LETTER
Preparation of Aryl Sulfides
2893
Table 3 Cross-Coupling of Aryl Bromide with Thiolsa (continued)
Acknowledgment
We gratefully acknowledge financial support for this research by a
Grant-in-Aid for Scientific Research from MEXT. We also thank
the Center for Instrumental Analysis KIT for the measurement of
analytical data.
Entry Aryl Bromide
Thiol
Yield (%)b
27
C8H17SH
99
Br
S
Br
28
C8H17SH
C8H17SH
95
99
References and Notes
(1) Metzner, P.; Thuillier, A. Sulfur Reagents in Organic
Synthesis; Katritzky, A. R.; Meth-Cohn, O.; Rees, C. W.,
Eds.; Academic Press: London, 1994.
S
Br
29
(2) (a) De Martino, G.; Edler, M. C.; La Regina, G.; Coluccia,
A.; Barbera, M. C.; Barrow, D.; Nicholson, R. I.; Chiosis,
G.; Brancale, A.; Hamel, E.; Artico, M.; Silvestri, R. J. Med.
Chem. 2006, 49, 947. (b) Alcaraz, M. L.; Atkinson, S.;
Cornwall, P.; Foster, A. C.; Gill, D. M.; Humphries, L. A.;
Keegan, P. S.; Kemp, R.; Merifield, E.; Nixon, R. A.; Noble,
A. J.; O’Beirne, D.; Patel, Z. M.; Perkins, J.; Rowan, P.;
Sadler, P.; Singleton, J. T.; Tornos, J.; Watts, A. J.;
Woodland, I. A. Org. Process Res. Dev. 2005, 9, 555.
(c) Liu, L. P.; Stelmach, J. E.; Natarajan, S. R.; Chen, M. H.;
Singh, S. B.; Schwartz, C. D.; Fitzgerald, C. E.; O’Keefe,
S. J.; Zaller, D. M.; Schmatz, D. M.; Doherty, J. B. Bioorg.
Med. Chem. Lett. 2003, 13, 3979.
N
a Unless otherwise stated, reaction conditions: thiol (1.0 equiv),
[Pd2(dba)3] (1 mol%), DPPF (2 mol%), DIPEA (1.1 equiv), reflux,
3 h, under N2.
b Isolated yield.
c [Pd2(dba)3] (2 mol%), DPPF (4 mol%), DIPEA (1.1 equiv) were
used.
d Heated at reflux for 6 h.
e [Pd2(dba)3] (2 mol%), DPPF (4 mol%), DIPEA (2.4 equiv) were
used.
f Heated at reflux for 15 h.
g DIPEA (2.4 equiv) was used.
(3) Kondo, T.; Mitsudo, T. Chem. Rev. 2000, 100, 3205.
(4) (a) Migita, T.; Shimizu, T.; Asami, Y.; Shiobara, J.; Kato,
Y.; Kosugi, M. Bull. Chem. Soc. Jpn. 1980, 53, 1385.
(b) Kosugi, M.; Shimizu, T.; Migita, T. Chem. Lett. 1978,
13.
(5) (a) Eichman, C. C.; Stambuli, J. P. J. Org. Chem. 2009, 74,
4005. (b) Dahl, T.; Tornoe, C. W.; Bang-Andersen, B.;
Nielsen, P.; Jorgensen, M. Angew. Chem. Int. Ed. 2008, 47,
1726. (c) Norris, T.; Leeman, K. Org. Process Res. Dev.
2008, 12, 869. (d) Lee, J. Y.; Lee, P. H. J. Org. Chem. 2008,
73, 7413. (e) Mispelaere-Canivet, C.; Spindler, J. F.; Perrio,
S.; Beslin, P. Tetrahedron 2005, 61, 5253. (f) Itoh, T.;
Mase, T. Org. Lett. 2004, 6, 4587.
(6) (a) Jammi, S.; Barua, P.; Rout, L.; Saha, P.; Punnlyamurthy,
T. Tetrahedron Lett. 2008, 49, 1484. (b) Cao, Y.-Q.; Zhang,
Z.; Guo, Y.-X.; Wu, G.-Q. Synth. Commun. 2008, 38, 1325.
(c) Zhang, Y. G.; Ngeow, K. C.; Ying, J. Y. Org. Lett. 2007,
9, 3495. (d) Millois, C.; Diaz, P. Org. Lett. 2000, 2, 1705.
(7) (a) Bagley, M. C.; Dix, M. C.; Fusillo, V. Tetrahedron Lett.
2009, 50, 3661. (b) Haldón, E.; Álvarez, E.; Nicasio, M. C.;
Pérez, P. J. Organometallics 2009, 28, 3815. (c) Herrero,
M. T.; SanMartin, R.; Domínguez, E. Tetrahedron 2009, 65,
1500. (d) Jammi, S.; Sakthivel, S.; Rout, L.; Mukherjee, T.;
Mandal, S.; Mitra, R.; Saha, P.; Punniyamurthy, T. J. Org.
Chem. 2009, 74, 1971. (e) Larsson, P. F.; Correa, A.; Carril,
M.; Norrby, P. O.; Bolm, C. Angew. Chem. Int. Ed. 2009, 48,
5691. (f) Prasad, D. J. C.; Naidu, A. B.; Sekar, G.
Tetrahedron Lett. 2009, 50, 1411. (g) Rout, L.; Saha, P.;
Jammi, S.; Punniyamurthy, T. Eur. J. Org. Chem. 2008,
640. (h) She, J.; Jiang, Z.; Wang, Y. G. Tetrahedron Lett.
2009, 50, 593. (i) Xu, H. J.; Zhao, X. Y.; Deng, J.; Fu, Y.;
Feng, Y. S. Tetrahedron Lett. 2009, 50, 434. (j) Xu, H. J.;
Zhao, X. Y.; Fu, Y.; Feng, Y. S. Synlett 2008, 3063.
(k) Goyot, O.; Gingras, M. Tetrahedron Lett. 2009, 50,
1977. (l) Prasad, D. J. C.; Seker, G. Synthesis 2010, 79.
(8) Wong, Y.-C.; Jayanth, T. T.; Cheng, C.-H. Org. Lett. 2006,
8, 5613.
To study the scope of this procedure, the cross-coupling of
various aryl bromides with alkyl and aromatic thiols was
then studied (Table 3). In general, aryl bromides bearing
either an electron-donating group or an electron-with-
drawing group were successfully coupled with aromatic
and alkyl thiols in good yields. This coupling is tolerant of
a wide range of functional groups, including hydroxy,
amino, cyano, nitro, formyl, and carboxyl groups. The
coupling of aromatic thiols with aryl bromides bearing an
electron-donating group required high catalyst loading
(entries 3, 6, 11, and 12). Sterically demanding ortho-sub-
stituted aryl bromides reacted with secondary and tertiary
thiols in the presence of the same catalyst loading, al-
though longer reaction times were required (entries 5 and
10). The coupling of a more hindered di-ortho-substituted
aryl bromide did not occur (entry 7). Aryl bromides with
para-hydroxy or para-amino groups required high cata-
lyst loading; in these cases the presence of the strong elec-
tron-donating group slowed down the oxidative addition
of Pd(0) to the aryl bromide (entries 14 and 15).12 The
transesterification of a methoxy carbonyl group was not
observed (entries 22 and 23). Heterocyclic aryl bromides
coupled to form the corresponding sulfide in good yield
(entries 27–29).
In conclusion, we have developed a convenient catalyst
system for C–S cross-coupling.13 The approach does not
require a strong base and tolerates various functional
groups.
Supporting Information for this article is available online at
(9) (a) Correa, A.; Carril, M.; Bolm, C. Angew. Chem. Int. Ed.
2008, 47, 2880. (b) Wu, J.-R.; Lin, C.-H.; Lee, C.-F. Chem.
Commun. 2009, 4450.
(10) Reddy, V. P.; Kumar, A. V.; Swapna, K.; Rao, K. R. Org.
Lett. 2009, 11, 1697.
Synlett 2010, No. 19, 2891–2894 © Thieme Stuttgart · New York