Benzofurans from benzophenones and dimethylacetamide: Copper-promoted cascade formation of furan O1-C2 and C2-C3 bonds under oxidative conditions

Article abstract of DOI:10.1002/anie.201108513

DMA donates: Copper(II) acetate and 8-hydroxyquinoline promote the formation of a benzofuran core through a cascade of copper-catalyzed processes wherein the key carbon atom comes from the dimethylacetamide (DMA) solvent. Strong evidence for the participation of a Wacker cyclization catalyzed solely by copper is provided, not only in the title reaction from benzophenones but also from 2-hydroxy-α-arylstyrene derivatives. Copyright

Full text of DOI:10.1002/anie.201108513

.
Angewandte
Communications
DOI: 10.1002/anie.201108513
Cascade Cyclization
Benzofurans from Benzophenones and Dimethylacetamide: Copper-
À
À
Promoted Cascade Formation of Furan O1 C2 and C2 C3 Bonds
Under Oxidative Conditions**
Marꢀa J. Moure, Raul SanMartin,* and Esther Dominguez*
Dedicated to Professor Carmen Nꢁjera on the occasion of her 60th birthday
Table 1: One-pot approach to benzofurans from benzophenones, and
The benzofuran core is a ubiquitous heterocyclic motif that is
very common in natural products and biologically active
compounds. Among this prolific family of heterocycles, the
3-arylbenzofuran framework can be found in a series of
pharmacologically relevant structures.[1]
functional group tolerance studies.[a]
In the course of our research on copper-catalyzed
oxidative processes, we attempted an intramolecular oxida-
tive O-arylation on ortho-hydroxybenzophenones. Surpris-
ingly, in one of the assays, 3-phenylbenzofuran 2a was isolated
instead of the expected xanthone derivative. We were initially
puzzled by such an unexpected result, as this transformation
was utterly unrelated to the methods for 3-arylbenzofuran
synthesis described in the literature.[2] Moreover, it had
nothing in common with the general entries to the benzofuran
Entry Product
1
Yield[b]
Entry Product
7
Yield[b]
93
80 (75)[c]
2
3
69 (60)[c]
8
9
75 (69)[c]
core, as an unprecedented simultaneous formation of the
[3]
À
À
furan O1 C2 and C2 C3 bonds was involved.
Herein, we present the synthesis of
a
series of
90
39
3-arylbenzofurans and the progress made to gain a more
profound knowledge of the possible pathways that could
explain this novel entry to the benzofuran core. As an
additional proof to support our proposal, an innovative
cyclization of ortho-hydroxy-a-arylstyrenes is also presented.
As shown in Table 1, treatment of 2-hydroxybenzo-
phenone 1a with CuOAc (50 mol%) in the presence of one
atmosphere of oxygen, 8-hydroxyquinoline (8-OQ, 40 mol%)
and potassium carbonate (1 equiv) in N,N-dimethylacetamide
(DMA) at 1408C provided 3-phenylbenzofuran 2a in 80%
yield. An array of assays was performed to optimize the
reaction conditions;[4a] these assays reveal that other bases,
ligands (even closely structurally related ones, such as
sulfoxine), and/or solvents provide negligible results, and
only Cu(OAc)2·H2O and CuI can be used as alternate copper
sources (75% and 53% yields, respectively). The extension of
4
5
53
69
10
11
62 (65)[c]
74
6
71
12
80 (50)[c]
[a] Reaction conditions: Ketone 1, CuOAc (50 mol%), 8-OQ (50 mol%),
K2CO3 (1 equiv) and anhydrous DMA (10 mLmmolÀ1 of 1), 1408C, 24 h.;
DMA=N,N-dimethylacetamide, 8-OQ=8-hydroxyquinoline. [b] Yield of
isolated product. [c] The yields from the reaction using Cu(OAc)2·H2O
(50 mol%) as the copper source are shown in parentheses.
[*] M. J. Moure, Dr. R. SanMartin, Prof. E. Dominguez
Department of Organic Chemistry II, Faculty of Science and
Technology, University of the Basque Country
Sarriena auzoa, z/g 48940 Leioa (Spain)
E-mail: raul.sanmartin@ehu.es
qopdopee@lg.ehu.es
[**] This research was supported by the University of the Basque
Country/Basque Government (Projects GIC10/52/IT-370-10 and
S-PC10UN10) and the Spanish Ministry of Science and Innovation
(CTQ2010-20703). M.J.M. thanks the University of the Basque
Country (UPV/EHU) for a predoctoral scholarship.
the procedure to a number of commercially available or
readily synthesized[4a] diarylketone derivatives 1 afforded the
benzofuran derivatives 2 (displayed in Table 1) bearing alkyl,
alkoxy, heteroaryl, or halogen functional groups. However,
strong electron-withdrawing groups such as nitro or sulfonic
acid on the aryl rings were not tolerated by this procedure.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201108513.
3220
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 3220 –3224

Angewandte
Chemie
Furthermore, the presence of an aryl or heteroaryl ring
attached to the 2-hydroxybenzoyl moiety is a requirement for
this reaction, as o-hydroxyacetophenones and other alkyl
ketones and esters did not react under the above condi-
tions.[4a] Considering the relatively high amount of copper salt
employed, we decided to attempt to recycle it, using oxidative
cyclization to 3-phenylbenzofuran 2a as a model reaction.
After workup and product separation from the initial
reaction, further runs were conducted by just adding the
hydroxyketone 1a and K2CO3 to a DMA solution of the
active catalyst. The second run provided a 64% yield, whereas
a slightly lower 54% was obtained on the third run.
Unfortunately, only traces of the target ketone were observed
in the following runs. It was also possible to perform the
reaction either by using Cu(OAc)2·H2O as an alternative
copper source (for a comparison, see Table 1) or with smaller
amounts of CuOAc (40 mol% and 20 mol%), but in these
cases the above recycling procedure gave significantly poorer
results (69% to 25% to < 5% for 40 mol% CuOAc; 37% to
8% to < 5% for 20 mol% CuOAc; and 75% to 32% to < 5%
for 50 mol% Cu(OAc)2·H2O).
As mentioned above, a literature search revealed a com-
plete lack of precedent for the presented formation of the
benzofuran core. Nevertheless, we undertook mechanistic
studies to elucidate the probable pathways. The reaction
could be initiated from a Cope-type ketene formation
(structure II) from DMA solvent in an oxidizing atmosphere,
or alternatively by an initial addition of the ligand to the
solvent followed by a Cope elimination that generates ketene
hemiketal III (Scheme 1). In both cases, DMA participation is
Scheme 2. Possible pathways for copper-promoted benzofuran forma-
tion.
provide target 2. Pathway B involves a Wacker-type cycliza-
tion[6] of 2-hydroxy-a-phenylstyrene VII (Scheme 2).
Support for pathway A comes from literature examples of
the aerobic epoxidation of olefins.[5] However, most of the
related research to date is limited to multi-metal catalysts
and/or relatively high oxygen pressures.[7] In our case, only
a single copper catalyst would be involved and only under an
atmospheric pressure of oxygen. It should also be pointed out
that the reaction does not proceed in the absence of oxygen.
Pathway B, on the other hand, involves an unprecedented
copper-catalyzed Wacker-type cyclization. Whereas palla-
dium-catalyzed Wacker reactions in the presence or absence
of copper reoxidants are well-known processes in synthetic
chemistry (and many of them are conducted in DMA),[6]
a literature search revealed that no examples of copper-
catalyzed Wacker oxidations have been described so far.
Intrigued by this challenging proposal, ICP-MS analyses of
the copper source employed, the carbonate base, and starting
material 1a were performed, showing that the palladium
content in the reaction mixture was around 10À5 mol%, which
is a homeophatic amount for any Wacker cyclization.[8]
A number of additional experiments were carried out to
shed light on this rather obscure mechanistic crossover. The
first one involved the use of [D9]DMA as solvent. No
deuterated positions were observed in the resulting product
2. A closer look at Scheme 2 ([D9]DMA has been used as
Scheme 1. A tentative proposal for ketene formation from DMA.
clear; other solvents, such as DMF, DMSO, N,N-dimethyl-
formamide dimethyl acetal, MeOH, or AcOEt, provided
negligible results. Formation of ketene-type N,N-dimethyl-
keteniminium ions by thermal elimination of DMA has
already been reported, as has the trapping of such reactive
keteniminium species with hydroxy compounds.[4b,c] Ligand
addition to II would generate III, which could attack the
ketone carbonyl of starting benzophenone 1, thus forming
unsaturated ester V after dehydration (Scheme 2). From this
key intermediate, two alternative routes can be proposed.
Pathway A is based on the participation of epoxides VIa or
VIb, formed either by an epoxidation[5] of V (VIa) or by
a sequential decarboxylation/epoxidation (VIb). Decarbox-
ylation and/or dehydration of intermediate VIII would
Angew. Chem. Int. Ed. 2012, 51, 3220 –3224
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3221

.
Angewandte
Communications
a starting material in both Scheme 1 and Scheme 2 to clarify
this point) shows that the dehydration and decarboxylation
steps (from IV to V, from V to VII, and from VIII to 2) can
provide non-deuterated product 2 by pathway A. In path-
way B, deuterium could be also lost at the Wacker cyclization
step (from VII to 2). 13C-Labeled DMA (with 13C-enriched
acetyl carbon atoms; see carbon atoms C in Scheme 1 and
Scheme 2) was next employed and the corresponding 13C2
labeled product was obtained (Scheme 2) with a similar
enrichment percentage. Further to this unquestionable proof
of the participation of the DMA solvent in the reaction,
a more profitable assay was finally performed, submitting
readily synthesized[9] intermediate VII to the same reaction
conditions.
As shown in Table 2, several 2-hydroxy-a-arylstyrenes 3
were treated with our CuOAc/8-hydroxyquinoline/DMA/O2
system to afford target benzofurans 2 in moderate to good
yields. Halogen, alkyl, and alkoxy functional groups were
again well tolerated under these oxidative conditions.
Because of the difficulty of preparing 2’-substituted
2-hydroxy-a-arylstyrene derivatives,[9] the effect of steric
hindrance on this reaction was not evaluated. No examples
of copper-catalyzed electrophilic addition processes[10] from
2-hydroxystyrenes have been found, and the need for
molecular oxygen to produce the desired reaction outcome
in this case was also significant. Recycling of the DMA phase
containing the promoter was tested with the parent styrene 3a
in a similar procedure to that performed with 1a. Using the
same loading as in the optimized procedure (CuOAc
(50 mol%), 8-OQ (0.4 equiv)), the second run provided
a 51% yield of the target heterocycle 2a, the third a 38%
yield and only traces of 2a were detected in the following
runs.
The participation of phenoxy radicals and their addition
to the alkene moiety might be suggested as an alternative
pathway to a Wacker-type mechanism for the transformation
from intermediate VII (or styrenes 3) to benzofurans 2.
Nevertheless, the presence of stoichiometric amounts of
TEMPO, a known radical scavenger,[11] did not affect the
reaction outcome with either 1a or 3a. Dihydrobenzofuran
derivative 4 (Scheme 3), with the structure of intermediate
Table 2: Formation of the benzofuran core by copper-catalyzed oxidative
cyclization of 2-hydroxy-a-arylstyrene derivatives.[a]
Entry Product
1
Yield[b] Entry Product
Yield[b]
59
77
72
6
7
2
3
83
54
Scheme 3. Detection of 3-hydroxy-3-phenyldihydrobenzofuran 4 in reac-
tion mixtures from 2-hydroxy-a-arylstyrene derivatives, and synthesis of
3-phenylbenzofuran 2a from epoxide 5 and unsaturated acid deriva-
tives 6 and 7.
53
57
8
9
VIII (R2 = H; Scheme 2), was detected in the reaction
between styrene derivative 3a and m-chloroperbenzoic acid
(MCPBA), in an assay intended to obtain the corresponding
epoxide VIb. Unfortunately, 3a provided benzophenone 1a
and a small amount of the aforementioned species 4. Even
treatment of [2-(1-phenylvinyl)phenoxy]tert-butyldimethyl-
silane, which is readily prepared by silylation of 3a, with
MCPBA afforded 4 along with only traces of the expected
epoxide. A Johnson–Corey–Chaykovsky reaction[12] per-
formed on 1a afforded epoxide 5, which, under oxidative
cyclization conditions (O2, CuOAc, 8-OQ, K2CO3, DMA,
1408C), provided benzofuran 2a (Scheme 3). From all of
these assays it was clear that, although unstable, epoxide-type
intermediates such as VI were closely related to dihydrofuran
intermediates VIII and benzofurans 2 (Scheme 2). Finally, the
participation of unsaturated acid and lactone derivatives as
4
5
50
62
57
10
[a] Reaction conditions: Alkene 3, CuOAc (50 mol%), 8-OQ (50 mol%),
K2CO3 (1 equiv), and anhydrous DMA (10 mLmmolÀ1 of 3), 1408C,
24 h.; DMA=N,N-dimethylacetamide, 8-OQ=8-hydroxyquinoline.
[b] Yield of isolated product.
3222
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 3220 –3224

Angewandte
Chemie
Hayes, J. Baffic, Y. S. Chao, A. Elbrecht, L. J. Kelly, M. H. Lam,
intermediates (V and V’, Scheme 2) in the mechanism was
also examined and confirmed. 4-Phenylcoumarin 6 was easily
prepared (81%) by reaction of ortho-hydroxybenzophenone
1a with dimethylmalonate,[13] and then hydrolyzed[14] to give
3-(2-hydroxyphenyl)-3-phenylacrylic acid 7. Both lactone 6
and carboxylic acid 7 were then submitted to our oxidative
conditions, providing the corresponding benzofuran 2a with
good yields (80% and 78%, respectively; Scheme 3).
A. Schmidt, S. Sahoo, J. Wang, S. D. Wright, P. Xin, G. Zhou,
D. E. Moller, C. P. Sparrow, Endocrinology 2002, 143, 2548;
e) M. Saitoh, J. Kunitomo, E. Kimura, H. Iwashita, Y. Uno, T.
Onishi, N. Uchiyama, T. Kawamoto, T. Tanaka, C. D. Mol, D. R.
Dougan, G. P. Textor, G. P. Snell, M. Takizawa, F. Itoh, M. Kori,
J. Med. Chem. 2009, 52, 6270; f) V. Srivastava, A. S. Negi, J. K.
Kumar, U. Faridi, B. S. Sisodia, M. P. Darokar, S. Luqman, S. P. S.
Khanuja, Bioorg. Med. Chem. Lett. 2006, 16, 911.
[2] Previously, 3-arylbenzofurans were synthesized either by dehy-
dration of o-hydroxybenzyl ketones under acidic conditions:
a) R. Adams, L. Whitaker, J. Am. Chem. Soc. 1956, 78, 8; b) K.
Kalyanasundaram, S. Rajagopalan, S. Swaminathan, Tetrahe-
dron Lett. 1980, 21, 4391; or by dehydrative cyclization of a-
(phenoxy)alkyl ketones: c) J. B. Wright, J. Org. Chem. 1960, 25,
1867; d) R. Royer, E. Bisagni, C. Hudry, A. Cheutin, M.-L.
Desvoye, Bull. Soc. Chim. Fr. 1963, 1003; e) C. Pene, P.
Demerseman, A. Cheutin, R. Royer, Bull. Soc. Chim. Jpn.
1971, 44, 749; f) T. Horaguchi, H. Iwanami, T. Tanaka, E.
Hasegawa, T. Shimizu, J. Chem. Soc. Chem. Commun. 1991, 44;
however, more recently, the palladium-catalyzed cyclization of
aryl acetylenes has been employed: g) T. Ishikawa, T. Miyahara,
M. Asakura, S. Higuchi, Y. Miyauchi, S. Saito, Org. Lett. 2005, 7,
1211; h) A. R. Katritzky, Y. Ji, Y. Fang, I. Prakash, J. Org. Chem.
2001, 66, 5613; i) P. J. Seo, H. D. Choi, B. W. Son, J. Korean
Chem. Soc. 2002, 46, 384; j) M. C. Willis, D. Taylor, A. T.
Gillmore, Org. Lett. 2004, 6, 4755; k) M. A. Honey, A. J. Blake,
I. B. Campbell, B. D. Judkins, C. J. Moody, Tetrahedron 2009, 65,
8995; l) A. I. Roshchin, S. M. Kel’chevski, N. A. Bumagin, J.
Organomet. Chem. 1998, 560, 163; m) S. N. Aslam, P. C. Steven-
son, S. J. Phythian, N. C. Veitch, D. R. Hall, Tetrahedron 2006,
62, 4214; n) S. S. Hosseiny Davarani, N. M. Najafi, S. Ramyar, L.
Masoumi, M. Shamsipur, Chem. Pharm. Bull. 2006, 54, 959; for
other approaches to 3-arylbenzofurans, see: o) I. Kim, S. H. Lee,
S. Lee, Tetrahedron Lett. 2008, 49, 6579; p) J. M. Patel, S. S.
Soman, J. Heterocycl. Chem. 2007, 44, 945; q) K. C. Nicolaou,
S. A. Snyder, A. Bigot, J. A. Pfefferkorn, Angew. Chem. 2000,
112, 1135; Angew. Chem. Int. Ed. 2000, 39, 1093; r) A. V. Gutnov,
A. V. Butin, V. T. Abaev, G. D. Krapivin, V. E. Zavodnik,
Molecules 1999, 4, 204; s) T. Suzuki, T. Horagugchi, T. Shimizu,
T. Abe, Bull. Chem. Soc. Jpn. 1983, 56, 2762; t) R. Romagnoli,
P. G. Baraldi, M. D. Carrion, C. L. Cara, O. Cruz-Lopez, M.
Tolomeo, S. Grimaudo, A. Di Cristina, M. R. Pipitone, J.
Balzarini, N. Zonta, A. Brancale, E, Hamel, Bioorg. Med.
Chem. 2009, 17, 6862.
In summary, two synthetically useful entries to the
benzofuran core have been presented, starting from commer-
cially available or readily synthesized 2-hydroxybenzo-
phenones and 2-hydroxy-a-arylstyrene derivatives. Both
approaches are based on the same oxidative reaction
conditions, which involve the use of molecular oxygen at
atmospheric pressure and CuOAc/8-hydroxyquinoline/
K2CO3 in DMA. Insights into the mechanistic pathways that
may take place in such unprecedented transformations is
provided, suggesting DMA activation to generate ketene
derivatives and either epoxidation under oxygen atmosphere
or Wacker cyclization as copper-catalyzed key steps. Accord-
ing to the proposed mechanism, DMA is the source of the
carbon unit required for this new approach to benzofurans
from 2-hydroxybenzophenones by the cascade formation of
À
À
O1 C2 and C2 C3 bonds. The participation of 2-hydroxy-a-
arylstyrene intermediates is demonstrated by the fact that the
latter can be effectively used as substrates, thus leading to
benzofurans under similar oxidative conditions. The occur-
rence of other proposed intermediates, such as unsaturated
acids, lactones, epoxides, and dihydrofuran derivatives is also
discussed and demonstrated.
Experimental Section
General procedure for the synthesis of benzofurans
2 from
2-hydroxybenzophenones 1 or 2-hydroxy-a-arylstyrenes 3: A mixture
of the 2-hydroxybenzophenone or 2-hydroxy-a-arylstyrene
1
3
(0.252 mmol), copper(I) acetate (15 mg, 0.123 mmol), 8-hydroxy-
quinoline (15 mg, 0.103 mmol), and K2CO3 (35 mg, 0.252 mmol) in
anhydrous DMA (2.5 mL) was stirred in a round-bottom flask for
24 h at 1408C under an oxygen atmosphere. The reaction mixture was
cooled to room temperature, then H2O (5.0 mL) was added and the
resulting aqueous suspension was extracted with ethyl acetate (3 ꢀ
5 mL). The organic layer was washed with H2O (15 mL) and brine
(15 mL), dried over anhydrous Na2SO4, and concentrated in vacuo.
The crude product was purified by flash chromatography using ethyl
acetate/n-hexane 1:9 as eluent, to provide pure benzofuran 2.
[3] For the simultaneous formation of more than one bond in
À
À
benzofuran synthesis, see: O1 C2 and C3 C3a: a) X. Guo, R.
Yu, H. Li, Z. Li, J. Am. Chem. Soc. 2009, 131, 17387; b) L. Cires,
H. Ofenberg, C. Craita, Org. Prep. Proced. Int. 2001, 33, 361;
c) Y. T. Reddy, P. N. Reddy, M. K. Rao, B. Rajitha, S. M. Reddy,
M. Sridevi, Indian J. Chem. Sect. B 2001, 40B, 479; d) B. J.
Morrison, O. C. Musgrave, Tetrahedron 2002, 58, 4255; e) G. C.
Kulkarni, S. N. Karmarkar, S. L. Keldar, M. S. Wadia, Tetrahe-
dron 1988, 44, 5189; f) H. D. Choi, P. J. Seo, B. W. Son, J. Korean
Chem. Soc. 2001, 45, 500; g) S. Spyroudis, J. Org. Chem. 1986, 51,
3453; h) R. Huisgen, G. Binsch, H. Kçnig, Chem. Ber. 1964, 97,
Received: December 2, 2011
Published online: February 9, 2012
Keywords: benzofurans · copper · cyclization ·
.
homogeneous catalysis · oxidation
À
À
2884; C7a O1 and C3 C3a: i) Y. Inukai, T. Sonoda, H.
Kobayashi, Bull. Chem. Soc. Jpn. 1979, 52, 2657; j) M. V.
Gorelik, E. V. Mishina, Zh. Org. Khim. 1983, 19, 2185; k) Y.
Terao, T. Satoh, M. Miura, M. Nomura, Bull. Chem. Soc. Jpn.
1999, 72, 2145; l) B. L. Flynn, E. Hamel, M. K. Jung, J. Med.
Chem. 2002, 45, 2670.
[1] For iantheran A, see: a) Y. Okamoto, M. Ojika, S. Suzuki, M.
Murakami, Y. Sakagami, Bioorg. Med. Chem. 2001, 9, 179; b) H.
Greve, S. Meis, M. U. Kassack, S. Kehraus, A. Krick, A. D.
Wright, G. M. Kçnig, J. Med. Chem. 2007, 50, 5600; for
PBFuranAA, see: c) C. Santini, G. D. Berger, W. Han, R.
Mosley, K. MacNaul, J. Berger, T. Doebber, M. Wu, D. E.
Moller, R. L. Tolman, S. P. Sahoo, Bioorg. Med. Chem. Lett.
2003, 13, 1277; see also: d) J. G. Menke, K. L. MacNaul, N. S.
[4] a) For full details on the synthesis of precursors, optimization
assays, and other substrates assayed, as well as a discussion of
alternative copper sources and the role of water, see the
Supporting Information; b) A. Potthast, T. Rosenau, H. Sixta,
P. Kosma, Tetrahedron Lett. 2002, 43, 7757; see also: c) R.
Angew. Chem. Int. Ed. 2012, 51, 3220 –3224
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3223

.
Angewandte
Communications
Martinez, M. C. Huff, M. A. Barteau, Appl. Catal. A 2000, 200,
79.
ChemCatChem 2011, 3, 174; c) L. Hu, L. Shi, H. Hong, M. Li, Q.
Bao, J. Tang, J. Ge, J. Lu, X. Cao, H. Gu, Chem. Commun. 2010,
46, 8591; d) L. Yang, J. He, Q. Zhang, Y. Wang, J. Catal. 2010,
276, 76.
[5] Some interesting references on the copper-catalyzed epoxida-
tion of olefins can be found in: a) S. Minakata, K. Inaki, M.
Komatsu, J. Oleo Sci. 2002, 51, 549; b) J. Chisem, I. C. Chisem,
J. S. Rafelt, D. J. Macquarrie, J. H. Clark, Chem. Commun. 1997,
2203; c) N. Komiya, T. Naota, Y. Oda, S.-I. Murahashi, J. Mol.
Catal. A 1997, 117, 121; d) J. Liang, Q. Tang, G. Meng, H. Wu, Q.
Zhang, Y. Wang, Chem. Lett. 2004, 33, 1140; e) R. M. Lambert,
F. J. Williams, R. L. Cropley, A. Palermo, J. Mol. Catal. A 2005,
228, 27.
[6] For some examples of the Wacker reaction leading to furan and
benzofuran frameworks, see: a) M. Soledade, C. Pedras, M.
Hossain, Bioorg. Med. Chem. 2007, 15, 5981; b) F. Alonso, D.
Sꢁnchez, T. Soler, M. Yus, Adv. Synth. Catal. 2008, 350, 2118;
c) K. Takenaka, S. C. Mohanta, M. L. Patil, C. V. Laxman Rao, S.
Takizawa, T. Suzuki, H. Sasai, Org. Lett. 2010, 12, 3480; d) K.
Takenaka, Y. Tanigaki, M. L. Patil, C. V. Laxman Rao, S.
Takizawa, T. Suzuki, H. Sasai, Tetrahedron: Asymmetry 2010,
21, 767; e) A. Wang, H. Jiang, J. Org. Chem. 2010, 75, 2321; f) T.
Mitsudome, T. Umetani, N. Nosaka, K. Mori, T. Mizugaki, K.
Ebitani, K. Kaneda, Angew. Chem. 2006, 118, 495; Angew.
Chem. Int. Ed. 2006, 45, 481; g) T. Mitsudome, K. Mizumoto, T.
Mizugaki, K. Jitsukawa, K. Kaneda, Angew. Chem. 2010, 122,
1260; Angew. Chem. Int. Ed. 2010, 49, 1238; for a synthesis of
3-phenylbenzofuran from 2-hydroxy-a-phenylstyrene using
PdCl2/Cu(OAc)2, see Ref. [6a]. For the same reaction performed
in the absence of copper, see: h) G. Casiraghi, G. Casnati, G.
Puglia, G. Sartori, G. Terenghi, Synthesis 1977, 122.
[8] To the best of our knowledge, palladium catalyst loadings higher
than 2 ꢀ 10À1 mol% are required for Wacker cyclization; see
ref. [6] for more details. See also: a) B. W. Michel, A. M.
Camelio, C. N. Cornell, M. S. Sigman, J. Am. Chem. Soc. 2009,
131, 6076; b) B. Weiner, A. Baeza, T. Jerphagnon, B. L. Feringa,
J. Am. Chem. Soc. 2009, 131, 9473.
[9] a) M. Yamaguchi, M. Arisawa, K. Omata, K. Kabuto, M.
Hirama, T. Uchimaru, J. Org. Chem. 1998, 63, 7298; b) M.
Yamaguchi, A. Hayashi, M. Hirama, J. Am. Chem. Soc. 1995,
117, 1151.
[10] For some metal-catalyzed electrophilic additions to alkenes, and
related reactions leading to benzofuran derivatives, see: a) V.
Spꢂziale, D. H. Giao, A. Lattes, J. Heterocycl. Chem. 1978, 15,
225; b) K. Orito, T. Hatakeyama, M. Takeo, H. Suginome, M.
Tokuda, Synthesis 1997, 23.
[11] For example, see: P. J. Wright, A. M. English, J. Am. Chem. Soc.
2003, 125, 8655.
[12] J. A. Ciaccio, A. L. Drahus, R. M. Meis, C. T. Tingle, M. Smrtka,
R. Geneste, Synth. Commun. 2003, 33, 2135.
[13] For the preparation of 4-phenylcoumarin from the same
reagents using microwave irradiation, see: J. Crecente-Campo,
M. P. Vazquez-Tato, J. A. Seijas, Eur. J. Org. Chem. 2010, 4130.
[14] For the hydrolysis of a structurally related lactone, see: E. L.
Grimm, C. Brideau, N. Chauret, C.-C. Chan, D. Delorme, Y.
Ducharme, D. Ethier, J.-P. Falgueyret, R. W. Friesen, J. Guay, P.
Hamel, D. Riendeau, C. Soucy-Breau, P. Tagari, Y. Girard,
Bioorg. Med. Chem. Lett. 2006, 16, 2528.
[7] a) X. Zhang, Z.-H. Li, J. Wang, M.-Y. Huang, Y.-Y. Jiang, Polym.
Adv. Technol. 1999, 10, 483; b) A. Seubsai, M. Kahn, S. Senkan,
3224
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 3220 –3224