Cationic Pd(II)-Catalyzed fujiwara-moritani reactions at room temperature in water

Article abstract of DOI:10.1021/ol100331h

Figure presented Pd^II-catalyzed Fujiwara-Moritani reactions can be carried out without external acid at room temperature and in water as the only medium. A highly active cationic Pd^II catalyst, [Pd(MeCN) ₄](BF₄)₂, easily activates aromatic C-H bonds to produce electron-rich cinnamates in good yields.

Full text of DOI:10.1021/ol100331h

ORGANIC
LETTERS
2010
Vol. 12, No. 9
1972-1975
Cationic Pd(II)-Catalyzed
Fujiwara-Moritani Reactions at Room
Temperature in Water
Takashi Nishikata and Bruce H. Lipshutz*
Department of Chemistry and Biochemistry, UniVersity of California,
Santa Barbara, California 93106
lipshutz@chem.ucsb.edu
Received February 17, 2010
ABSTRACT
PdII-catalyzed Fujiwara-Moritani reactions can be carried out without external acid at room temperature and in water as the only medium. A
highly active cationic PdII catalyst, [Pd(MeCN)4](BF4)2, easily activates aromatic C-H bonds to produce electron-rich cinnamates in good
yields.
C-H activation reactions are very much in focus. Exchanges
between aromatic C-H bonds and arenes, aryl halides,
olefins, and heteroaromatics continue to be extensively
investigated.1 The Fujiwara-Moritani reaction (Scheme 1),
group4 and a meta-selective Fujiwara-Moritani reaction.5
Nonetheless, traditional Fujiwara-Moritani reactions that can
be conducted in the absence of external acid, as well as at
ambient temperatures, have yet to be reported.6 Typically,
acids such as HOAc, TFA, and TsOH are used to accelerate
these cross-couplings, whereas water has inhibitory
properties.6b The catalyst is oftentimes palladium acetate,
where acetate (or carboxylate) presumably participates in
aromatic proton abstraction (Scheme 2).7 Thus, Pd(OAc)2
has the dual role of electrophilic activation of the arene
and intramolecular deprotonation in either a six-membered
transition state (A) or alternative (B).8 Oxidative addition
of a metal-substrate complex to an aromatic C-H bond
is another possibility.9 Although electrophilic substitution
of an aromatic C-H bond with cationic palladium has
Scheme 1
first reported in 1967,2 is one representative of such
Pd-catalyzed couplings. Previous reports on C-H alkeny-
lation reactions indicated that not only are elevated temper-
atures (80-160 °C) and anhydrous acidic conditions re-
quired, but high pressures of CO or O2 as an oxidizing agent
may also be important.1a,3 Related recent developments of
note include reactions with arenes bearing an ortho-directing
(3) (a) Wu, J.; Cui, X.; Chen, L.; Jiang, G.; Wu, Y. J. Am. Chem. Soc.
2009, 131, 13888. (b) Aouf, C.; Thiery, E.; Le Bras, J.; Muzart, J. Org.
Lett. 2009, 11, 4096. (c) Cheng, D.; Gallagher, T. Org. Lett. 2009, 11, 2639.
(d) Cho, S. H.; Hwang, S. J.; Chang, S. J. Am. Chem. Soc. 2008, 130,
9254. (e) Dams, M.; De Vos, D. E.; Celen, S.; Jacobs, P. A. Angew. Chem.,
Int. Ed. 2003, 42, 3512. (f) Yokota, T.; Tani, M.; Sakaguchi, S.; Ishii, Y.
J. Am. Chem. Soc. 2003, 125, 1476. (g) Weissman, H.; Song, X.; Milstein,
D. J. Am. Chem. Soc. 2001, 123, 337. (h) Matsumoto, T.; Yoshida, H. Chem.
Lett. 2000, 29, 1064.
(1) See recent reviews: (a) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu,
J.-Q. Angew. Chem., Int. Ed. 2009, 48, 5094. (b) Li, C.-J. Acc. Chem. Res.
2009, 42, 335. (c) Kakiuchi, F.; Kochi, T. Synthesis 2008, 3013. (d) Seregin,
I. V.; Gevorgyan, V. Chem. Soc. ReV. 2007, 36, 1173. (e) Ishiyama, T.;
Miyaura, M. Pure Appl. Chem. 2006, 78, 1369. (f) Nevado, C.; Echavarren,
A. M. Synthesis 2005, 167, and references therein.
(4) For example: (a) Cai, G.; Li, Y.; Wan, X.; Shi, Z. J. Am. Chem. Soc.
2007, 129, 7666. (b) Amatore, C.; Cammoun, C.; Jutand, A. AdV. Synth.
Catal. 2007, 349, 292. (c) Lee, G. T.; Jiang, X.; Prasad, K.; Repicˇ, O.;
Blacklock, T. J. AdV. Synth. Catal 2005, 347, 1921. See also refs 1 and 3.
(5) Zhang, Y.-H.; Shi, B.-F.; Yu, J.-Q. J. Am. Chem. Soc. 2009, 131, 5072.
(2) (a) Fujiwara, Y.; Moritani, I.; Danno, S.; Asano, R.; Teranishi, S.
J. Am. Chem. Soc. 1969, 91, 7166. (b) Fujiwara, Y.; Moritani, I.; Matsuda,
M.; Teranishi, S. Tetrahedron Lett. 1968, 9, 633. (c) Moritani, S.; Fujiwara,
Y. Tetrahedron Lett. 1967, 8, 1119.
10.1021/ol100331h  2010 American Chemical Society
Published on Web 04/05/2010

been proposed,1,3,6d,g,j use of strongly Lewis acid dicationic
PdII for C-H activation is very rare.4a
Table 1. Optimization of Reaction Conditionsa
Scheme 2
acid
(equiv)
yield
(%)
entry
catalyst
Pd(OAc)2
additives (equiv)
1
2
3
4
5
6
7
8
9
BQ (1.5)
BQ (1.5)
BQ (1.5)
BQ (1.5)
BQ (1.5)
BQ (1.0)
none
p-TsOH (0.5) 39
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
CSA (0.5)
AcOH (6)
TFA (1)
30
16
trace
HBF4 aq (1) 47
HBF4 aq (5) 63
HBF4 aq (5)
0
AgNO3 (2.0)
HBF4 aq (5) trace
BQ (1.0), AgNO3 (2.0) HBF4 aq (5) 72b
BQ (1.0), AgNO3 (2.0) HBF4 aq (5) 95
10 Pd(OAc)2
11 Pd(OAc)2
12 [Pd(MeCN)4](BF4)2 BQ (1.0), AgNO3 (2.0) none
BQ (1.0), AgNO3 (2.0) none
trace
Recently,
a
weak dicationic palladium species,
66b
[Pd(MeCN)2](OTs)2, has been reported as an effective
catalyst for C-H activation of ureas under an atmosphere
of CO leading to products of carbonylation.10 In these cases,
the presence of TsOH was essential, and simple acetanilide
derivatives gave poor results. Herein, we disclose new
technology for effecting Fujiwara-Moritani reactions on
anilide derivatives that not only take place at room temper-
ature and in water as the only medium, but most notably
without addition of external acid (Scheme 3).
13 [Pd(MeCN)4](BF4)2 BQ (1.0), AgNO3(2.0) none
85
a Conducted at rt for 20 h in 2 wt % PTS/water and 10 mol % catalyst,
additives, 3-methoxyacetanilide (1a), and n-butyl acrylate (2a, 2 equiv).
b Reaction was conducted “on water”.
1-alkenylated product (3a), derived from the reaction of
3-methoxyacetanilide (1a) with n-butyl acrylate (2a) in
water (entries 1-6). In the presence of 1,4-benzoquinone
(BQ) and surfactant PTS (polyoxyethanyl R-tocopheryl
sebacate),11 C-H activation takes place. Among the acids
investigated, excess HBF4 gave the best yield (entry 6).
BQ was critical, without which the reaction essentially
did not take place in water (entry 7). Use of an alternative
oxidizing agent, such as a silver salt, was of no conse-
quence (entry 8). Ultimately, it was found that a mixture
of additives consisting of BQ and AgNO3 in PTS/water
gave a 95% yield of the desired product 3a (entry 10).
As expected, acid plays an important role in the reaction
catalyzed by Pd(OAc)2 (entry 11). Remarkably, the
commercially available dicationic palladium salt
[Pd(MeCN)4](BF4)2 also smoothly catalyzes the reaction
at room temperature without a large excess of external
acid (entry 13). None of the product from a potentially
competitive 1,4-addition pathway was observed.12,13 Sur-
factants other than PTS were also studied but found to be
less effective: Brij 35 (42%); Triton X-100 (48%); Solutol
(65%). In the absence of PTS, the corresponding “on water”
reactions were not competitive (entries 9, 12).
Scheme 3
Initially, as illustrated in Table 1, reactions under acidic
conditions catalyzed by Pd(OAc)2 led to low yields of
(6) C-H activation at room temperature is rare. (a) Reaction of an arene with
benzoquinone: Zhang, H.-B.; Liu, L.; Chen, Y.-J.; Wang, D.; Li, C.-J. AdV.
Synth. Catal 2006, 348, 229. (b) Fujiwara-Moritani reaction: Boele, M. D. K.;
van Strijdonck, G. P. F.; de Vries, A. H. M.; Kamer, P. C. J.; de Vries,
J. G.; van Leeuwen, P. W. M. N. J. Am. Chem. Soc. 2002, 124, 1586. (c)
C-H borylation: Ishiyama, T.; Takagi, J.; Hartwig, J. F.; Miyaura, N. Angew.
Chem., Int. Ed. 2002, 41, 3056. (d) Reaction of an arene forming multiple bonds:
Jia, C.; Piao, D.; Oyamada, J.; Lu, W.; Kitamura, T.; Fujiwara, Y. Science
2000, 287, 1992. (e) Methoxycarbonylation: see also ref 10. Reaction with indoles:
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Deprez, N. R.; Kalyani, D.; Krause, A.; Sanford, M. S. J. Am. Chem. Soc.
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Chem., Int. Ed. 2009, 48, 1830.
(11) (a) Nishikata, T.; Abela, A. R.; Lipshutz, B. H. Angew. Chem.,
Int. Ed. 2010, 49, 781. (b) Nishikata, T.; Lipshutz, B. H. J. Am. Chem.
Soc. 2009, 131, 12103. (c) Krasovskiy, A.; Duplais, C.; Lipshutz, B. H.
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Org. Lett., Vol. 12, No. 9, 2010
1973

The scope of this transformation is illustrated in Table
2. Reactions of m-alkoxy-functionalized anilide derivatives
proceed smoothly with acrylates 2 containing a variety
of alkyl chains to afford products regiospecifically in
70-96% yields (entries 1-12). Isomeric p-alkoxy ana-
reactions under these conditions gave the corresponding
vinylated products in good isolated yields (entries 14, 15).
Multisubstituted anilides also participated at room tem-
perature, leading to a variety of substituted arenes (entries
9-12).
Although ortho-directed C-H activation remains a very
attractive approach to cross-coupling chemistry, it can
result in double functionalization, with reactions often-
times occurring at both sites ortho to the directing group.1
In such situations, 2-substituted arenes need to be
employed so as to avoid this undesired competing
pathway. Since an ortho-substituent in a product such as
4 appears to sterically prevent these secondary couplings,
this can be used to advantage. Hence, our standard
conditions for C-H activation lead to a single, regiospe-
cifically ortho-positioned product of C-H substitution (4;
Scheme 4).
Table 2. Fujiwara-Moritani Reactions with Anilide
Derivativesa
Scheme 4. Selective Coupling
One proposed pathway to account for these cationic
palladium(II)-catalyzed reactions is offered in Scheme 5,
although details await further investigation. Initial elec-
trophilic attack by cationic PdII6g,j,14 occurs on an aromatic
C-H bond in 1 with the aid of the directing group,
proceeding via Wheland-like species 515 to generate mono-
cationic species 6. The resulting product 3 is obtained after
carbopalladation by 6 of acrylate 2, followed by ꢀ-hydride
Scheme 5. Proposed Mechanism
a Run at rt for 20 h in 2 wt % PTS/water (1 mL) and 10 mol %
[Pd(MeCN)4](BF4)2, BQ (1 equiv), AgNO3 (2 equiv), anilide 1 (0.25 mmol),
and acrylate ester 2 (2 equiv). b 48 h.
logues were found to be unreactive. A pivalamide leading
to product 3n is slower-reacting, presumably due to
difficulty in forming a monocationic species from dica-
tionic Pd (entry 13). Although urea derivatives are reported
to react only in the presence of excess acid,10 their
1974
Org. Lett., Vol. 12, No. 9, 2010

elimination. Pd0 is then oxidized back to PdII by 1,4-
benzoquinone and silver salts, notwithstanding the potential
for BQ to competitively ligate the active cationic PdII
catalyst.16
Acknowledgment. Financial support provided by the NIH
(GM 86485) is gratefully acknowledged, as is Johnson
Matthey for providing catalyst [Pd(MeCN)4](BF4)2 used in
this study.
Supporting Information Available: Experimental pro-
cedures and characterization of all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
In conclusion, Fujiwara-Moritani reactions of anilides
can now be run without external acids, at room temper-
ature, and in water as the only medium. A general strategy
based on highly reactive dicationic palladium catalysts for
the synthesis of valued cinnamates has been established.
OL100331H
(17) Typical Procedure. Anilide 1 (0.25 mmol), acrylate ester 2 (0.5
mmol), AgNO3 (0.5 mmol), 1,4-benzoquinone (0.25 mmol), and
[Pd(MeCN)4](BF4)2 (0.025 mmol) were sequentially added in air to a
reaction tube equipped with a stir bar and capped with a septum. An aqueous
solution containing PTS (1.0 mL, 2 wt %) was added by syringe, and the
reaction mixture was vigorously stirred for 20 h. After completion, the
contents of the flask were quenched with aq NaHCO3 and extracted with
EtOAc. The solution obtained was filtered through a plug of silica gel and
anhydrous MgSO4 and concentrated by rotary evaporation. The residue was
purified by flash chromatography, eluting with hexane/EtOAc to afford the
desired product.
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