oxidative cyclization, but the substrate is still limited to
electron-rich arenes6 and such a method could not be
applied to synthesize benzofuranones. Obviously, the de-
velopment of a transition-metal-catalyzed direct cycliza-
tion to synthesize benzofuranones from easily available
carboxylic acids could be desirable and has never been
approached.
Over the past decade, extensive efforts have been made
to develop methods to functionalize aromatic CÀH bonds
directly to construct CÀC,7 CÀN,8 and CÀO9 bonds.
Many of these reactions were assisted by directing groups,
which played dual roles to assist chelation and subse-
quently promote further functionalization. Especially,
the use of carboxylic acid as a directing group for CÀH
activation, developed by Yu9 and other research groups,10
has shown its advantages. Recently, Liu and Yoshikai
first reported a Pd-catalyzed cyclization to approach the
dibenzo[b,d]furan11a,b and dihydrobenzofuran11c through
the CÀH activation/intramolecular CÀO formation se-
quence. However, the Pd-catalyzed intermolecular car-
boxylation of CÀH bonds has been well developed. Yet,
the carboxyl directed CÀH bond activation and subse-
quent intramolecular cyclization offer a distinct challenge,
because of (1) the large energy gap between the highest
occupied molecular orbital (HOMO) of the PdÀO bond
of carboxylate and the lowest unoccupied molecular
orbital (LUMO) of the PdÀC bond, (2) the substantial
ionic character of the PdÀO bond, and (3) the stability
of palladacycles.12 We report herein the first successful
example of a straightforward and versatile method to
obtain functionalized benzofuranones through palladium-
catalyzed intramolecular oxidative aromatic CÀO bond
formation from readily available 2-arylacetic acids.
Figure 1. Natural bioactive products containing benzofuranone
rings.
combination of Pd(OAc)2 and K2HPO4, which was re-
garded as an efficient catalytic system in the carboxyl
directed CÀH/CÀO cyclization.12 We surveyed a wide
range of oxidants to promote CÀO reductive elimination
from putative Pd(II), Pd(III),13 or Pd(IV)14 intermediates.
However, no desired product 2a was observed (entries
1À6). We further tested PhI(OAc)2, a generally effective
oxidant for the Pd(II)ÀPd(IV) catalytic pathway.15 To our
delight, 53% of the desired product was obtained (entry 7).
Encouraged by this result, we extensively screened various
bases and found that CsOAc was the most effective one
(entries 8À13). The extra addition of AgOAc further
increased the yield to 65% (entry 14). Other silver salts,
such as Ag2O and Ag2CO3, were not efficient (entries
16À17). The combination of NaOAc and CsOAc supplied
the best result in the presence of AgOAc (entry 15).
Obviously, without Pd catalysis, the reaction did not work
(entry 18), showing a completely different pathway from
the previously reported work, through the oxidative cycli-
zation pathway.6
We began our study with 1a as the model substrate
(Table 1). The first attempt was conducted with the
(6) G, Y.; Xue, K. Tetrahedron Lett. 2010, 51, 192.
(7) For recent reviews, see: (a) Bouffard, J.; Itami, K. Top. Curr.
Chem. 2010, 292, 231. (b) Colby, D. A.; Bergman, R. G.; Ellman, J. A.
Chem. Rev. 2010, 110, 624. (c) Bras, L. L.; Muzart, J. Chem. Rev. 2011,
111, 1170. (d) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215. (e)
Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011, 40,
5068. (f) Yu, D.-G.; Li, B.-J.; Shi, Z.-J. Tetrahedron 2012, 68, 5130.
(8) For CÀN bond formation, see: (a) Tsang, W. C. P.; Zheng, N.;
Buchwald, S. L. J. Am. Chem. Soc. 2005, 127, 14560. (b) Chen, X.; Hao,
X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem. Soc. 2006, 128, 6790. (c)
Thu, H.-Y.; Yu, W.-Y.; Che, C.-M. J. Am. Chem. Soc. 2006, 128, 9048.
(d) Inamoto, K.; Saito, T.; Katsuno, M.; Sakamoto, T.; Hiroya, K. Org.
Lett. 2007, 9, 2931. (e) Tan, T.; Hartwig, J. F. J. Am. Chem. Soc. 2010,
132, 3676. (f) Grohmann, C.; Wang, H.; Glorius, F. Org. Lett. 2012, 14,
656. For CÀO bond formation, see: (g) Desai, L. V.; Stowers, K. J.;
Sanford, M. S. J. Am. Chem. Soc. 2008, 130, 13285. (h) Zhang, Y.-H.;
Yu, J.-Q. J. Am. Chem. Soc. 2009, 131, 14654. (c) Sun, C.-L.; Liu, J.;
Wang, Y.; Zhou, X.; Li, B.-J.; Shi, Z.-J. Synlett 2011, 7, 883.
With the optimized conditions in hand, we explored the
substrate scope (Scheme 1). Significant steric and electron-
ic effects of the substituents on the reactivity were ob-
served. For biaryl substrates, electron-neutralgroups, such
i
t
as Me, Pr, and Bu (2aÀe), afforded the corresponding
products in good yields. Both electron-donating groups
(MeO, 2f) and electron-withdrawing groups(CF3, 2g) were
tolerated on the substituted aryl ring. Ortho-substituted
normal phenyl acetic acid is also efficient (2l). Moreover,
the reaction could be conducted in the presence of halo
substituents, thus allowing further functionalization through
(9) For selected references, see: (a) Wang, D. H.; Engle, K. M.; Shi,
B. F.; Yu, J.-Q. Science 2010, 327, 315. (b) Engle, K. M.; Mei, T.-S.;
Wasa, M.; Yu, J.-Q. Acc. Chem. Res. 2012, 45, 788.
(10) For selected references, see: (a) Fraunhoffer, K. J.; Prabagaran,
N.; Sirois, L. E.; White, M. C. J. Am. Chem. Soc. 2006, 128, 9032. (b)
Chiong, H. A.; Pham, Q.-N.; Daugulis, O. J. Am. Chem. Soc. 2007, 129,
9879. (c) Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2007, 9, 1407.
(11) (a) Xiao, B.; Gong, T.- J.; Liu, Z.-J.; Liu, J.-H.; Luo, D.-F.; Xu,
J.; Liu, L. J. Am. Chem. Soc. 2011, 133, 9250. (b) Wei, Y.; Yoshikai, N.
Org. Lett. 2011, 13, 5504. (c) Wang, X.; Lu, Y.; Dai, H.-X.; Yu, J.-Q.
J. Am. Chem. Soc. 2010, 132, 12203.
(13) (a) Powers, D. C.; Ritter, T. Nat. Chem. 2009, 1, 302. (b) Deprez,
N. R.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131, 11234.
~
(14) For a recent review of Pd(IV) chemistry, see: Muniz, K. Angew.
Chem., Int. Ed. 2009, 48, 9412.
ꢀ
(12) Novak, P.; Correa, A.; Gallardo-Donaire, J.; Martin, R. Angew.
(15) Yoneyama, T.; Crabtree, R. H. J. Mol. Catal. A: Chem. 1996,
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