2972
D. Alberico, M. Lautens
LETTER
General Procedure for the Alkylation–Alkenylation Reaction
3-(2,3,5,6-Tetrahydrobenzo[1,2-b;5,4-b¢]difuran-4-yl)acrylic
Acid tert-Butyl Ester (2)
Microwave-assisted reactions were preformed in a Emrys Liberator
model from Biotage (formerly Personal Chemistry) using Biotage
Microwave Vials (2–5 mL). Microwave irradiation time was con-
ducted using ramp time and hold time at the final temperature.
(3) (a) Catellani, M.; Frignani, F.; Rangoni, A. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 119. (b) Catellani, M.; Mealli, C.;
Motti, E.; Paoli, P.; Perez-Carreño, E.; Pregosin, P. S. J. Am.
Chem. Soc. 2002, 124, 4336. (c) Catellani, M. Synlett 2003,
298. (d) Catellani, M. Top. Organomet. Chem. 2005, 14, 21.
(4) (a) Lautens, M.; Piguel, S. Angew. Chem. Int. Ed. 2000, 39,
1045. (b) Lautens, M.; Paquin, J.-F.; Piguel, S.; Dahlmann,
M. J. Org. Chem. 2001, 66, 8127. (c) Lautens, M.; Paquin,
J.-F.; Piguel, S. J. Org. Chem. 2002, 67, 3972. (d)Alberico,
D.; Paquin, J.-F.; Lautens, M. Tetrahedron 2005, 61, 6283.
(e) Bressy, C.; Alberico, D.; Lautens, M. J. Am. Chem. Soc.
2005, 127, 13148.
(5) Pache, S.; Lautens, M. Org. Lett. 2003, 5, 4827.
(6) Monte, A. P.; Waldman, S. R.; Marona-Lewicka, D.;
Wainscott, D. B.; Nelson, D. L.; Sanders-Bush, E.; Nichols,
D. E. J. Med. Chem. 1997, 40, 2997.
(7) (a) Huang, K.-S.; Lin, M.; Yu, L.-N.; Kong, M. Tetrahedron
2000, 56, 1321. (b) Chambers, J. J.; Kurrasch-Orbaugh, D.
M.; Nichols, D. E. Bioorg. Med. Chem. Lett. 2002, 12, 1997.
(8) (a) Lindstrom, P.; Tierney, J.; Wathey, B.; Westman, J.
Tetrahedron 2001, 57, 9225. (b) Larhed, M.; Moberg, C.;
Hallberg, A. Acc. Chem. Res. 2002, 35, 717.
To a microwave reaction vessel were added Cs2CO3 (323 mg, 1.00
mmol, 5 equiv), norbornene (56.0 mg, 0.600 mmol, 3 equiv),
Pd(OAc)2 (4.50 mg, 0.0200 mmol, 10 mol%), PPh3 (11.5 mg,
0.0440 mmol, 22 mol%), aryl iodide 1 (90.0 mg, 0.200 mmol, 1
equiv) and tert-butyl acrylate (146 mL, 1.00 mmol, 5 equiv). The
vessel was sealed and flushed with N2. Through the septa was added
degassed dry DME (4 mL). The reaction vessel was subjected to mi-
crowave irradiation at 190 °C for 5 min. The mixture was diluted
with Et2O (4 mL) and quenched with H2O (4 mL). The aqueous lay-
er was extracted with Et2O (3×) and the combined organic layers
were washed with brine, dried with anhyd MgSO4 and filtered.
Removal of the solvent and purification by flash chromatography
using 10% EtOAc–hexanes as eluant resulted in 2 (49.1 mg, 85%)
as a pale yellow solid; mp 108–109 °C. Rf = 0.35 (silica gel, 10%
EtOAc–hexanes). IR (neat). n = 1707, 1593, 1440, 1293, 1154 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.66 (d, J = 16.3 Hz, 1 H), 6.32 (s,
1 H), 6.17 (d, J = 16.4 Hz, 1 H), 4.61 (t, J = 8.6 Hz, 4 H), 3.25 (t,
J = 8.6 Hz, 4 H), 1.53 (s, 9 H). 13C NMR (75 MHz, CDCl3): d =
166.6, 160.9, 140.4, 127.3, 123.2, 118.4, 94.3, 81.0, 72.2, 29.6,
28.4. HRMS: m/z calcd for C17H20O4 [M]+: 288.1363; found:
288.1361.
(9) Willans, C. E.; Mulders, J. M. C. A.; de Vries, J. G.; de
Vries, A. H. M. J. Organomet. Chem. 2003, 687, 494; and
references cited therein.
(10) (a) Ahrendt, K. A.; Bergman, R. G.; Ellman, J. A. Org. Lett.
2003, 5, 1301. (b) Thalji, R. K.; Ahrendt, K. A.; Bergman,
R. G.; Ellman, J. A. J. Org. Chem. 2005, 70, 6775.
(11) Kapadia, G. J.; Fayez, M. B. E. J. Pharm. Sci. 1970, 59,
1699.
(12) (a) Nichols, D. E.; Glennon, R. A. In Hallucinogens:
Neurochemical, Behavioral, and Clinical Perspectives;
Jacobs, B. L., Ed.; Raven Press: New York, 1984, 95–142.
(b) Nichols, D. E. In Amphetamine and Its Analogues; Cho,
A. K.; Segal, D. S., Eds.; Academic Press: San Diego CA,
1994, 3–41. (c) Nichols, D. E. Pharmacol. Ther. 2004, 101,
131.
Acknowledgment
We gratefully acknowledge the financial support of the Natural
Sciences and Engineering Research Council (NSERC) of Canada,
the Merck Frosst Centre for Therapeutic Research for an Industrial
Research Chair, and the University of Toronto.
(13) (a) Glennon, R. A.; Titeler, M.; McKenney, J. D. Life Sci.
1984, 35, 2502. (b) Rasmussen, K.; Aghajanian, G. K.
Brain Res. 1986, 385, 395. (c) Titeler, M.; Lyon, R. A.;
Glennon, R. A. Psychopharmacology 1988, 94, 213.
(d) Appel, J. B.; Callahan, P. M. Eur. J. Pharmacol.
1989, 159, 41. (e) Aghajanian, G. K.; Marek, G. J.
Neuropsychopharmacology 1999, 21, 16S. (f) Aghajanian,
G. K.; Marek, G. J. Brain Res. Rev. 2000, 31, 302.
(14) Green, K. J. Org. Chem. 1991, 56, 4325.
References and Notes
(1) (a) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. Engl.
1993, 32, 131. (b) Tietze, L. F. Chem. Rev. 1996, 96, 115.
(c) Denmark, S. E.; Thorarensen, A. Chem. Rev. 1996, 96,
137. (d) Tietze, L. F.; Rackelmann, N. Pure Appl. Chem.
2004, 76, 1967.
(2) (a) Grigg, R.; Sridharan, V. J. Organomet. Chem. 1999, 576,
65. (b) de Meijere, A.; Bräse, S. J. Organomet. Chem. 1999,
576, 88. (c) Larock, R. C. J. Organomet. Chem. 1999, 576,
111. (d) Yet, L. Chem. Rev. 2000, 100, 2963. (e) Poli, G.;
Giambastini, G.; Heumann, A. Tetrahedron 2000, 56, 5959.
(f) Cacchi, S.; Fabrizi, G.; Goggiomani, A. Heterocycles
2002, 56, 613. (g) Cacchi, S.; Fabrizi, G.; Parisi, L. M.
Heterocycles 2002, 58, 667. (h) Battistuzzi, G.; Cacchi, S.;
Fabrizi, G. Eur. J. Org. Chem. 2002, 2671.
(15) Gómez-Sánchez, E.; Marco-Contelles, J. Tetrahedron 2005,
61, 1207.
Synlett 2006, No. 18, 2969–2972 © Thieme Stuttgart · New York