Aryl Norbornanes and Analogues via Palladium-Catalyzed Hydroarylation with Arenediazonium Tetrafluoroborates

Abstract

The palladium-catalyzed hydroarylation of arenediazonium tetrafluoroborates with norbornene derivatives and analogues in the presence of Pd(OAc)₂ and i-Pr₃SiH in THF affords hydroarylation products containing the added aryl unit in the exo position in good to high yields. The reaction tolerates a variety of useful functional groups and can be performed as a one-pot procedure generating the arenediazonium salt in situ.

Key words

norbornene - palladium - hydroarylation - arenediazonium salts

References and Notes

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16

When 1a was subjected to the reaction conditions reported in Table  [¹] (entry 5) omitting Pd(OAc)₂ no reduction product 4 was formed suggesting that the reduction of 1a to 4 proceeds through a palladium-catalyzed process.

17

Typical Procedure for the Palladium-Catalyzed Hydro-arylation of Norbornene Derivatives with Arenediazo-nium Tetrafluoroborates - Hydroarylation of 1a with 2a (Table 2, entry 1)
To a stirred solution of 1a (105.1 mg, 0.50 mmol) and Pd(OAc)₂ (5.6 mg, 0.025 mmol) in anhyd THF (4.0 mL), 2a (233.8 mg, 1.0 mmol) was added at r.t. under argon. The reaction mixture was cooled in an ice bath. Then, i-Pr₃SiH (205 µL, 1.0 mmol) was added and the reaction mixture was stirred at 15 ˚C for 40 min under argon (the reactor was protected from light with aluminum film). After this time, the mixture was diluted with EtOAc, washed with H₂O, dried over Na₂SO₄, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel [n-hexane-EtOAc, 90:10 (v/v)] to afford 120.8 mg (73% yield) of 3a, mp 64-66 ˚C. IR (KBr): 2968, 1735, 1198 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.89 (d, J = 8.2 Hz, 2 H), 7.38 (d, J = 8.2 Hz, 2 H), 3.70 (s, 6 H), 3.64 (t, J = 7.4 Hz, 1 H), 3.19 (ddd, J ₁ = 11.7 Hz, J ₂ = 4.5 Hz, J ₃ = 1.4 Hz, 1 H), 2.99 (dd, J ₁ = 11.8 Hz, J ₂ = 3.7 Hz, 1 H), 2.75-270 (m, 1 H), 2.73-2.58 (m, 1 H), 2.13 (ddd, J ₁ = 11.1 Hz, J ₂ = 8.8 Hz, J ₃ = 3.7 Hz, 1 H), 1.74-1.65 (m, 2 H), 1.42-1.26 (m, 1 H). ^¹³C NMR (100.6 MHz, CDCl₃): δ = 197.9, 172.9, 172.6, 151.9, 134.9, 128.5, 127.5, 51.7, 51.5, 47.7, 46.2, 45.9, 41.6, 40.2, 37.5, 33.2, 26.6. MS: m/z (relative intensity) = 330 (12) [M⁺], 298 (10), 270 (57), 185 (232), 43 (100).

18

NOESY experiments on 3a: for selected H-H interactions, see Figure  [²] .

Figure 2

20

Palladium-Catalyzed Hydroarylation of 1a with 2a Generated In Situ
A solution of BF₃˙OEt₂ (140 µL, 1.1 mmol) in anhyd THF (1 mL) was cooled at -15 ˚C and p-aminoacetophenone (135.1 mg, 1 mmol) was added. Then, tert-butyl nitrite (160 µL, 1.3 mmol) in 1 mL of the same solvent was added dropwise to the rapidly stirred reaction solution over a period of 10 min. Following complete addition, the temperature of the solution was maintained at -15 ˚C for 10 min and subsequently allowed to warm to 5 ˚C in an ice-water bath over a period of 20 min. Then, the reaction mixture was warmed to r.t. and stirred at the same temperature till the starting p-amino-acetophenone was converted into p-acetylbenzenediazo-nium tetrafluoroborate. The reaction mixture was cooled in an ice bath and 1a (105.1 mg, 0.50 mmol), Pd(OAc)₂ (5.6 mg, 0.025 mmol), i-Pr₃SiH (205 µL, 1.0 mmol), and of anhyd THF (2 mL) were added. The reaction mixture was allowed to warm to 20 ˚C and stirred at that temperature for 6 h under argon (the reactor was protected from light with aluminum film). After this time, the mixture was diluted with EtOAc, washed with H₂O, dried over Na₂SO₄, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel [n-hexane-EtOAc, 90:10 (v/v)] to afford 106.3 mg (64% yield) of 3a.