LETTER
Propylene Oxide Assisted Sonogashira Coupling Reaction
3241
Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley: New
York, 1998, Chap. 5. (f) Brandsma, L.; Vasilevsky, S. F.;
Verkruijsse, H. D. Application of Transition Metal Catalysts
in Organic Synthesis; Springer-Verlag: Berlin, 1998, Chap.
10. (g) Nicolaou, K. C.; Sorensen, E. J. Classics in Total
Synthesis; Wiley-VCH: Weinheim Germany, 1996, 582.
(h) Tsuji, J. Palladium Reagents and Catalysts; Wiley:
Chichester, 1995, 168. (i) Rossi, R.; Carpita, A.; Bellina, F.
Org. Prep. Proced. Int. 1995, 27, 127. (j) Sonogashira, K.
In Comprehensive Organic Synthesis, Vol. 3; Trost, B. M.,
Ed.; Pergamon: New York, 1991, Chap. 2.4.
Table 4 PO-Assisted Sonogashira Coupling of Alkyne 3 with Iodo-
benzene
O
PhI (110 mol%), 1 (2.5 mol%)
CuI (5 mol%), Ph3P (2.5 mol%)
Ph
scavenger, DMF, r.t., 48 h
3
O
O
Ph
Ph
+
(3) For recent representative advances in Sonogashira or
Sonogashira-type cross-coupling, see: (a) Novak, Z.; Szabo,
A.; Repasi, J.; Kotschy, A. J. Org. Chem. 2003, 68, 3327.
(b) Batey, R. A.; Shen, M.; Lough, A. J. Org. Lett. 2002, 4,
1411. (c) Hundertmark, T.; Littke, A. F.; Buchwald, S. L.;
Fu, G. C. Org. Lett. 2000, 2, 1729. (d) Alami, M.; Crousse,
B.; Ferri, F. J. Organomet. Chem. 2001, 624, 114.
(e) Soheili, A.; Albaneze-Walker, J.; Murry, J. A.; Dormer,
P. G.; Hughes, D. L. Org. Lett. 2003, 5, 4191. (f) Mori, A.;
Kawashima, J.; Shimada, T.; Suguro, M.; Hirabayashi, K.;
Nishihara, Y. Org. Lett. 2000, 2, 2935. (g) Anastasia, L.;
Negishi, E. Org. Lett. 2001, 3, 3111. (h) Cheng, J.; Sun, Y.;
Wang, F.; Guo, M.; Xu, J.-H.; Pan, Y.; Zhang, Z. J. Org.
Chem. 2004, 69, 5428. (i) Arques, A.; Aunon, D.; Molina, P.
Tetrahedron Lett. 2004, 45, 4337. (j) Ma, D.; Liu, F. Chem.
Commun. 2004, 1934. (k) Elangovan, A.; Wang, Y.-H.; Ho,
T.-I. Org. Lett. 2003, 5, 1841. (l) Thorand, S.; Krause, N.
J. Org. Chem. 1998, 63, 8551.
(4) To the best of our knowledge, PO has not been used in C–C
bond formation. For the sole relevant precedent (in C–S
bond formation), see: Moreau, X.; Campagne, J.-M.
J. Organomet. Chem. 2003, 687, 322.
(5) (a) For an example of Sonogashira reaction with Et3N as
both the solvent and the base in preparing diphenylacetylene,
see: Perner, R. J.; Gu, Y.-G.; Lee, C.-H.; Bayburt, E. K.;
McKie, J.; Alexander, K. M.; Kohlhaas, K. L.; Wismer,
C. T.; Mikusa, J.; Jarvis, M. F.; Kowaluk, E. A.; Bhagwat,
S. S. J. Med. Chem. 2003, 46, 5249. (b) General
Ph
Ph
4
5
Entry Scavenger
Time (h) 4/5
Yield [4 + 5 (%)]a
1
2
3
PO (5 equiv)
24
48
24
94:6
57
80
88
PO (5 equiv)
Et3N (excess)
69:31
0:100
a Isolated yield.
as the scavenger, our protocol should in general be a better
choice for base-sensitive substrates.
In conclusion, a PO-assisted Sonogashira cross-coupling
reaction has been developed. The unique base-free feature
of the current protocol has extended the scope of Sono-
gashira reaction to some base-sensitive substrates. Other
related transition-metal-catalyzed cross-coupling reac-
tions might also benefit from the current PO strategy. The
research results along these lines will be reported in due
course.
Supporting Information for this article is available online at
Procedure: The Batey Pd-carbene complex 1 (2.5 mol%),
CuI (5 mol%), Ph3P (2.5 mol%) and DMF (2 mL) were
added to a dry 10-mL septum-capped round-bottomed flask
under a nitrogen atmosphere. Aryl iodide (2 mmol), alkyne
(110 mol%), and PO (5 equiv) were then added to the above
mixture. While the mixture was stirred, the flask was cooled
to –78 °C, vacuumed, and charged with nitrogen. This
process was repeated for three times. After the mixture was
warmed to 25 °C, stirring was continued at that temperature
for 48 h. The mixture was diluted with H2O and extracted
with E2O. The organic extracts were combined, washed with
brine, dried (MgSO4), filtered, and concentrated to give a
residue, which was purified by flash column
Acknowledgment
Financial support was provided by the grants from NSFC
(90713007, 20772141, 20625204, 20632030), and MOST_863
(2006AA09Z405, 2006AA09Z446).
References and Notes
(1) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron
Lett. 1975, 50, 4467. (b) Cassar, L. J. Organomet. Chem.
1975, 93, 253. (c) Dieck, H. A.; Heck, F. R. J. Organomet.
Chem. 1975, 93, 259.
(2) For reviews, see: (a) Doucet, H.; Hierso, J.-C. Angew.
Chem. Int. Ed. 2007, 46, 834. (b) Chinchilla, R.; Najera, C.
Chem. Rev. 2007, 107, 874. (c) Wang, Y.-F.; Deng, W.; Liu,
L.; Guo, Q.-X. Chin. J. Org. Chem. 2005, 25, 8.
chromatography on silica gel.
(6) Ma, Y.; Song, C.; Jiang, W.; Wu, Q.; Wang, Y.; Liu, X.;
Andrus, M. B. Org. Lett. 2003, 5, 3317.
(7) Chow, H.-F.; Wan, C.-W.; Low, K.-H.; Yeung, Y.-Y. J. Org.
Chem. 2001, 66, 1910.
(8) Tang, B.-X.; Wang, F.; Li, J.-H.; Xie, Y.-X.; Zhang, M.-B.
J. Org. Chem. 2007, 72, 6294.
(d) Negishi, E.; Anastasia, L. Chem. Rev. 2003, 103, 1979.
(e) Sonogashira, K. In Metal-Catalyzed Cross-Coupling
Synlett 2008, No. 20, 3239–3241 © Thieme Stuttgart · New York