Job/Unit: O50328
/KAP1
Date: 24-04-15 12:12:20
Pages: 8
A. H. Sandtorv, K. W. Törnroos, H.-R. Bjørsvik
FULL PAPER
General Method for the bis-Stille Coupling Reaction on the
Imidazole Backbone: N-DMAS-4,5-Diiodoimidazole (0.050 g,
J. Schwartz, W. H. Schunack, H. Stark, Bioorg. Med. Chem.
003, 11, 2163–2174.
2
[
3] a) S. Khabnadideh, Z. Rezaei, A. Khalafi-Nezhad, R. Bahrina-
jafi, R. Mohamadi, A. A. Farrokhroz, Bioorg. Med. Chem.
Lett. 2003, 13, 2863–2865; b) K. Bhandari, N. Srinivas, G. B. S.
Keshava, P. J. Shukla, Eur. J. Med. Chem. 2009, 44, 437–447.
4] A. K. Saha, L. Liu, R. L. Simoneaux, M. J. Kukla, P. v. Mar-
ichal, F. Odds, Bioorg. Med. Chem. Lett. 2000, 10, 2175–2178.
5] a) A. S. Clark, B. Deans, M. F. G. Stevens, M. J. Tisdale, R. T.
Wheelhouse, B. J. Denny, J. A. Hartley, J. Med. Chem. 1996,
38, 1493–1504; b) M. J. Wanner, G. J. Koom, J. Chem. Soc.
Perkin Trans. 1 2002, 1877–1880.
3 4
0.11 mmol), Pd(PPh ) (5%) and CuI (1 equiv.) were transferred to
a microwave reactor tube furnished with a magnetic stirring bar.
The tube was sealed and carefully flushed with argon through the
septa. A separate tube was sealed and flushed with argon, before
DMF (5 mL) and the Sn reagent (3 equiv.) were added by means
of syringes. The reactor tube containing both solvent and tin rea-
gent was degassed with ultrasound for at least 1 min. Finally, the
solvent/Sn reagent mixture was added to the tube containing imid-
azole and catalyst, stirred until all the solids were dissolved and
placed in the microwave cavity and heated at 110 °C for 2 h. The
post-reaction mixture was diluted in diethyl ether (20 mL) and
shaken with NaF (1 m, 3ϫ 10 mL). The organic phase was then
[
[
[6] N. Li, H. Zhu, T.-W. Chu, Z. Yang, Eur. J. Med. Chem. 2013,
69, 223–231.
[
7] H.-R. Bjørsvik, A. H. Sandtorv, Studies in Natural Products
Chemistry, chapter 2: Synthesis of Imidazole Alkaloids Origi-
nated in Marine Sponges (Ed.: Atta-ur-Rahman), Elsevier, Am-
sterdam, 2014, 42, p. 33–57.
2 4
washed with brine (10 mL), and dried with anhydrous Na SO . The
drying agent was filtered, and the solvent evaporated under reduced
pressure. The products could in most cases be purified with flash
chromatography with hexanes:EtOAc (1:1).
[
8] Y. Chen, H. V. R. Dias, C. J. Lovely, Tetrahedron Lett. 2003,
1379–1382.
[
[
9] C. J. Lovely, H. Du, H. V. R. Dias, Heterocycles 2003, 70, 1–7.
10] A. H. Sandtorv, H.-R. Bjørsvik, Adv. Synth. Catal. 2013, 355,
499–507.
N-DMAS-4,5-Divinylimidazole (10a): The title compound was iso-
lated as a colorless oil in 60% yield. R
f
= 0.55 [hexanes:EtOAc
): δ = 7.88 (s, 1 H), 6.85 (m, 1 H), 6.70 (m,
H), 6.09 (d, 1 H), 5.57 (m, 2 H), 5.33 (m, 1 H), 2.84 (s, 6 H) ppm.
1
(1:1)]. H NMR (CDCl
3
[11] A. H. Sandtorv, H.-R. Bjørsvik, Adv. Synth. Catal. 2013, 355,
1
1
3
3231–3243.
C NMR (CDCl
24.8, 116.4, 38.4 ppm. HRMS (DART+): m/z [MH] calcd. for
: 228.08067; 228.08008 found.
3
): δ = 139.5, 138.3, 138.2, 126.9, 126.8, 124.2,
+
[12] J. K. Stille, Angew. Chem. Int. Ed. Engl. 1986, 25, 508–524; An-
gew. Chem. 1986, 98, 504.
[
1
9 14 3 2 2
C H N O S
13] a) For a recent review, see: M. M. Heravi, E. Hashemi, F. Az-
imian, Tetrahedron 2014, 70, 7–21; b) C. Souris, F. Frèbault,
A. Patel, D. Audisio, K. N. Houk, N. Maulide, Org. Lett. 2013,
13, 3242–3245; c) D. Amans, L. Bareille, V. Bellosta, J. Cossy,
J. Org. Chem. 2009, 74, 7665–7674; d) W. P. Unsworth, K. A.
Gallagher, M. Jean, J. P. Schmidt, L. J. Diorazio, R. J. K. Tay-
lor, Org. Lett. 2013, 15, 262–265; e) M. D. Shair, T. Y. Yoon,
K. K. Mosny, T. C. Chou, S. J. Danishefsky, J. Am. Chem. Soc.
N-DMAS-4,5-Bis(2Ј-furanyl)imidazole (10b): The title compound
was isolated as a tan oil in 71% yield. R = 0.43 [hexanes:EtOAc
): δ = 8.09 (s, 1 H), 7.62 (m, 1 H), 7.38 (s,
f
1
(
1:1)]. H NMR (CDCl
3
1
2
1
H), 6.75 (m, 1 H), 6.59 (m, 1 H), 6.38 (m, 1 H), 6.34 (m, 1 H),
.67 (s, 6 H) ppm. 13C NMR (CDCl
): δ = 147.4, 144.2, 143.8,
[31]
3
40.2, 140.0, 137.1, 115.6, 115.3, 11.9, 11.4, 108.3, 37.6 ppm.
+
HRMS (DART+): m/z [MH] calcd. for C13
08.07121 found.
14 3 3
H N O S: 308.07050;
1
996, 118, 9509–9525; f) K. C. Nicolaou, T. K. Chakraborty,
A. D. Piscopio, N. Minowa, P. Bertinato, J. Am. Chem. Soc.
993, 115, 4419–4420; g) K. C. Nicolaou, A. D. Piscopio, P.
3
1
N-DMAS-4,5-Bis(2Ј-thiophenyl)imidazole (10c): The title com-
pound was isolated as colorless crystals in a yield of 73%. R
Bertinato, T. K. Chakraborty, N. Minowa, K. Koide, Chem.
Eur. J. 1995, 1, 318–333.
f
=
1
0
7
6
1
1
.65 [hexanes:EtOAc (1:1)]. H NMR (CDCl
3
): δ = 8.10 (s, 1 H),
[14] P. Espinet, A. M. Echavarren, Angew. Chem. Int. Ed. 2004, 43,
.61 (m, 1 H), 7.32 (m, 1 H), 7.21 (m, 2 H), 6.94 (m, 2 H), 2.61 (s,
4704–4734; Angew. Chem. 2004, 116, 4808.
H) ppm. 13C NMR (CDCl
[31]
δ = 139.9, 139.6, 139.2, 135.8, [15] K. Pchalek, M. P. Hay, J. Org. Chem. 2006, 71, 6530–6535.
3
):
30.1, 129.7, 128.3, 127.9, 127.5, 126.1, 125.7, 125.2, 125.0, 124.7,
[16] For some recent reviews see for example: a) S. Schröter, C.
Stock, T. Bach, Tetrahedron 2005, 9, 2245–2267; b) M.
Schnürch, R. Flasik, A. F. Khan, M. Spina, M. M. Mihovi-
lovic, P. Stanetty, Eur. J. Org. Chem. 2006, 15, 3238–3307.
16.6, 37.3, 37.2, 37.1 ppm. HRMS (DART+): m/z [MH]+ calcd.
14 3 2 3
for C13H N O S : 340.02481; 340.02315 found.
CCDC-1052400 contains the supplementary crystallographic data
for this paper (compound 10c). These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[
17] a) M. D. Cliff, S. G. Pyne, J. Org. Chem. 1995, 60, 2378–2383;
b) M. D. Cliff, S. G. Pyne, Tetrahedron 1996, 52, 13703–13712;
c) C. J. Lovely, H. Du, H. V. R. Dias, Org. Lett. 2001, 3, 1319–
1322; d) C. J. Lovely, H. Du, R. Sivappa, M. R. Bhandari, Y.
He, H. V. R. Dias, J. Org. Chem. 2007, 72, 3741–3749; e) Y.
Morita, Y. Yakiyama, T. Murata, K. Nakasuji, Solid State Sci.
2008, 10, 1720–1723.
Acknowledgments
[
18] a) M. R. Bhandari, R. Sivappa, C. J. Lovely, Org. Lett. 2009,
1
1, 1535–1538; b) R. Selig, D. Schollmeyer, W. Albrecht, S.
A. H. S. gratefully acknowledges the Department of Chemistry at
the University of Bergen for funding his research fellowship. The
authors acknowledge Mr. Serhii Tretiakov for excellent technical
assistance in preparing the starting material 3 and 8.
Laufer, Tetrahedron 2011, 67, 9204–9213.
[
[
[
19] M. Mizutani, F. Inagaki, T. Nakanishi, C. Yanagihara, I. Ta-
mai, C. Mukai, Org. Lett. 2011, 13, 1796–1799.
20] W. J. Scott, J. K. Stille, J. Am. Chem. Soc. 1986, 108, 3033–
3040.
21] a) L. S. Liebeskind, R. W. Fengl, J. Org. Chem. 1990, 55, 5359–
[
1] B. Narasimhan, D. Sharma, P. Kumar, Med. Chem. Res. 2011,
0, 1119–1140.
5
6
364; b) Y. Peng, W.-D. Z. Li, Eur. J. Org. Chem. 2010, 6703–
718.
2
[
2] See, for example: a) R. C. Young, G. J. Durant, J. C. Emmett,
C. R. Ganellin, M. J. Graham, R. C. Mitchell, H. D. Prain,
M. L. Roantree, J. Med. Chem. 1986, 29, 44–49; b) R. C. Vol-
linga, W. M. P. B. Menge, R. Leurs, H. Timmerman, J. Med.
[
22] S. P. H. Mee, V. Lee, J. E. Baldwin, Angew. Chem. Int. Ed. 2004,
3, 1132–1132; Angew. Chem. 2004, 116, 1152.
[23] A. L. Casado, P. Espinet, Organometallics 2003, 22, 1305–1309.
4
Chem. 1995, 38, 2244–2250; c) S. Grabmann, J. Apelt, W. Sippl, [24] V. Farina, S. Kapadia, B. Krishnan, C. Want, L. S. Liebeskind,
X. Ligneau, H. H. Pertz, Y. H. Zhao, J. Arrang, C. R. Ganellin, J. Org. Chem. 1994, 59, 5905–5911.
6
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