and LiebeskindÀSrogl cross-coupling employing the reac-
tions of thioesters with organic boronic acids has been well
documented.10,11 Ketene dithioacetals and 1,3-dithianes,12
as an important class of synthetic reagents, have drawn
continuous interest in the synthesis of heterocycles,13 carbo-
cycles, and aromatic compounds.14 Although metal-free
organic transformations of ketene dithioacetals and 1,3-
dithianes have been well explored, only a few transition-
metal-catalyzed systems have recently been realized in
this aspect,15,16 presumably due to easy poisoning of the
dithioalkyl moieties in the dithio substrates to a transition
metal catalyst. We recently reported Pd-mediated trans-
formations of R-oxo ketene dithioacetals (1)15a and found
that 1 may be used as gem-dihaloolefin-type vinyl building
blocks. Herein, we disclose efficient Pd(0)-catalyzed,
Cu(I)-mediated mono- and double arylation and alkenyla-
tion of 1 with aryl- and alkenylboronic acids (2) via oxo
directing LiebeskindÀSrogl cross-coupling.
Table 1. Screening of Reaction Conditions for the Cross-Coupling
of R-Oxo Ketene Dithioacetal (1a) with Phenylboronic Acid (2a)a
The reaction of R-oxo ketene dithioacetal (1a) with
phenylboronic acid (2a) was initially investigated to screen
the reaction conditions (Table 1). With Pd(PPh3)4 as the
catalyst and Cs2CO3 as the base, the reaction seldom
occurred in THF at 50 °C (entry 1). By means of copper(I)
(9) (a) Ishizuka, K.; Seike, H.; Hatakeyama, T.; Nakamura, M.
J. Am. Chem. Soc. 2010, 132, 13117. (b) Creech, G. S.; Kwon, O.
J. Am. Chem. Soc. 2010, 132, 8876. (c) Kobatake, T.; Fujino, D.; Yoshida,
S.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2010, 132, 11838.
ꢀ
(10) (a) Prokopcova, H.; Kappe, C. O. Angew. Chem., Int. Ed. 2009,
48, 2276. (b) Liebeskind, L. S.; Srogl, J.; Savarin, C.; Polanco, C. Pure
Appl. Chem. 2002, 74, 115.
a Conditions: 1a (0.3 mmol), 2a (0.45 mmol), catalyst (7.5 mol %),
[Cu] mediator (0.6 mmol), Cs2CO3 (0.6 mmol), solvent (3 mL), 50 °C, 0.1
MPa N2. b Yields based on 1a. c Determined by GC analysis. d Molar
ratios. e Without a base. f Using Na2CO3 base. g Using K2CO3 base.
h Isolated yields of 3aa in parentheses. i At 25 °C.
(11) For selected recent reports on LiebeskindÀSrogl cross-coupling,
see: (a) Liebeskind, L. S.; Yang, H.; Li, H. Angew. Chem., Int. Ed. 2009,
48, 1417. (b) Yang, H.; Li, H.; Wittenberg, R.; Egi, M.; Huang, W. W.;
Liebeskind, L. S. J. Am. Chem. Soc. 2007, 129, 1132. (c) Zhang, Z. H.;
Liebeskind, L. S. Org. Lett. 2006, 8, 4331. (d) Yu, Y.; Liebeskind, L. S.
J. Org. Chem. 2004, 69, 3554. (e) Kusturin, C. L.; Liebeskind, L. S.;
Neumann, W. L. Org. Lett. 2002, 4, 983. (f) Savarin, C.; Srogl, J.;
Liebeskind, L. S. Org. Lett. 2001, 3, 91. (g) Liebeskind, L. S.; Srogl, J.
J. Am. Chem. Soc. 2000, 122, 11260.
(12) (a) Liu, J.; Wang, M.; Han, F.; Liu, Y. J.; Liu, Q. J. Org. Chem.
2009, 74, 5090. (b) Kobatake, T.; Yoshida, S.; Yorimitsu, H.; Oshima,
K. Angew. Chem., Int. Ed. 2010, 49, 2340. (c) Kim, H.; Park, Y.; Hong,
J. Y. Angew. Chem., Int. Ed. 2009, 48, 7577.
(13) For selected recent reports, see: (a) Li, Y. F.; Xu, X. X.; Tan, J.;
Xia, C. Y.; Zhang, D. W.; Liu, Q. J. Am. Chem. Soc. 2011, 133, 1775.
(b) Zhang, L. J.; Xu, X. X.; Tan, J.; Pan, L.; Xia, W. M.; Liu, Q. Chem.
Commun. 2010, 46, 3357. (c) Tan, J.; Xu, X. X.; Zhang, L. J.; Li, Y. F.;
Liu, Q. Angew. Chem., Int. Ed. 2009, 48, 2868. (d) Misra, N. C.; Ila, H.
J. Org. Chem. 2010, 75, 5195. (e) Kumar, S.; Ila, H.; Junjappa, H. J. Org.
Chem. 2009, 74, 7046. (f) Kumar, S.; Peruncheralathan, S.; Ila, H.;
Junjappa, H. Org. Lett. 2008, 10, 965. (g) Rao, H. S. P.; Sivakumar, S.
J. Org. Chem. 2006, 71, 8715.
(14) For selected recent reports, see: (a) Wang, M.; Fu, Z. Q.; Feng,
H.; Dong, Y.; Liu, J.; Liu, Q. Chem. Commun. 2010, 46, 9061. (b) Hu,
J. L.; Zhang, Q.; Yuan, H. J.; Liu, Q. J. Org. Chem. 2008, 73, 2442. (c) Bi,
X. H.; Dong, D. W.; Liu, Q.; Pan, W.; Zhao, L.; Li, B. J. Am. Chem. Soc.
2005, 127, 4578. (d) Yadav, A. K.; Ila, H.; Junjappa, H. Eur. J. Org.
Chem. 2010, 338. (e) Yadav, A. K.; Peruncheralathan, S.; Ila, H.;
Junjappa, H. J. Org. Chem. 2007, 72, 1388.
thiophene-2-carboxylate (CuTC)17 as the catalyst/media-
tor the reaction did not efficiently proceed either (entry 2).
However, under the conditions for a typical Liebeskind-
Srogl cross-coupling reaction, treatment of 1a with 2a
resulted in a 93% yield for products 3aa and 4a (3aa:4a =
90:10) (entry 3). Although a base is not indispensable, it
obviously promoted the reaction (entries 3À6). Com-
1
pound (E)-3aa was formed as the only product by H
NMR analysis.18 Other Pd sources only exhibited moder-
ate to good catalytic activity (entries 7À11). CuI also
behaved as an effective mediator but exhibited a lower
efficiency (entries 12À16). THF seems to be the suitable
solvent for the reaction (entries 17À21). At ambient tem-
perature, the reaction smoothly took place, selectively
forming 3aa in 89% yield (entry 22).
Under the optimized conditions, the protocol scope was
explored (Table 2). The reactions of 1 with 2 predomi-
nantly or exclusively formed products of type (E)-3, sug-
gesting a remarkable directing effect from the R-oxo group
of 1. Methyl, methoxy, tert-butyl, formyl, chloro, fluoro,
nitro, and bromo can be tolerated as the substituents in the
substrates, and the desired trisubstituted olefins 3 were
obtained in good to excellent yields up to 98%. The steric
(15) (a) Yu, H. F.; Jin, W. W.; Sun, C. L.; Chen, J. P.; Du, W. M.; He,
S. B.; Yu, Z. K. Angew. Chem., Int. Ed. 2010, 49, 5792. (b) Yu, H. F.; Yu,
Z. K. Angew. Chem., Int. Ed. 2009, 48, 2929.
(16) (a) Wang, Y. M.; Bi, X. H.; Li, W. Q.; Li, D. H.; Zhang, Q.; Liu,
Q.; Ondon, B. S. Org. Lett. 2011, 13, 1722. (b) Yuan, H. J.; Wang, M.;
Liu, Y. J.; Wang, L. L.; Liu, J.; Liu, Q. Chem.;Eur. J. 2010, 16, 13450.
(c) Liang, D. Q.; Wang, M.; Bekturhun, B.; Xiong, B. B.; Liu, Q. Adv.
Synth. Catal. 2010, 352, 1593. (d) Liu, Y. J.; Wang, M.; Yuan, H. J.; Liu,
Q. Adv. Synth. Catal. 2010, 352, 884. (e) Yuan, H.-J.; Wang, M.; Liu,
Y.-J.; Liu, Q. Adv. Synth. Catal. 2009, 351, 112.
(17) Zhang, S. J.; Zhang, D. W.; Liebeskind, L. S. J. Org. Chem. 1997,
62, 2312.
(18) Nishio, T.; Omote, Y. J. Chem. Soc., Perkin Trans. 1 1981, 934.
Org. Lett., Vol. 13, No. 16, 2011
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