3094
Y. Heo et al. / Tetrahedron Letters 47 (2006) 3091–3094
In summary, we have developed a general and highly
regioselective methodology for the efficient synthesis of
(b) Leadbeater, N. E.; Marco, M. J. Org. Chem. 2003, 68,
8
2
88; (c) Leadbeater, N. E.; Marco, M. Org. Lett. 2002, 4,
973; (d) Blettner, C. G.; K o¨ nig, W. A.; Stenzel, W.;
2
-aryl-6-chlorobenzothiazoles based on Suzuki–Miya-
Schotten, T. J. Org. Chem. 1999, 64, 3885; (e) Wang, H.-J.;
Keilman, J.; Pabba, C.; Chen, Z.-J.; Gregg, B. T.
Tetrahedron Lett. 2005, 46, 2631; (f) N a´ jera, C.; Gil-
Molt o´ , J.; Karlstr o¨ m, S. Adv. Synth. Catal. 2004, 346,
ura reactions of 2,6-dichlorobenzothiazole with aryl-
boronic acids under microwave irradiation. In addition,
the chloride functionality in the 2-aryl-6-chlorobenzo-
thiazoles, produced in this manner, can be used to guide
subsequent metal catalyzed transformations to form
interesting target substances. Continuing studies are
underway in our laboratory to biologically evaluate
the benzothiazole derivatives produced in the current
effort.
1
798.
1
2. For a review of regioselective cross-coupling reactions,
see: Schr o¨ ter, S.; Stock, C.; Bach, T. Tetrahedron 2005, 61,
2245.
13. For an example of regioselective Suzuki–Miyaura cou-
pling, see: Ryu, K.-M.; Gupta, A.; Han, J.-W.; Oh, C. H.;
Cho, C.-G. Synlett 2004, 2197.
1
4. Song, Y. S.; Kim, B. T.; Heo, J.-N. Tetrahedron Lett.
005, 46, 5987.
2
Acknowledgments
1
5. (a) Barder, T. E.; Walker, S. D.; Martinelli, J. R.;
Buchwald, S. L. J. Am. Chem. Soc. 2005, 127, 4685, and
references cited therein; (b) Anderson, K. W.; Buchwald,
S. L. Angew. Chem., Int. Ed. 2005, 44, 6173.
We thank the Ministry of Commerce, Industry, and
Energy for the financial support (TS051-04 and TS051-
0
2) of this work.
16. General procedure for Suzuki–Miyaura reaction. Reac-
TM
tions were conducted by using a Biotage Initiator EXP
microwave reactor. To a thick-well borosilicate glass vial
(
5 mL) was added 2,6-dichlorobenzothiazole 3 (1 mmol),
References and notes
Pd(PPh ) (4 mol %), arylboronic acid 4 (1.2 mmol), and
3
4
Na
2
CO
3
(2.4 mmol) sequentially. The mixture was dis-
O (4 mL/1 mL) and degassed with
1
. (a) Mathis, C. A.; Wang, Y.; Holt, D. P.; Huang, G.-F.;
Debnath, M. L.; Klunk, W. E. J. Med. Chem. 2003, 46,
740; (b) Alagille, D.; Baldwin, R. M.; Tamagnan, G. D.
solved in dioxane/H
2
argon over a 5 min period. Then, the reaction vial was
sealed and placed in the microwave reactor and irradiated
at 150 °C for 5 min. After being cooled to rt, the mixture
2
Tetrahedron Lett. 2005, 46, 1349.
2
. Hutchinson, I.; Chua, M.-S.; Browne, H. L.; Trapani, V.;
Bradshaw, T. D.; Westwell, A. D.; Stevens, M. F. G. J.
Med. Chem. 2001, 44, 1446.
. Stevens, M. F. G.; Wells, G.; Westwells, A. D.; Poole, T.
D. PCT Int. Appl., WO 0304479, 2003.
4
was diluted with EtOAc, dried over MgSO , and filtered
through a short Celite pad. The solution was concentrated
in vacuo and the residue was subjected to silica gel flash
column chromatography (EtOAc/hexanes) to yield the
product. Adduct 6b, mp 138–140 °C. H NMR (300 MHz,
CDCl ) d 8.02 (dd, 2H, J = 6.8, 2.1 Hz), 7.92 (d, 1H,
3
1
4
. Yamamoto, K.; Fujita, M.; Tabashi, K.; Kawashima, Y.;
Kato, E.; Oya, M.; Iso, T.; Iwao, J. J. Med. Chem. 1983,
3
J = 8.7 Hz), 7.85 (d, 1H, J = 2.1 Hz), 7.42 (dd, 1H,
J = 8.7, 2.1 Hz), 7.00 (dd, 2H, J = 6.8, 2.1 Hz), 3.89 (s,
31, 919.
5
. Gao, R.; Ho, D. G.; Hernandez, B.; Selke, M.; Murphy,
D.; Djurovich, P. I.; Thompson, M. E. J. Am. Chem. Soc.
1
3
3
H); C NMR (125 MHz, CDCl
3
) d 168.5, 162.3, 153.0,
1
36.2, 130.8, 129.3, 127.2, 126.2, 123.7, 121.3, 114.6, 55.7;
2002, 124, 14828.
+
MS (EI) m/z M for C14
H
10ClNOS calcd 275.02, found
77 (34), 275 (M , 100), 260 (28), 232 (16), 197 (16), 188
5), 149 (5).
7. Appukkuttan, P.; Eycken, E. V.; Dehaen, W. Synlett 2003,
8, 1204.
8. (a) Heo, J.-N.; Song, Y. S.; Kim, B. T. Tetrahedron Lett.
005, 46, 4621; (b) Charles, M. D.; Schultz, P.; Buchwald,
6
. (a) Shi, D.-F.; Bradshaw, T. D.; Wrigley, S.; McCall, C. J.;
Lelieveld, P.; Fichtner, I.; Stevens, M. F. G. J. Med.
Chem. 1996, 39, 3375; (b) Hein, D. W.; Alheim, R. J.;
Leavitt, J. J. J. Am. Chem. Soc. 1957, 79, 427; (c) Ben-
Alloum, A.; Bakkas, S.; Soufiaoui, M. Tetrahedron Lett.
+
2
(
1
1
1
1997, 38, 6395; (d) Chakraborti, A. K.; Selvam, C.; Kaur,
2
G.; Bhagat, S. Synlett 2004, 851.
S. L. Org. Lett. 2005, 7, 3965; Procedure for palladium-
catalyzed amination: To a thick-well borosilicate glass vial
7
8
. (a) Paul, S.; Gupta, M.; Gupta, R. Synth. Commun. 2002,
32, 3541; (b) Roe, A.; Tucker, W. P. J. Heterocycl. Chem.
1965, 2, 148; (c) Stanetty, P.; Krumpak, B. J. Org. Chem.
1996, 61, 5130; (d) Ares, J. J. Synth. Commun. 1991, 21,
625.
(
5 mL) was added benzothiazole 6b (149 mg, 0.54 mmol),
Pd (dba) (3 mg, 1 mol % of Pd), 5 (3 mg, 1.5 mol %),
2
3
morpholine (56 lL, 0.65 mmol), and NaOt-Bu (73 mg,
.76 mmol) sequentially. The mixture was dissolved in
0
. For reviews, see: (a) Bellina, F.; Carpita, A.; Rossi, R.
Synthesis 2004, 2419; (b) Hassan, J.; S e´ vignon, M.; Gozzi,
C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359;
toluene (3 mL) and degassed with argon over 5 min. Then,
the reaction vial was sealed and placed in the microwave
reactor and irradiated at 150 °C for 10 min. After cooled
to rt, the mixture was diluted with EtOAc and filtered
through a short Celite pad. The solution was concentrated
in vacuo and the residue was purified by silica gel flash
(
c) Kotha, S.; Lahiri, K.; Kashinath, D. Tetrahedron 2002,
58, 9633; (d) Suzuki, A. J. Organomet. Chem. 1999, 576,
147; (e) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95,
2457.
column chromatography (40% EtOAc/hexanes) to provide
9
. Majo, V. J.; Prabhakaran, J.; Mann, J. J.; Kumar, J. S. D.
1
8
(136 mg, 77%): mp 180–182 °C; H NMR (300 MHz,
Tetrahedron Lett. 2003, 44, 8535.
DMSO-d ) d 7.95 (d, 2H, J = 8.8 Hz), 7.84 (d, 1H,
1
0. For recent reviews on microwave heating technology, see:
6
J = 9.0 Hz), 7.56 (d, 1H, J = 2.3 Hz), 7.21 (dd, 1H,
J = 9.0, 2.4 Hz), 7.09 (d, 2H, J = 8.8 Hz), 3.84 (s, 3H),
(
(
a) Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250;
b) Loupy, A. Microwaves in Organic Synthesis; Wiley-
1
3
3
.77 (t, 4H, J = 4.7 Hz), 3.20 (t, 4H, J = 4.7 Hz);
C
VCH: Weinheim, 2002; (c) Lidstr o¨ m, P.; Tierney, J.;
Wathey, B.; Westman, J. Tetrahedron 2001, 57, 9225.
1. For representative examples of the Suzuki–Miyaura reac-
tions using microwave irradiation, see: (a) Miao, G.; Ye,
P.; Yu, L.; Baldino, C. M. J. Org. Chem. 2005, 70, 2332;
NMR (75.5 MHz, DMSO-d ) d 163.4, 161.2, 149.1, 147.2,
6
1
4
3
35.9, 128.3, 125.9, 122.5, 116.0, 114.7, 106.5, 66.1, 55.4,
+
1
18 2 2 2
8.9; LC/MS (ESI) m/z M for C18H N O S calcd
26.11, found 326.72.