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L. Öhberg, J. Westman
LETTER
Figure 4 Reaction conditions: i Pd(PPh3)2Cl2, EtOH, Et3N, 140 °C, 6 min. ii Et3N, DCE, 140 °C, 5 min. iii NaBH(OAc)3, DCE, 170 °C, 9
min. iv Et3N, DCE, 170 °C, 5 min.
Storer, R. I.; Taylor, S. J. J. Chem. Soc., Perkin Trans. 1
2000, 3815.
column of silica gel and eluted with EtOAc and heptane
(1:3)to give the product in good yield.
(4) Gedye, R.; Smith, F.; Westaway, K.; Ali, H.; Baldisera, L.;
Laberge, L.; Rousell, J. Tetrahedron Lett. 1986, 27, 279.
(5) Lidström, P.; Thierney, J.; Whatey, B.; Westman, J.
Tetrahedron 2001, 57, 9225.
(6) (a) Cotterill, I. C.; Usyatinsky, A. Y.; Arnold, J. M.; Clark,
D. S.; Dordick, J. S.; Michels, P. C.; Khmelnitsky, Y. L.
Tetrahedron Lett. 1998, 39, 1117. (b) Hoel, A. M. L.;
Nielsen, J. Tetrahedron Lett. 1999, 40, 3941.
(7) Gong, Y.-D.; Kurth, M. J. Tetrahedron Lett. 1998, 39, 3379.
(8) Sim, M. M.; Ganesan, A. J. Org. Chem. 1997, 62, 3230.
(9) Matthews, J.; Rivero, R. A. J. Org. Chem. 1997, 62, 6090.
(10) A SmithsynthesizerTM available from Personal Chemistry
AB, Uppsala, Sweden was used in this project. The
instrument is run under tempereature control and the
temperature is recorded through an IR-sensor.
(11) (a) Larhed, M.; Hoshino, M.; Hadida, S.; Curran, D. P.;
Hallberg, A. J. Org. Chem. 1997, 62, 5583. (b) Larhed, M.;
Lindeberg, G.; Hallberg, A. Tetrahedron Lett. 1996, 37,
8219. (c) Bletttner, C. G.; König, W. A.; Stenzel, W.;
Schotten, T. J. Org. Chem. 1999, 64, 3885. (d) Kabalka, G.
W.; Pagni, R. M.; Wang, L.; Namboodiri, V.; Hair, C. M.
Green Chem. 2000, 2, 120.
(16) General experimental procedure for the library protocol:
A boronic acid (0.6 mmol), p-bromobenzaldehyde (0.66
mmol), (PPh3)2PdCl2 (0.012 mmol) and Et3N (1.2 mmol)
were dissolved in ethanol (2.5 mL) in a process vial, which
was sealed with a teflon septum and then placed in the
microwave cavity. The reaction mixture was stirred for 5
min at 140 °C, the residue was filtered through a silica plug
and evaporated to dryness. The crude was then dissolved in
DCE (2.5 mL), 4 aliquots of 0.5 mL each (0.125 mmol) were
placed in 4 new glass vials. An amino acid ester (0.25
mmol), Et3N (0.137 mmol) and DCE (2.0 mL) were added to
each vial, which was then sealed and placed in the
microwave cavity. The reaction mixture was stirred for 7
min at 140 °C, NaBH(OAc)3 (0.175 mmol) was then added
to the reaction mixture, the glass vial was resealed and
heated for an additional 9 min at 170 °C. An isothiocyanate
(0.25 mmol) and Et3N (0.25 mmol) were then added to each
reaction vial and the reaction mixture was heated for 5 min
at 170 °C, thereafter evaporated to dryness. For the synthesis
of 1-[4-(1-benzofuran-2-yl)benzyl]-5-benzyl-3-(4-fluoro-
phenyl)-2-thioxo-4-imidazolidinone (DGHM), benzofuran-
2-boronic acid, L-phenyalanine ethyl ester hydrochloride
and p-fluorophenyl isothiocyanate were used. Silica gel
purification (heptane–EtOAc 5:1- 4:1)gave the product in
55% yield. 1H NMR (300 MHz, CDCl3): 3.2–3.6 (CH2,
Phe, J = 4.18, dd, 2 H), 4.3 (CH, Phe, J = 4.18, tr, 1 H), 4.5
(CH2–N, J = 15.1, d, 1 H), 6.0 (CH2–N, J = 15.1, d, 1 H),
6.9–7.9 (aromatic H, 18 H), 13C NMR (300 MHz, CDCl3):
34.4 (CH2, Phe), 48.8 (CH2-N), 62.3 (CH, Phe), 116.3-141.9
(aromatic C, 26C), 172.3 (C=S), 183.2 (C=O).
(12) Stanforth, S. P. Tetrahedron 1998, 54, 263.
(13) Weichert, A.; Bauer, M.; Wirsig, P. Synlett 1996, 473.
(14) Palmgren, A.; Thorarensen, A.; Bäckvall, J. E. J. Org. Chem.
1998, 63, 3764.
(15) Purification procedure for the Negishi reaction: SiO2 was
added to the reaction mixture. The solvent was evaporated
and the silica supported residue was then poured on a short
Synlett 2001, No. 12, 1893–1896 ISSN 0936-5214 © Thieme Stuttgart · New York