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G. Chelucci, S. Baldino / Tetrahedron Letters 49 (2008) 2738–2742
Ph
N
Ph
Br
CHO
Br
c
a
b
Br
Br
Br
Br
Me
N
Br
Me
N
Br
Me
N
N
Me
35
34
36
37
Scheme 4. Reagents and conditions: (a) CBr4, PPh3, CH2Cl2, 0 °C to rt, 85%; (b) PhB(OH)2, Pd2dba3 (2.5%), TFP (15%), 1,4-dioxane, Na2CO3
(2.0 equiv), H2O, 65 °C, 14 h, 87%; (c) 18, Pd2dba3 (5%), TFP (30%), 1,4-dioxane, Na2CO3 (2.0 equiv), H2O, 65 °C, 24 h, 51%.
References and notes
1. Chelucci, G.; Addis, D.; Baldino, S. Tetrahedron Lett. 2007, 48, 3359.
2. Minato, A. J. Org. Chem. 1991, 56, 4052.
3. Shen, W.; Wang, L. J. Org. Chem. 1999, 64, 8873.
a
4. Shen, W. Synlett 2000, 737.
Br
Br
5. (a) Some reviews Boronic Acids: Preparation and Applications in
Organic Synthesis and Medicine; Dennis, G. A., Ed.; Wiley-VCH:
Weinheim, 2005; (b) Miyuaura, N.; Suzuki, A. Chem. Rev. 1995, 95,
2457; (c) Suzuki, A. J. Organomet. Chem. 1999, 576, 147; (d) Kotha,
S.; Lahitri, K.; Kashinath, D. Tetrahedron 2002, 58, 9633; (e) Suzuki,
A.; Brown, H. C. In Organic Syntheses via Boranes; Springer:
London, 2003; Vol. 3.
N
N
N
N
38
15
Scheme 5. Reagents and conditions: (a) Cu, DMF, reflux, 2 h, 72%.
1,2-dipyridylethene derivative 15 was submitted to Ull-
mann intramolecular coupling (Scheme 5). Thus, by heat-
ing under reflux a DMF solution of 15 in the presence of
copper powder,1 5-phenylphenanthroline 38 was formed
in 72% yield.
6. Some reviews Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew.
Chem., Int. Ed. 2005, 44, 4442; Li, C.-J. Chem. Rev. 2005, 105, 3095;
Echvarrenm, A. M. Angew. Chem., Int. Ed. 2005, 44, 3962.
7. Bauer, A.; Miller, M. W.; Vice, S. F.; McCombie, S. W. Synlett 2001,
254; Li, Y.-H.; Zhao, X.-M.; Lu, L. J. Fluorine Chem. 2004, 125, 1821.
8. Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 13, 3769.
9. Thanh, D.; Tung, D. T.; Langer, P. Synlett 2006, 2812.
10. New, J. S.; Yevich, J. P.; Temple, D. L., Jr.; New, K. B.; Gross, S. M.;
Schelmmer, R. F.; Eison, M. S.; Taylor, D. P.; Riblet, L. A. J. Med.
Chem. 1988, 31, 618.
11. Illustrative experimental for the tandem one-pot diarylation of 1.1-
dibromo-1-alkenes: 2-bromo-3-(2,2-dibromovinyl)pyridine 10 (0.342 g,
1.0 mmol), phenylboronic acid (128.1 mg, 1.05 equiv), Pd2dba3
(23.0 mg, 0.025 mmol), tri(2-furyl)phosphine (TFP) (35.0 mg, 0.15
mmol) and Cs2CO3 in (1.0 M in H2O, 2.0 mL) in 1,4-dioxane (5.0 mL)
were heated under nitrogen at 65 °C. After 14 h, 2-bromopyridine-
3-boronic acid pinacol ester 18 (298.2 mg, 1.05 mmol), Pd2dba3
(46.0 mg, 0.05 mmol), TFP (70 mg, 0.30 mmol) and Cs2CO3 in (1.0 M
in H2O, 2.0 mL) in 1,4-dioxane (5.0 mL) were added and heating
(65 °C) was continued for 30 h. The reaction mixture was diluted with
ethyl acetate (50 mL), washed with H2O (10 mL) and brine (5 mL).
The organic phase was dried over anhydrous MgSO4, filtered and
concentrated under vacuum. The residue was purified by flash
chromatography (petroleum ether/ethyl acetate = 4/6) to afford
(Z)-2-bromo-3-(2-(2-bromopyridin-3-yl)-2-phenylvinyl)pyridine 15:
270.5 mg (65% yield); oil; 1H NMR (300 MHz, CDCl3): d 8.69 (dd,
1H, J = 4.8, 1.8 Hz), 8.42 (dd, 1H, J = 4.8, 1.8 Hz), 8.17 (ddd, 1H,
J = 7.8, 1.8, 0.9 Hz), 7.73 (dd, 1H, J = 7.8, 1.8 Hz), 7.49–7.40 (m,
3H), 7.39–7.28 (m, 4H), 6.94 (s, 1H). 13C NMR (75.4 MHz, CDCl3): d
155.5, 149.8, 148.6, 141.8, 139.5, 139.4, 137.9, 137.5, 132.3, 129.3,
128.8, 128.4, 127.6, 125.9, 123.0, 122.6.
In conclusion, we have reported the first example of ster-
eoselective tandem arylation–arylation of 1,1-dihalo-1-
alkenes to give trisubstituted alkenes under Suzuki–Miya-
ura cross-coupling reactions. The new protocol has been
exploited to obtain stereodefined 1-aryl(heteroaryl) substi-
tuted cis-1,2-bis(2-bromopyridin-3-yl)ethenes. It is worthy
to note in the sequential cross-coupling processes, the pal-
ladium insertion occurs selectively on the Br–C bond on
the alkene moiety notwithstanding the high electrophilicity
of the Br–pyridine bond. The value of this strategy to
obtain a new entry to 5-aryl-1,10-phenanthrolines has also
been demonstrated. Further studies on this subject are
currently in progress.
Acknowledgements
MIUR (PRIN 2005035123, Regio- and enantioselective
reactions mediated by transition metal catalysts for innova-
tive processes in fine chemicals synthesis) and the Univer-
sity of Sassari are gratefully acknowledged by G.C. for
financial support.