Synthesis of aryl ketones by palladium(II)-catalyzed decarboxylative addition of benzoic acids to nitriles

Article abstract of DOI:10.1002/anie.201003009

An efficient, sustainable method for the preparation of aryl ketones from ortho-substituted benzoic acids proceeds through their decarboxylation to generate an aryl-palladium species, followed by addition to a nitrile and hydrolysis of the intermediate ketimine.

Full text of DOI:10.1002/anie.201003009

Angewandte
Chemie
DOI: 10.1002/anie.201003009
Coupling Reactions
Synthesis of Aryl Ketones by Palladium(II)-Catalyzed Decarboxylative
Addition of Benzoic Acids to Nitriles
Jonas Lindh, Per J. R. Sjꢀberg, and Mats Larhed*
Ketones are a common functionality in many types of organic
compounds for example, pharmaceuticals and natural prod-
ucts. In 2004, Larock reported novel reactions of arenes or
arylboronic acids with nitriles to generate aryl ketones by
hydrolysis of the intermediate ketimine.[1] This pioneering
work on carbon–transition-metal bond insertions into polar
Myers.[12,13] Furthermore, a number of reactions employing
bimetallic catalysts have been developed, which can effi-
ciently promote the decarboxylation of a broad range of non-
activated aryl carboxylates.[14]
Intrigued by the possibility of further broadening the
scope of these useful aryl palladium precursors, we decided to
investigate the possibility of preparing aryl ketones from
benzoic acids and nitriles using palladium(II) catalysis
(Scheme 1).
À
carbon nitrogen triple bonds has since been followed by a
number of related reports.[2] As useful as the reported
transformations are, there are possible drawbacks: all of
these reported methods use arenes or arylboronic acids to
generate the aryl palladium species and often require
relatively harsh reaction conditions.[1] Arenes are generally
cheap and widely available, but suffer from poor regiocon-
trol.[1] Arylboronic acids, on the other hand, offer regiocon-
trol, but are comparably expensive, are not as widely
available, and may be unstable.[3]
Scheme 1. General reaction scheme.
Carboxylic acids are cheap, non-toxic, widely commer-
cially available, stable, and are easily prepared.[4] Although
metal-mediated decarboxylations have long been known[5]
and sporadically reported in the literature,[6] they did not
emerge as synthetically useful processes until recently. In the
last couple of years, discoveries have shown that it is possible
to use certain benzoic acids as direct aryl palladium pre-
cursors, thus resulting in the release of gaseous carbon dioxide
and the desired aryl palladium complex.[4,7,8] As decarbox-
ylation is an environmentally friendly and efficient way of
generating aryl palladium intermediates, this finding is of
great importance in the endeavor towards more sustainable
chemistry. Using a palladium(II) catalyst, the scope of
accessible benzoic acids might be somewhat limited, as they
appear to require certain activating ortho substituents.[4,7,9]
However, work by Goossen et al. has enabled copper- and
silver-catalyzed protodecarboxylations of a wide range of
benzoic acids by using phenanthroline ligands.[10]
As the use of the carboxylic acid functional group is very
common in organic synthesis, there are reported methods for
transforming benzoic acids into aryl ketones.[15] Traditionally,
these multistep methods require harsh reaction conditions,
are tedious to perform, and generally involve stoichiometric
amounts of metal reagents, such as lithium reagents.[16]
In the last decade, a number of attractive new cross-
coupling methods for preparing aryl ketones from carboxylic
acid derivatives and boronic acids have been published. These
mild procedures require pre-formation of thioesters[17] or
in situ activation of the carboxylic acid by stoichiometric
additives to form anhydrides[18] and employ relatively expen-
sive boronic acids as coupling partners. Recently, a new
method to synthesize aryl ketones from a-oxocarboxylic acid
salts and aryl bromides was reported,[19] in which a-oxocar-
boxylic acid salts are decarboxylated by a copper catalyst to
generate acyl copper species and then arylated with aryl
bromide using a palladium catalyst. A potential limitation of
these methods is the difficulty of using alkylboronic acids or
alkyl halides in cross-couplings, which essentially limits the
scope to only aryl coupling partners. By utilizing nitriles
instead, the reaction scope is extended to afford high yielding
and low-cost reactions with both aryl and alkyl coupling
partners. Herein, we report our initial results towards devel-
oping a facile new catalytic intermolecular one-pot reaction to
afford aryl ketones from benzoic acids and nitriles.
The recent advancements in palladium(II)-catalyzed
decarboxylations have been successfully employed in a
number of Suzuki- and Heck-type reactions in the last
couple of years, foremost by the groups of Goossen[4,11] and
[*] J. Lindh, Prof. M. Larhed
Organic Pharmaceutical Chemistry
Department of Medicinal Chemistry, Uppsala University
BMC, Box-574, 75123 Uppsala (Sweden)
Fax : (+46)18-471-4474
Based on earlier work within our group[20] involving
palladium(II)-catalyzed oxidative Heck[21] reactions, a mono-
metallic test reaction was performed using Pd(O2CCF3)2 and
the dmphen (2,9-dimethyl-1,10-phenanthroline; Table 1, 4 f)
ligand as the catalytic system, 2,6-dimethoxybenzoic acid
(Table 1, 1a) as the substrate, and acetonitrile as the reactant/
solvent.[22] After 30 minutes of microwave (MW) heating,[23]
the results were promising, as the aryl methyl ketone (Table 1,
E-mail: Mats@orgfarm.uu.se
Dr. P. J. R. Sjꢀberg
Department of Physical and Analytical Chemistry
Uppsala University (Sweden)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201003009.
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Table 1: Ligand screen.
idine (4c), dmphen (4 f), and 2,9-dimethyl-4,7-diphenyl-1,10-
phenanthroline (4g) were superior. In no case was the
intermediate imine detected by GC-MS or LC-MS. Based
on the yield of isolated product, 6-methyl-2,2’-bipyridine (4c)
was selected as the optimal ligand for further investigation of
the reaction scope. Prolonging the exposure to microwave
irradiation from 30 to 60 minutes and increasing the catalyst
loading from 4 to 8 mol% improved the yield from 73 to 80%.
Increasing the temperature above 1308C led to formation of
palladium black and poor yields. Lowering the reaction
temperature led to prolonged reaction times to reach full
conversion and very slow product formation was observed at
808C. The reactions could be safely carried out in a heating
block at 1008C, whereas higher temperatures required the use
of a microwave reactor owing to the build-up of pressure in
the sealed vessels. Unfortunately, the results from employing
a bimetallic catalyst system (Cu/Pd or Ag/Pd) were disap-
pointing, resulting in very limited product formation.[10,14,25]
The addition of 1.2 equivalents of para-benzoquinone, as a
reoxidant of palladium, had no beneficial effect on the yield,
thereby indicating that the formation of palladium(0) is not an
issue under these reaction conditions.[26] Addition of 1 equiv-
alent of acid (TFA or HOAc) hindered the reaction and led to
formation of palladium black as did the addition of 1 equiv-
alent of base (Et3N or K2CO3).
Ligand
Yield
[%][a]
4a
4b
16
32
73
80[b]
50[c]
71[d]
63[e]
4c
4d
4e
36
18
4 f
68
To optimize the desired formation of the aryl ketones 3,
several different reaction conditions were examined for each
nitrile (2) and benzoic acid (1; Table 2). To investigate the
scope of the reaction with respect to the nitrile, four
additional nitriles (2b-e) were tested. Nitriles 2b and 2c
worked well, providing 3b and 3c respectively (Table 2,
entries 2 and 3). Benzonitrile (2d) proved to be a poor solvent
or reactant for 1a, and provided only 20% of isolated product
3d (Table 2, entry 4). Benzyl cyanide (2e) gave a satisfying
yield of the product 3e (Table 2, entry 5).
To further investigate the scope of the reaction, a number
of different ortho-substituted benzoic acids were reacted with
acetonitrile to generate the corresponding aryl methyl
ketones (Table 2, entries 6–19). Interestingly, acetonitrile,
whilst being the simplest and cheapest nitrile, has been
scarcely employed in the related couplings of arenes and
boronic acids to nitriles.[1] Trisubstituted 1b worked well,
providing a useful 71% of product 3 f (Table 2, entry 6).
Ethoxy-substituted 1c also gave a good yield of product 3g
(74%), as did the corresponding methoxy-substituted 1d,
which afforded 70% of 3h (Table 2, entries 7 and 8). Bromo-
substituted 3i was isolated in 61%, without any trace of
4g
4h
67
0
4i
19[f]
19
–
–
[a] Yield of isolated product, >95% pure by GC/MS. Reaction con-
ditions: A 5 mL Pyrex glass vial was charged with 2,6-dimethoxybenzoic
acid (0.5 mmol), Pd(O2CCF3)2 (0.02 mmol), ligand (0.024 mmol), H2O
(200 mL), and MeCN (2 mL). The vial was capped in air and exposed to
microwave heating for 30 min at 1308C. [b] Pd(O2CCF3)2 (0.04 mmol), 6-
methyl-2,2’-bipyridine (0.048 mmol) and exposed to MW heating for
60 min at 1308C. [c] Heated in a heating block at 1008C for 48 h.
[d] Same as [c] but with Pd(O2CCF3)2 (0.04 mmol), 6-methyl-2,2’-bipyr-
idine (0.048 mmol). [e] Pd(OAc)2 (0.04 mmol) used instead of Pd-
(O2CCF3)2. [f] 100 mL dimethyl sulfoxide was added. MW=microwave.
3a) was isolated in 50% yield by in situ hydrolysis of the
intermediate ketimine. A few different palladium(II) salts
were tested, of which Pd(O2CCF3)2 was the most successful.[24]
A ligand screen was performed that employed seven different
bidentate nitrogen ligands (Table 1, 4a–g), a bidentate
phosphine ligand (Table 1, 4h), dimethyl sulfoxide (4i), and
a ligand-free reaction. Phosphine ligand 4h was unsuitable for
the transformation and did not provide any of the desired
product. Dimethyl sulfoxide, which had been successfully
employed by Zhou and Larock in reactions of arenes or
arylboronic acids with nitriles to generate aryl ketones,[1] was
not an efficient ligand for this transformation, providing only
19% of isolated 3a. Interestingly, ligandless conditions
provided the same low yield as with dimethyl sulfoxide.
Among the bidentate nitrogen ligands, 6-methyl-2,2’-bipyr-
dehalogenation as
a result of palladium(0) activation
(Table 2, entry 9). Product 3j was isolated in an excellent
yield of 91% (Table 2, entry 10). In an attempt to scale-up the
reaction, from 0.5 mmol to 10.0 mmol scale, the yield dropped
to 67% (Table 2, entry 10). Benzoic acid 1g provided a
disappointing 26% of product 3k (Table 2, entry 11). Inter-
estingly, ortho-fluoro-substituted 1h was a useful substrate
and provided the isolated product 3l in 63% yield (Table 2,
entry 12).[27] Importantly, 1i provided a good amount of 3m
(85%) when hydrolyzed with formic acid, but a low yield of
only 11% in the absence of an additional hydrolysis step
(Table 2, entry 13). Sterically hindered ketimines are known
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Table 2: Palladium(II)-catalyzed reactions of benzoic acids and nitriles.
À
À
Entry
1
Ar COOH
R
Product
Yield
[%][a]
Entry
11
Ar COOH
R
Product
Yield
[%][a]
94[b]
78[c]
90[d]
88[e]
86[f]
Me
(2a)
Me
(2a)
26[g]
20[f]
1a
3a
1g
3k
80[g]
77[f]
Me
(2a)
2
3
4
5
6
1a
1a
1a
1a
1b
Et (2b) 3b
Pr (2c) 3c
Ph (2d) 3d
12
13
14
15
16
1h
1i
3l
3m
3n
3o
3p
63[f]
66[g]
73[f]
Me
(2a)
11[b]
85[f]
Me
(2a)
25[g]
27[f]
20[g]
1j
67[b]
61[g]
90[f]
CH2Ph
3e
50[g]
73[f]
Me
(2a)
1k
1l
(2e)
57[b]
61[g]
62[c]
71[f]
57[b]
57[g]
84[f]
Me
3 f
Me
(2a)
(2a)
50[b]
66[g]
74[f]
Me
3g
Me
(2a)
7
8
1c
1d
17
18
1m
1n
3q
3r
62[f]
51[f]
(2a)
60[b]
59[g]
70[f]
Me
3h
Me
(2a)
(2a)
58[b]
54[g]
61[c]
45[f]
Me
3i
Me
(2a)
9
1e
1 f
19
1o
3s
53[f]
(2a)
63[b]
76[g]
91[f]
67[h]
Me
3j
10
(2a)
[a] Yield of isolated product, >95% pure by GC/MS. [b] A 5 mL Pyrex glass vial was charged with ArCOOH (0.5 mmol), Pd(O2CCF3)2 (0.10 mmol), 6-
methyl-2,2’-bipyridine (0.12 mmol), H2O (200 mL), and nitrile (2 mL). The vial was capped in air and heated in a heating block at 1008C for 48 h.
[c] Same as [b] but exposed to microwave heating for 60 min at 1308C. [d] Same as [c] with the subsequent addition of 1 mL 2m HCl and heating at
1008C for 16 h. [e] Same as [c] but with subsequent addition of 1 mL formic acid and heating at 1008C for 1 h. [f] Same as [e] but with Pd(O2CCF3)2
(0.04 mmol), 6-methyl-2,2’-bipyridine (0.048 mmol). [g] Same as [c] but with Pd(O2CCF3)2 (0.04 mmol), 6-methyl-2,2’-bipyridine (0.048 mmol). [h] A
20 mL Pyrex glass vial was charged with ArCOOH (10.0 mmol), Pd(O2CCF3)2 (0.8 mmol), 6-methyl-2,2’-bipyridine (0.96 mmol), H2O (2.0 mL), and
MeCN (10.0 mL). The vial was capped in air and exposed to microwave heating for 60 min at 1308C, with subsequent addition of 5 mL formic acid and
heating at 1008C for 60 min.
to be stable and can be difficult to hydrolyze into their
corresponding ketones,[1,28] and, as shown in Table 2, addi-
tional hydrolysis through the addition of 1 mL of formic acid
and heating at 1008C for 1 hour often improved the yields of
the isolated aryl methyl ketones. Naphthyl derivative 1j
worked poorly and gave only 27% of product 3n (Table 2,
entry 14). Five different heteroaromatic benzoic acids 1k–o
were tested, and provided their corresponding aryl methyl
ketones 3o–s in 51–90% yield (Table 2, entries 15–19). The
fact that only ortho-functionalized aromatic acids reacted
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Figure 1. ESI/MS-(+) spectrum for the reaction of 1a and MeCN with assigned PdII intermediates.
successfully is in accordance with previous examples of
monometallic palladium(II)-catalyzed decarboxylative pro-
cesses.[4,7]
To examine the reaction mechanism, an electrospray
ionization mass spectrometry (ESI/MS)[29] study was per-
formed. ESI/MS is considered a soft MS ionization technique
as it promotes few fragmentation products and is therefore a
valuable tool in the analysis of catalytic intermediates and
organometallic complexes.[30]
In this study, ESI/MS analysis was conducted to detect
cationic palladium-containing reaction intermediates in ongo-
ing reactions. The reaction shown in Table 2, entry 1 (1008C,
48 h) was chosen for our mechanistic investigation. An
aliquot was withdrawn from the reaction mixture after
6 hours and then diluted 10-fold with acetonitrile. The ESI/
MS-(+) spectrum was immediately recorded by scanning the
first quadrupole (Q1) of a triple-quadrupole instrument.
Several groups of peaks with m/z signals corresponding to the
characteristic isotopic pattern of monopalladium complexes
were observed, whilst only a limited number of non-palla-
dium-containing cations were detected (Figure 1). Based on
the m/z signals in the MS mode, and MS/MS of the selected
signals, structures for the intermediates were proposed.[31] The
detected classes of intermediates were assigned letters (A–D)
based on their plausible role in the reaction. The correspond-
ing ESI/MS-(À) study was also performed, but no anionic
palladium complexes were observed.
Scheme 2. Proposed mechanistic hypothesis supported by MS-
detected cationic palladium complexes.
nitrile group to form complex C, which is probably a fast
process given the large excess of nitrile; 4) 1,2-carbopallada-
tion of the nitrile to form ketimine complex D; 5) protonation
of the ketimine by the benzoic acid to afford the free ketimine
and a palladium(II) species.
In conclusion, we have reported a new palladium(II)-
catalyzed method that allows for the rapid synthesis of aryl
ketone derivatives from ortho-functionalized benzoic acids
and low-cost nitriles. This efficient and environmentally
benign reaction produces gaseous CO2 and ammonium
hydroxide as the sole by-products. ESI/MS and MS/MS
analysis detected all key intermediates and suggest that the
reaction pathway involves decarboxylation of benzoic acid, to
generate the aryl palladium species, followed by addition to
the nitrile. This procedure is one of the simplest and most
convenient methods described for the small-scale synthesis of
A plausible reaction mechanism, exemplified by incorpo-
rating one complex from each category A–D (Scheme 2), and
in agreement with the mechanistic proposals for other related
reactions,[1,9,12] involves the following key steps: 1) coordina-
tion of the carboxylic acid to the palladium(II) center to
generate complex A; 2) decarboxylation of the benzoic acid
to give the aryl–palladium complex B; 3) coordination of the
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[18] a) L. J. Goossen, K. Ghosh, Angew. Chem. 2001, 113, 3566 –
aryl ketones from ortho-substituted benzoic acids. Ongoing
efforts in our laboratory are devoted to expanding the scope
of the reaction and to further investigate the reaction
mechanism by comprehensive DFT calculations.
3568; Angew. Chem. Int. Ed. 2001, 40, 3458 – 3460; b) L. J.
Goossen, K. Ghosh, Eur. J. Org. Chem. 2002, 3254 – 3267; c) R.
Kakino, H. Narahashi, I. Shimizu, A. Yamamoto, Chem. Lett.
2001, 30, 1242 – 1243; d) L. J. Goossen, L. Winkel, A. Dohring,
K. Ghosh, J. Paetzold, Synlett 2002, 1237 – 1240.
Received: May 18, 2010
Revised: July 14, 2010
Published online: September 13, 2010
[19] L. J. Goossen, F. Rudolphi, C. Oppel, N. Rodriguez, Angew.
Chem. 2008, 120, 3085 – 3088; Angew. Chem. Int. Ed. 2008, 47,
3043 – 3045.
[20] a) J. Lindh, P. A. Enquist, ꢁ. Pilotti, P. Nilsson, M. Larhed, J.
Org. Chem. 2007, 72, 7957 – 7962; b) P. A. Enquist, J. Lindh, P.
Nilsson, M. Larhed, Green Chem. 2006, 8, 338 – 343; c) M. M. S.
Andappan, P. Nilsson, M. Larhed, Chem. Commun. 2004, 218 –
219.
[21] a) K. M. Gligorich, M. S. Sigman, Chem. Commun. 2009, 3854 –
3867; b) J. W. Ruan, X. M. Li, O. Saidi, J. L. Xiao, J. Am. Chem.
Soc. 2008, 130, 2424 – 2425; c) J. H. Delcamp, A. P. Brucks, M. C.
White, J. Am. Chem. Soc. 2008, 130, 11270 – 11271; d) J. A.
Schiffer, A. B. Machotta, M. Oestreich, Synlett 2008, 2271 – 2274.
[22] The choice of a monometallic palladium(II)-catalyzed system
might limit the scope of usable benzoic acids to activated ortho-
substituted benzoic acids.
Keywords: carboxylic acids · decarboxylation ·
microwave chemistry · nitriles · palladium
.
[1] a) C. X. Zhou, R. C. Larock, J. Am. Chem. Soc. 2004, 126, 2302 –
2303; b) C. X. Zhou, R. C. Larock, J. Org. Chem. 2006, 71, 3551 –
3558.
[2] a) R. M. Ceder, G. Muller, M. Ordinas, J. I. Ordinas, Dalton
Trans. 2007, 83 – 90; b) B. W. Zhao, X. Y. Lu, Org. Lett. 2006, 8,
5987 – 5990; c) B. W. Zhao, X. Y. Lu, Tetrahedron Lett. 2006, 47,
6765 – 6768; d) K. Ueura, S. Miyamura, T. Satoh, M. Miura, J.
Organomet. Chem. 2006, 691, 2821 – 2826.
[3] S. Darses, J. P. Genet, Chem. Rev. 2008, 108, 288 – 325.
[4] L. J. Goossen, N. Rodriguez, K. Goossen, Angew. Chem. 2008,
120, 3144 – 3164; Angew. Chem. Int. Ed. 2008, 47, 3100 – 3120.
[5] A. F. Shepard, N. R. Winslow, J. R. Johnson, J. Am. Chem. Soc.
1930, 52, 2083 – 2090.
[6] a) M. Nilsson, Acta Chem. Scand. 1966, 20, 423 – 426; b) T.
Cohen, R. A. Schambach, J. Am. Chem. Soc. 1970, 92, 3189 –
3190; c) A. Cairncross, J. R. Roland, R. M. Henderson, W. A.
Sheppard, J. Am. Chem. Soc. 1970, 92, 3187 – 3189.
[7] J. S. Dickstein, C. A. Mulrooney, E. M. OꢀBrien, B. J. Morgan,
M. C. Kozlowski, Org. Lett. 2007, 9, 2441 – 2444.
[8] P. Hu, J. Kan, W. P. Su, M. C. Hong, Org. Lett. 2009, 11, 2341 –
2344.
[9] S. L. Zhang, Y. Fu, R. Shang, Q. X. Guo, L. Liu, J. Am. Chem.
Soc. 2010, 132, 638 – 646.
[10] a) L. J. Goossen, R. T. Werner, N. Rodriguez, C. Linder, B.
Melzer, Adv. Synth. Catal. 2007, 349, 2241 – 2246; b) L. J.
Goossen, C. Linder, N. Rodriguez, P. P. Lange, A. Fromm,
Chem. Commun. 2009, 7173 – 7175.
[11] L. J. Goossen, G. J. Deng, L. M. Levy, Science 2006, 313, 662 –
664.
[12] D. Tanaka, S. P. Romeril, A. G. Myers, J. Am. Chem. Soc. 2005,
127, 10323 – 10333.
[13] a) D. Tanaka, A. G. Myers, Org. Lett. 2004, 6, 433 – 436; b) A. G.
Myers, D. Tanaka, M. R. Mannion, J. Am. Chem. Soc. 2002, 124,
11250 – 11251.
[14] a) L. J. Goossen, B. Zimmermann, T. Knauber, Angew. Chem.
2008, 120, 7211 – 7214; Angew. Chem. Int. Ed. 2008, 47, 7103 –
7106; b) L. J. Goossen, N. Rodriguez, P. P. Lange, C. Linder,
Angew. Chem. 2010, 122, 1129 – 1132; Angew. Chem. Int. Ed.
2010, 49, 1111 – 1114; c) L. J. Goossen, N. Rodriguez, B. Melzer,
C. Linder, G. J. Deng, L. M. Levy, J. Am. Chem. Soc. 2007, 129,
4824 – 4833.
[15] R. Adams, L. O. Binder, J. Am. Chem. Soc. 1941, 63, 2773 – 2776.
[16] C. K. Bradsher, S. T. Webster, J. Am. Chem. Soc. 1957, 79, 393 –
395.
[17] L. S. Liebeskind, J. Srogl, J. Am. Chem. Soc. 2000, 122, 11260 –
11261.
[23] P. Nilsson, K. Olofsson, M. Larhed, Top. Curr. Chem. 2006, 266,
103 – 144.
[24] Recently, a catalytic asymmetric decarboxylative Mannich-type
reaction was reported in which the nucleophile was generated
via CuI-catalyzed decarboxylation of cyanocarboxylic acids. The
reaction occured without detection of any homocoupled product
as a result of carbopalladation of the cyanide substituent, thus
indicating that copper might be
a poor catalyst for our
carboxylic-acid-into-ketone transformation. See: L. Yin, M.
Kanai, M. Shibasaki, J. Am. Chem. Soc. 2009, 131, 9610 – 9611.
[25] The bimetallic reactions were evaluated in a 5 mL Pyrex glass
vial charged with 2-methoxybenzoic acid (0.5 mmol), Pd-
(O2CCF3)2 (0.04 mmol), Cu2O (0.04 mmol) or AgOAc
(0.04 mmol), 6-methyl-2,2’-bipyridine (0.088 mmol), H2O
(200 mL), and MeCN (2 mL). The vial was thereafter capped
under air and exposed to MW heating for 30 min at 1308C.
[26] a) J. E. Bꢂckvall, A. Gogoll, J. Chem. Soc. Chem. Commun.
1987, 1236 – 1238; b) J. Piera, J. E. Bꢂckvall, Angew. Chem. 2008,
120, 3558 – 3576; Angew. Chem. Int. Ed. 2008, 47, 3506 – 3523.
[27] Z. M. Sun, P. J. Zhao, Angew. Chem. 2009, 121, 6854 – 6858;
Angew. Chem. Int. Ed. 2009, 48, 6726 – 6730.
[28] J. B. Culbertson, J. Am. Chem. Soc. 1951, 73, 4818 – 4823.
[29] C. M. Whitehouse, R. N. Dreyer, M. Yamashita, J. B. Fenn, Anal.
Chem. 1985, 57, 675 – 679.
[30] a) L. S. Santos, Eur. J. Org. Chem. 2008, 235 – 253; b) P. A.
Enquist, P. Nilsson, P. J. R. Sjꢃberg, M. Larhed, J. Org. Chem.
2006, 71, 8779 – 8786; c) M. Andaloussi, J. Lindh, J. Sꢂvmarker,
P. J. R. Sjꢃberg, M. Larhed, Chem. Eur. J. 2009, 15, 13069 –
13074; d) J. Lindh, J. Sꢂvmarker, P. Nilsson, P. J. R. Sjꢃberg, M.
Larhed, Chem. Eur. J. 2009, 15, 4630 – 4636; e) A. O. Aliprantis,
J. W. Canary, J. Am. Chem. Soc. 1994, 116, 6985 – 6986; f) J. M.
Brown, K. K. Hii, Angew. Chem. 1996, 108, 679 – 682; Angew.
Chem. Int. Ed. Engl. 1996, 35, 657 – 659; g) A. A. Sabino,
A. H. L. Machado, C. R. D. Correia, M. N. Eberlin, Angew.
Chem. 2004, 116, 2568 – 2572; Angew. Chem. Int. Ed. 2004, 43,
2514 – 2518.
[31] The exact structure of the complexes, that is, the cis/trans
configuration, has not yet been determined.
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