[PdCl2(MeCN)2]-catalyzed highly regio- And stereoselective allylation of electron-rich arenes with 2,3-Allenoates

Article abstract of DOI:10.1002/chem.200903012

Chemical Equation Presented Selective allylation: Several electrondonating arenes such as 1,3,5-trimethoxybenzene, anisole, and phenol underwent palladium-catalyzed selective allylation in TFA/dimethylaceta-mide (DMA) under mild conditions with 2,3-alleno

Full text of DOI:10.1002/chem.200903012

DOI: 10.1002/chem.200903012
ACHTUNGTRENNUNG[PdCl2ACHTUNGTRENNUNG(MeCN)2]-Catalyzed Highly Regio- and Stereoselective Allylation of
Electron-Rich Arenes with 2,3-Allenoates
Zhao Fang, Chunling Fu, and Shengming Ma*[a]
Noticeable progress has been observed in the area of tran-
le.[4g] Hydroarylation of N-(1,2-allenyl)anilines and phenols
affording dihydroquinoline and chromene derivatives were
achieved by Ohno in 2007.[4c] Nelson et al. developed a gold-
catalyzed intramolecular annulation of enantioenriched al-
lenes with pyrrole, which was applied in the total synthesis
of (À)-rhazinilam (Scheme 2).[4b] However, the correspond-
À
sition-metal-catalyzed functionalization of aromatic C H
À
À
À
bonds followed by C C, C O and C N coupling reactions,
which has became one of the most convenient access for the
synthesis of organic intermediates bearing an aryl group.[1]
In addition to these reports, examples have been reported
for the reactions of arenes with unsaturated bonds such as
alkenes,[2] alkynes,[3] and allenes:[4] Fujiwara et al. reported
selective hydroarylation reactions of various electron-rich
arenes with activated alkenes and alkynes including acryla-
tes,[2c,d] propiolates,[2c,d,3] propiolic acids[2c,d] and propiolalde-
hydes[2c,d] at room temperature affording addition products
in which PdACHTUNGTRENNUNG(OAc)2 or PtCl2 served as the catalyst in a
mixed solvent containing trifluoroacetic acid (Scheme 1).
À
À
Scheme 1. Pd-catalyzed addition of aromatic C H bonds to C C unsatu-
rated bonds reported by Fujiwara.
Scheme 2. Previously reported gold(I)-catalyzed intermolecular or intra-
molecular hydroarylations of allenes.
For the reaction with allenes, gold(I)-catalyzed intermo-
lecular or intramolecular hydroarylations of allenes have
been developed.[4] Widenhoefer et al. reported a cyclization
of 3,4-allenoates with an intramolecular indole nucleophi-
ing intermolecular variants are rare except for a recent
result by Gagnꢀ,[4j] in which it was found that unsubstituted
3-methylbuta-1,2-diene worked best with electron-rich
arenes such as 1,3,5-trimethoxybenzene (Scheme 3). We
have been studying the functionalization of electron-rich
arene with allene for long time with very limited success.[5]
In this paper, we wish to report a palladium-catalyzed hy-
droarylation reaction of 2,3-allenoates with high regio-and
stereoselectivity.
[a] Z. Fang, Prof. Dr. C. Fu, Prof. Dr. S. Ma
Department of Chemistry, Zhejiang University
Hangzhou 310027 (PR China)
Fax : (+86)021-62609305
E-mail: masm@mail.sioc.ac.cn
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200903012.
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Chem. Eur. J. 2010, 16, 3910 – 3913

COMMUNICATION
Scheme 3. Gold(I)-catalyzed intermolecular hydroarylation of allenes
with electron-rich arenes.
À
2,3-Allenoates are a class of compounds with two C C
double bonds and one electron-withdrawing group, which
could be inserted into the aryl–Pd species resulting in the
formation of eight types of intermediates depending on the
regio- and stereoselectivity (Scheme 4). As far as we know,
Figure 1. ORTEP Representation of (E)-3a.
À
the insertion of the C C double bonds in allene moiety with
[6]
À
C Pd bond usually led to p-allylic type intermediates,
however, vinylpalladium intermediate with aryl transferred
to the terminal carbon was also observed in some cases.[7]
Thus, control of the regioselectivity and the stereoselectivity
referring to configuration of the remaining double bond is
challenging. Herein we wish to disclose our recent observa-
tion on the Pd-catalyzed high regio- and stereoselective ally-
lation of electron-rich arenes, with the aryl group connecting
at the g position most likely through a vinylpalladium inter-
mediate.
led to a decreased yield (entry 5, Table 1). The reaction in
more acidic trifluoromethanesufonic acid became complicat-
ed probably due to the decomposition of the 2,3-allenoate
2a (entry 6, Table 1). Addition of both metal and non-metal
Lewis acid slightly decreased the yield (compare entries 7
and 8 with entry 4, Table 1). Interestingly, addition of
[PdCl
Thus, the reaction in DMA/TFA (1:4 by volume) with
[PdCl2A(MeCN)2] as the catalyst at 408C is defined as the
2ACHTUNGTRENUN(NG MeCN)2] increased the yield to 64% isolated yield.
CTHUNGTRENNUNG
standard conditions (entry 9, Table 1).
With the optimized reaction conditions in hand, some typ-
ical results of Pd-catalyzed reaction of different buta-2,3-di-
enoates and arene 1a are listed in Table 2. Reactions pro-
ceeded smoothly under the standard conditions affording
differently substituted ethyl 4,4-diarylbut-2(E)-enoate (3) in
moderate to good yields. When 1,3,5-trimethoxybenzene
(1a) was used as the arene, R2 could be methyl, ethyl,
benzyl or allyl group while the yield dropped as the group
became larger probably due to the steric effect (entries 1–4,
Table 2). R1 could be substituted phenyl groups with either
electron-donating groups or electron-withdrawing groups
(entries 5–10, Table 2). As to para-bromo substrate 2j, high
temperature and prolonged reaction time were necessary for
complete conversion of the arene (entry 10, Table 1). Un-
fortunately, when R1 was n-C4H9, no reaction occurred with
recovery of the arene and decomposition of the allenoates
(entry 11, Table 1).
Scheme 4. Different carbopalladation of 2,3-allenoates.
Firstly, we used 1,3,5-trimethoxybenzene (1a) and ethyl 2-
methyl-4-phenylbuta-2,3-dienoate (2a) as the model sub-
strates to screen a series of different conditions. As a first
try, the reaction in a mixture of dichloromethane and TFA
gave the product 3a in 31% yield as the only product indi-
cating the high regio- and stereoselectivity (entry 1,
Table 1). The structure of 3a was unambiguously established
by the X-ray diffraction study indicating the E selectivity of
the double bond and attachment of the aryl group at the g
In addition to 1a, we also tried other types of arenes. To
our delight, the reaction of anisole, a less electron-rich
À
arene, afforded the para C H bond activation based product
ethyl 4,4-diaryl-2-methylbut-2(E)-enoates 3k, 3l, and 3m in
moderate yields exclusively (Scheme 5). Interestingly, even
phenol also underwent this type of highly regioselective
transformation (Scheme 5). This was very different from the
gallium chloride catalyzed hydroarylation of arylacetylene
À
with phenols reported recently in which the otho C H bond
position
G
was functionalized.[9]
result (entry 3, Table 1). It should be noted that addition of
dimethylacetamide (DMA) to TFA as the co-solvent afford-
ed the product in higher yield (entry 4, Table 1). Replace-
ment of TFA in the mixed solvent with trichloroacetic acid
A rationale for this reaction is proposed in Scheme 6. Ac-
tivated PdII species was formed from [PdCl
2ACTHNUTRGNE(UGN MeCN)2] in
TFA[2c,d] which served as an electrophile to proceed electro-
philic palladation reaction generating the aryl-palladium
Chem. Eur. J. 2010, 16, 3910 – 3913
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S. Ma et al.
Table 1. Optimization of reaction conditions for the hydroarylation of 1,3,5-trimethoxybenzene 1a with ethyl
2-methyl-4-phenylbuta-2,3-dienoate 2a.[a]
forms the coordination com-
plex M2. The syn-insertion of
the relatively electron-rich C-C
À
double bond to the s-aryl Pd
bond results in the formation
of intermediate M3. The coor-
dination of carbonyl group
with Pd explains the stereose-
lectivity. Upon protonation
under acidic condition, M3 af-
fords the final product (E)-3
and regenerates the catalytical-
ly active PdII.[2c,d,3]
In conclusion, we have de-
veloped a palladium-catalyzed
highly selective allylation of
1,3,5-trimethoxybenzene, ani-
sole, or phenol in TFA under
mild conditions with 2,3-alle-
noate affording 4,4-diarylbut-
Entry
Solvent
Additive
Recovery of 1a (% by NMR)
NMR yield of 3a [%]
1
2
3
4
5
6
7
8
9
CH2Cl2/TFA
toluene/TFA
TFA
DMA/TFA
DMA/TCA[b]
DMA/TfOH
DMA/TFA
DMA/TFA
DMA/TFA
DMA/TFA
–
–
–
–
–
–
30
47
35
32
36
29
30
27
0
31
29
40
53
34
complex mixture
43
BF3·Et2O[c]
Sc
[PdCl
[Pd(OCOCF3)2]
R
41
A
U
61 (64)[d]
46
10
N
28
[a] The reaction was carried out using 0.3 mmol of 1a, 1.2 equiv of 2a, 5% mmol of additive in 1.2 mL of acid
and 0.3 mL of co-solvent and the yields and recovery were determined by 1H NMR analysis with CH2Br2 as
the internal standard. (TFA=trifluoroacetic acid) [b] The reaction was conducted at 608C because the melting
point of TCA is 57.58C (TCA=trichloroacetic acid). [c] 1.0 equiv of BF3·Et2O was added as the additive.
[d] Isolated yield.
Table 2. Reactions of different 2,3-allenoates with 1,3,5-trimethoxyben-
zene 1a.[a]
Entry
R1
R2
Yield of 3
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Me (2a)
Et (2b)
Bn (2c)
allyl (2d)
Me (2e)
Me (2 f)
Me (2g)
Me (2h)
Me (2i)
Me (2j)
Me (2k)
64 [(E)-3a]
40 [(E)-3b]
50 [(E)-3c]
37 [(E)-3d]
69 [(E)-3e]
61 [(E)-3 f]
38 [(E)-3g]
70 [(E)-3h]
52 [(E)-3i]
51[b] [(E)-3j]
a-naphthyl
p-MeC6H4
p-MeOC6H4
p-FC6H4
p-ClC6H4
p-BrC6H4
n-C4H9
9
10
11
[c]
Scheme 6. Proposed mechanism.
–
[a] The reaction was carried out using 0.3 mmol of 1 and 1.2 equiv of 2 in
0.3 mL of DMA and 1.2 mL of TFA at 408C for 15 h. [b] The reaction
was conducted at 608C for 24 h until 100% conversion of 1a as moni-
tored by TLC. [c] 1a was recovered in 96% NMR yield while 2k decom-
posed under the reaction condition.
2(E)-enoate in moderate yields. Considering the complexity
of this type of products and their potentials as structural
units and building block in organic synthesis, this highly
regio- and stereoselective transformation will be useful in
organic synthesis and medicinal chemistry. Further study on
expansion of the substrate scope and improvement of the
yield was carried out in our laboratory.
Experimental Section
To a reaction tube were added sequentially 1a (49.4 mg, 0.29 mmol),
[PdCl2ACHTNUTRGNEU(GN MeCN)2] (3.5 mg, 0.013 mmol), and DMA (0.3 mL). Then ethyl 2-
Scheme 5. Reactions of different 2,3-allenoates with anisole or phenol.
methyl-4-phenylbuta-2,3-dienoate (2a) (72.9 mg, 0.36 mmol) was added
followed by rinsing with TFA (1.2 mL). After being stirred at 408C for
15 h as monitored by TLC, the resulting mixture was quenched with
10 mL of an aqueous saturated solution of NaHCO3, extracted with di-
ethyl ether (15 mLꢂ3), washed with an aqueous saturated solution of
species M1.[1] Subsequently, coordination of allene moiety
and the ethoxycarbonyl group with the palladium atom
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Highly Regio- and Stereoselective Allylation
COMMUNICATION
NaHCO3, and dried over anhydrous Na2SO4. Filtration, evaporation, and
chromatography on silica gel (petroleum ether/ethyl acetate 7.5:1) afford-
ed (E)-3a (69.6 mg, 64%). White solid; m.p. 90–928C (n-hexane/diethyl
ether); 1H NMR (300 MHz, CDCl3, 208C, TMS): d=7.50 (d, 3J=9.3 Hz,
1H; C=CH), 7.27–7.18 (m, 2H; C=CH), 7.18–7.09 (m, 3H; C=CH), 6.14
(s, 2H; C=CH), 5.59 (d, 3J=9.3 Hz, 1H; CH), 4.18 (q, 3J=7.4 Hz, 2H;
CH2), 3.79 (s, 3H; CH3), 3.71 (s, 6H; CH3), 1.88 (s, 3H; CH3), 1.28 ppm
(t, 3J=7.4 Hz, 3H; CH3); 13C NMR (75 MHz, CDCl3, 208C, TMS) d=
168.6, 160.1, 158.8, 144.1, 143.3, 127.9, 127.4, 127.1, 125.5, 111.3, 91.2,
60.3, 55.7, 55.2, 38.4, 14.3, 12.4 ppm; IR (KBr): n˜ = 3059, 2938, 2838,
1706 (C=O), 1642, 1605, 1493, 1465, 1455, 1418, 1367, 1331, 1280, 1220,
1205, 1151, 1112, 1057, 1037 cmÀ1; MS (70 eV): m/z (%): 370 (10) [M+],
324 (100) [M+ÀOEtÀH]; elemental analysis calcd (%) for C22H26O5: C
71.33, H 7.07; found: C 71.28, H 7.06.
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Acknowledgements
Financial support from the Major State Basic Research and Development
Program (2009CB825300) S. Ma is a Qiu Shi Adjunct Professor at Zhe-
jiang University. We thank Mr. X. Jiang in this group for reproducing the
results presented in entries 4, 7, and 9 in Table 2 and (E)-3n in Scheme 5.
À
Keywords: allenoates · arenes · C H functionalization ·
palladium
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space group P1, final R indices [I>2s(I)], R1=0.0383, wR2=0.1015,
indices (all data) R1=0.0416, wR2=0.1051, a=8.7423(3), b=
R
9.0396(3), c=14.5905(7) ꢄ, a=93.5940(10), b=102.7960(10), g=
116.4640(10)8, V=989.23(7) ꢄ3, T=173 (2) K, Z=2, reflections col-
lected/unique: 11506/3472 (Rint =0.0172), number of observations [I>
2s(I)] 3163, parameters: 244. CCDC-752421 contains the supplemen-
tary crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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Received: October 31, 2009
Published online: March 5, 2010
Chem. Eur. J. 2010, 16, 3910 – 3913
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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