1148
R. K. Arvela, N. E. Leadbeater
LETTER
Microwave reactions were conducted using a CEM Discover™
Synthesis Unit (CEM Corp., Matthews, NC). The machine consists
of a continuous focused microwave power delivery system with op-
erator selectable power output from 0–300 W. Reactions were per-
formed in glass vessels (capacity 10 mL) sealed with a septum. The
pressure is controlled by a load cell connected to the vessel via a 14-
gauge needle, which penetrates just below the septum surface. The
temperature of the contents of the vessel was monitored using a cal-
ibrated infrared temperature control mounted under the reaction
vessel. All experiments were performed using a stirring option
whereby the contents of the vessel are stirred by means of a rotating
magnetic plate located below the floor of the microwave cavity and
a Teflon-coated magnetic stir bar in the vessel.
References
(1) Metal-Catalysed Cross-Coupling Reactions; Diederich, F.;
Stang, P. J., Eds.; Wiley-VCH: New York, 1998.
(2) For recent reviews see: (a) Hassan, J.; Sévignon, M.; Gozzi,
C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359.
(b) Suzuki, A. J. Organomet. Chem. 1999, 576, 147.
(c) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(3) See for example: Kashiyama, E.; Hutchinson, I.; Chua, M.-
S.; Stinson, S. F.; Phillips, L. R.; Kaur, G.; Sauville, E. A.;
Bradshaw, T. D.; Westwell, A. D.; Stevens, M. F. G. J. Med.
Chem. 1999, 42, 4172.
(4) Leadbeater, N. E.; Marco, M. Org. Lett. 2002, 4, 2973.
(5) Leadbeater, N. E.; Marco, M. J. Org. Chem. 2003, 68, 888.
(6) Bacon, R. G. R.; Hill, H. A. O. J. Chem. Soc. 1964, 1097.
(7) Clark, J. H.; Denness, J. E.; McClinton, M. A.; Wynd, A. J.
J. Fluorine Chem. 1990, 50, 411.
General Procedure (Microwave Heating): In a 10 mL glass tube
was placed aryl halide (1.0 mmol), nickel salt, 0.5 mL DMF and a
magnetic stirring bar. Reactions using NiBr2 were performed using
2 equiv of the nickel salt. Those involving NiCl2 can be run using 1
equiv of the nickel salt. The vessel was sealed with a septum and
placed into the microwave cavity. Microwave irradiation of 100 W
was used, the temperature being ramped from r.t. to 170 ºC. Once
this temperature was reached, the reaction mixture was held at this
temperature for 5 min. After allowing the mixture to cool to r.t., the
reaction vessel was opened and the contents poured into a separat-
ing funnel and the tube washed with water and then with diethyl
ether, these washings being added to the separating funnel. Further
water and diethyl ether (20 mL of each) were added and the organic
material extracted and removed. After further extraction of the
aqueous layer with diethyl ether, combining the organic washings
and drying them over MgSO4, the diethyl ether was removed in-
vacuuo leaving the crude product. In optimizing experiments the
1H-NMR spectrum of the product mixture was recorded and the
product yield determined by reference to a known quantity of an in-
ternal standard. In the screening experiments, the products were
characterised by comparison of 1H-and 13C-NMR spectra with those
of authentic samples and yields were determined by NMR with
reference to a known quantity of an internal standard. This method
was used to quantify the product because because these are equilib-
rium reactions and we found it to be non-trivial on a small scale to
separate simple aryl halide products from the corresponding aryl
halide starting materials.
(8) Bozell, J. J.; Vogt, C. E. J. Am. Chem. Soc. 1988, 110, 2655.
(9) Yang, S. H.; Li, C. S.; Cheng, C. H. J. Org. Chem. 1987, 52,
691.
(10) Takagi, K.; Hayama, N.; Inokawa, S. Bull. Chem. Soc. Jpn.
1980, 53, 3691.
(11) O’Connor, K. J.; Burrows, C. J. J. Org. Chem. 1991, 56,
1344.
(12) (a) Arnold, J. T.; Bayraktaroglu, T. O.; Brown, R. G.;
Heiermann, C. R.; Magnus, W. W.; Ohman, A. B.; Landolt,
R. G. J. Org. Chem. 1992, 57, 391. (b) Bayraktaroglu, T.
O.; Gooding, M. A.; Khatib, S. F.; Lee, H.; Kourouma, M.;
Landolt, R. G. J. Org. Chem. 1993, 58, 1264.
(13) (a) Vol, S.; Vivier, L.; Pérot, G. J. Mol. Catal. A.: Chem.
2001, 172, 241. (b) Imhaoulene, S.; Vivier, L.; Guisnet, M.;
Pérot, G. Tetrahedron 1994, 50, 12913.
(14) Meyer, G.; Rollin, Y.; Perichon, J. Tetrahedron Lett. 1986,
27, 3497.
(15) Bonnichon, F.; Grabner, G.; Guyot, G.; Richard, C. J. Chem.
Soc., Perkin Trans. 2 1999, 1203.
(16) Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124,
14844.
(17) For recent reviews on the area, see: (a) Larhed, M.;
Moberg, C.; Hallberg, A. Acc. Chem. Res. 2002, 35, 717.
(b) Lew, A.; Krutzik, P. O.; Hart, M. E.; Chamberlin, A. R.
J. Comb. Chem. 2002, 4, 95. (c) Lindström, P.; Tierney, J.;
Wathey, B.; Westman, J. Tetrahedron 2001, 57, 9225.
(18) For a review on the concepts, see: Gabriel, C.; Gabriel, S.;
Grant, E. H.; Halstead, B. S.; Mingos, D. M. P. Chem. Soc.
Rev. 1998, 27, 213.
General Procedure (Oil Bath Heating): The reaction protocol
was as in the case of the microwave methodology except that the
tube containing the reagents, after sealing, was placed into a pre-
heated oil bath at 170 ºC. It was held there and stirred for 4 h before
being removed from the oil and allowed to cool. The work-up pro-
cedure was as with the microwave methodology.
(19) Yields for the transformation with other solvents: H2O, 0%,
PEG-400, 8%, DME, 0%.
(20) CAUTION: The DMF is heated above its boiling point so all
necessary precautions should be taken when performing
such experiments. Vessels designed to withhold elevated
pressures must be used. The microwave apparatus used here
incorporates a protective metal cage around the microwave
vessel in case of explosion. After completion of an
experiment, the vessel must be allowed to cool to a
temperature below the boiling point of the solvent before
removal from the microwave cavity and opening to the
atmosphere.
Acknowledgement
The Royal Society is thanked for a University Research Fellowship
(NEL). Funding from King’s College London is acknowledged.
(21) CAUTION: A blast shield should be in place and vessels
designed to withhold elevated pressures must be used. After
completion of an experiment, the vessel must be allowed to
cool before opening to the atmosphere.
Synlett 2003, No. 8, 1145–1148 ISSN 1234-567-89 © Thieme Stuttgart · New York