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DOI: 10.1002/cctc.201400091
Palladium(II)/Polyoxometalate-Catalyzed Direct
Alkenylation of Benzofurans under Atmospheric Dioxygen
Qiufeng Huang,*[a, b] Shaojia Ke,[a] Lin Qiu,[a] Xiaofeng Zhang,[a] and Shen Lin*[a, c]
An efficient and selective C2 alkenylation of benzofurans was
performed by using Pd(OAc)2 combined with a catalytic
amount of 11-molybdovanadophosphoric acid (H4PMo11VO40)
under an atmosphere of dioxygen. N-Acetylglycine (Ac-Gly-OH)
was observed to be an effective additive for the olefination
reaction.
esters and ethers by using Ag2CO3 (1 equiv.) as the oxidant.[10e]
In addition, Miura et al. reported the Pd-catalyzed CÀH alkeny-
lation/decarboxylation of benzofuran-2-carboxylic acid by
using Cu(OAc)2·H2O (2 equiv.) as the oxidant.[10f] However, each
of these procedures suffers from the requirement of high Pd
loadings or the need for stoichiometric amounts of a terminal
oxidant such as copper(II) salts, silver(I) salts, or benzoquinone.
The development of a new catalytic system that uses ecologi-
cally benign oxidants such as dioxygen would be highly desir-
able. Recently, it was demonstrated that the high activation
energy for the direct oxidation by O2 could be circumvented
by the use of polyoxometalates (POMs).[14] However, this effi-
cient method often requires harsh reaction conditions such as
the use of a strong acid solvent[14d–f] and high O2 pressure.[14a]
Herein, we report an efficient Pd(OAc)2/POM-catalyzed C2 alke-
nylation of benzofurans in DMF by using atmospheric dioxy-
gen as the terminal oxidant.
The benzofuran motif is present in a wide range of natural and
unnatural compounds that exhibit a variety of important bio-
logical activities.[1] As such, derivatives of benzofuran have
found use as versatile intermediates in organic synthesis, and
the study of methods to prepare and functionalize benzo-
furans continues to be an active area of research.[2]
Transition-metal-catalyzed CÀH bond functionalization of
benzofurans is a practical synthetic tool,[3] as it eliminates the
need for preparing benzofuryl halides,[4] benzofuryl triflates,[5]
benzofurylstannanes,[6] benzofurylboronic acids,[7] and benzo-
furylzinc compounds,[8] which are intermediates in some ben-
zofuran functionalization strategies. The Fujiwara–Moritani re-
action,[9] which is the palladium-catalyzed direct oxidative cou-
pling of aromatic substrates with alkenes, is among the most
effective and straightforward strategies used to introduce
a side chain into benzofurans.[10] This reaction was first per-
formed by using stoichiometric amounts of palladium,[11] but it
was also shown to take place with catalytic amounts of palladi-
um.[12] In recent years, a variety of procedures for the CÀH alke-
nylation of aromatic heterocycles have been successfully devel-
oped.[13] For example, Kasahara et al.[10a] and Fujiwara et al.[10b,c]
reported the Pd(OAc)2-mediated reaction of benzofurans with
a variety of olefins. Fujiwara et al. also presented the oxidative
coupling of benzofurans with olefins in the presence of catalyt-
ic amounts of palladium acetate and benzoquinone with tert-
butyl hydroperoxide as the oxidant.[10d] Liu et al. developed
a direct PdII-catalyzed olefination of benzofurans with allylic
To investigate the use of POM/O2 as an oxidant for the
Pd(OAc)2-catalyzed alkenylation of benzofurans, we chose ben-
zofuran (1a) and styrene (2a) as model substrates to optimize
the reaction conditions. Selected results from these initial stud-
ies are summarized in Table 1. First, a variety of POMs were
evaluated. The best yield of 3a was obtained if the heteropoly
acid H4PMo11VO40 was used as the reoxidation catalyst (Table 1,
entry 1). The use of other heteropoly acids such as
H9PMo6V6O40, H3PMo12O40, and H5PMo10V2O40 resulted in a signif-
icant decrease in the yield (Table 1, entries 4–6), whereas
(NH4)5H4PMo6V6O40 and (NH4)4PMo11VO40 did not catalyze the
coupling reaction at all (Table 1, entries 2 and 3). External
bases, which are believed to act as proton abstractors, have
been observed to be beneficial to palladium-catalyzed CÀH
cleavage reactions. Thus, the effect of base was examined.
Other alkali metal salts were less effective than Na2CO3
(Table 1, entries 1 and 7–9). Notably, additives played a crucial
role in the reaction. Removing Hacac from the reaction mixture
resulted in a lower yield (6%; Table 1, entry 10), dibenzoylme-
thane showed no benefit over Hacac (Table 1, entry 11), and
DMAP and Boc-Leu-OH seemed to inhibit the reaction (Table 1,
entries 12 and 13). However, in the presence of Ac-Gly-OH,
a type of monoprotected amino acid, the coupling of 1a with
2a afforded 3a in 50% yield under O2 pressure (1 atm; Table 1,
entry 14). Monoprotected amino acids were recently devel-
oped as powerful additives in PdII-catalyzed oxidative CÀH
cross-coupling reactions by Yu et al.[15] A further increase in
yield was obtained by changing the solvent from DMSO to
DMF; in this case, the product was formed in 86% yield
(Table 1, entry 20). Other solvents such as TFA, tAmOH, NMP,
and 1,4-dioxane significantly attenuated the reaction or caused
it to fail altogether (Table 1, entries 15–19). The reaction of 1a
[a] Prof. Dr. Q. Huang, S. Ke, L. Qiu, X. Zhang, Prof. Dr. S. Lin
College of Chemistry & Chemical Engineering
Fujian Normal University
350007 Fuzhou (P.R. China)
[b] Prof. Dr. Q. Huang
Key Laboratory of Coal to Ethylene Glycol and Its Related-Technology
Chinese Academy of Sciences
350002 Fuzhou (P.R. China)
[c] Prof. Dr. S. Lin
Fujian Key Laboratory of Polymer Materials
350007 Fuzhou (P.R. China)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201400091.
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2014, 6, 1531 – 1534 1531
Huang, Qiufeng
