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Synlett 2008(16): 2508-2512  
DOI: 10.1055/s-2008-1078051
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

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

Gabriele Bartoli, Sandro Cacchi*, Giancarlo Fabrizi, Antonella Goggiamani
Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi ‘La Sapienza’, P. le A. Moro 5, 00185 Rome, Italy
Fax: +39(06)49912780; e-Mail: sandro.cacchi@uniroma1.it;
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Publication History

Received 18 June 2008
Publication Date:
12 September 2008 (online)

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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

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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.