s, 3H), 2.79–2.75 (m, 2H), 2.56–2.49 (m, 6H), 1.46 (m, 4H), 1.25 (bs, 2H).

¹³C NMR (101 MHz, CDCl₃); δ 157.82, 132.58, 129.57, 113.75, 61.64, 55.22, 54.51, 32.62, 25.90, 24.37.

Lead Reference

• Catalytic intermolecular hydroaminations of unactivated olefins with secondary alkyl amines
  • A. J. Musacchio, B. C. Lainhart, X. Zhang, S. G. Naguib, T. C. Sherwood, R. R. Knowles, Science 2017, 355, 727.

Other References

• Anti-Markovnikov Hydroamination of Unactivated Alkenes with Primary Alkyl Amines
  • D. C. Miller, J. M. Ganley, A. J. Musacchio, T. C. Sherwood, W. R. Ewing, R. R. Knowles, J. Am. Chem. Soc. 2019, 141, 16590.