Organic iron for the PdCl2/FeCl3-cocatalyzed coupling cyclization of 2,3-allenoates in the presence of allylic bromides

Article abstract of DOI:10.1002/chem.201002553

New coupling: The interaction of ferric chloride with 2,3-allenoates generates a 2-(5H)-furanonyl iron species, which was observed to readily undergo transmetalation with PdCl₂ to result in coupling with allylic bromides (see scheme). Based on

Full text of DOI:10.1002/chem.201002553

DOI: 10.1002/chem.201002553
Organic Iron for the PdCl2/FeCl3-Cocatalyzed Coupling Cyclization of 2,3-
Allenoates in the Presence of Allylic Bromides
Bo Chen[a] and Shengming Ma*[a, b]
In memory of Professor Xian Huang
À
The construction of carbon carbon bonds is a crucial ele-
ment in organic synthesis.[1] Among the transition-metal-cat-
[2]
À
alyzed C C bond formation reactions, palladium-catalyzed
cross-couplings of organic halides and their equivalents with
organometallic reagents of B (Suzuki), Zn (Negishi), Si
(Hiyama) and Sn (Stille), are
now most widely used in both
academic and industrial synthe-
sis (Scheme 1).[3] Recently, such
a coupling reaction with orga-
nogold compounds have also
Scheme 1. Pd or Ni-catalyzed
cross-coupling reactions.
been realized by the Blum[4]
and Hashmi groups[5] based on
Hammondꢀs observation that
the stable organogold compounds may be generated from
the reaction of 2,3-allenoates with gold(I) complex[6]
(Scheme 2).
On the other hand, iron compounds have recently
emerged as promising catalysts in organic synthesis; they
Scheme 2. Cyclization of 2,3-allenoic acids or 2,3-allenoates affording
substituted butenolides.
have attractive potentials in industry due to their low cost
and low toxicity.[7] As early as 1973 Kochi et al. developed
the first example of iron-catalyzed coupling reactions of
Grignard reagents with alkenyl and aryl halides.[8] Other ex-
amples of iron-catalyzed cross-couplings of alkenyl halides
with organometallic compounds (especially Grignard re-
agents) soon followed.[9] Although many examples on the
iron-catalyzed cross-coupling reactions have been reported,
the coupling reaction involving the transmetalation of the
organo-iron species with palladium is hitherto unknown to
the best of our knowledge. In this paper, we wish to report
an unprecedented example of allylic coupling involving in
situ generated iron species.
Based on our early investigations on the palladium(II)-
catalyzed cyclizations of 2,3-allenoic acids in the presence of
allylic halides,[10] itꢀs highly desirable to realize the cycliza-
tion of 2,3-allenoates in the presence of allyl bromide, since
2,3-allenoic acids are usually prepared from the hydrolysis
of 2,3-allenotes in a mixture of allenoic acids and 2-alkynoic
acids. In some cases, the hydrolysis fails to produce 2,3-alle-
noic acids, affording the 2-alkynoic acids as the only prod-
ucts instead. Before we started to develop such a reaction,
we knew that the expected very low reactivity of normal
[a] B. Chen, Prof. Dr. S. Ma
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences
354 Fenglin Lu, Shanghai 200032 (P. R. China)
Fax : (+86)21-6416-7510
E-mail: masm@sioc.ac.cn
[b] Prof. Dr. S. Ma
Shanghai Key Laboratory of Green Chemistry and Chemical Process
Department of Chemistry, East China Normal University
3663 North Zhongshan Lu, Shanghai 200062 (P. R. China)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002553.
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COMMUNICATION
Table 1. Catalyst and concentration effects on the reaction of 2,3-alle-
noate 1a with allyl bromide 2a.
2,3-allenoates for the formation of 2(5H)-furanonyl palladi-
um intermediate as compared to that of 2,3-allenoic acids
would be a great challenge. Indeed, the in situ formation of
2(5H)-furanonyl metal species from 2,3-allenoates is still
crucial except Hammondꢀs pioneering contribution by ap-
plying a stoichiometric amount of expensive AuACTHNUTRGNEUNG
(PPh3)OTf.[6]
Therefore, Blum et al. cleverly developed the cylization of a
special class of esters, that is, allylic 2,3-allenoates, in which
Entry
FeCl3
[mol%]
c [m]
t [h]
NMR yield
of 3a [%]
NMR yield
of 4a [%]
G
À
the reactive esteric allylic C O bond was cleaved by apply-
1[a,b]
2
5
5
5
5
5
1
3
10
1
1
1
0.4
2
1
1
1
35
18
10
33
12
45
20
11
0
0
4
5
7
4
9
5
4
ing a palladium(0) catalyst to afford p-allyl palladium and
2(5H)-furanonyl Au species, which upon further coupling
formed the allylic lactones (Scheme 2).[4] To our delight,
after trial and error, we found that the b-allylic butenolide
was successfully formed under the catalysis of 5 mol% each
of ferric chloride and palladium chloride, which involves the
transmetalation of in situ generated 2(5H)-furanonyl iron
species from the interaction of the routine 2,3-allenoates
and FeCl3 (Scheme 2).
58
57
50
41
41
53
56
3[c]
4
5
6
7
8
[a] [PdACHTNUGTRENNUNG
[c] [PdACHTNUGTRENNUNG
At first, we tried the palladium(II)-catalyzed cyclization
reaction of ethyl 4-phenyl-2-ethyl-2,3-butandienoate (1a)
and allyl bromide (2a) in the presence of the gold(I) com-
plex used by Hammond, Hashmi, and Blum et al.[4–6] How-
ever, after many screenings, under the best conditions the
expected product 3a was formed in very low yields together
Table 2. Solvent effect on the reaction of 2,3-allenoate 1a with allyl bro-
mide 2a.
Entry
Solvent
t [h]
NMR yield
NMR yield
Recovery
of 3a [%]
of 4a [%]
of 1a [%]
1
2
3
4
5
6
7
8
ClCH2CH2Cl
CCl3CH3
CHCl2CH3
CH2Cl2
CHCl2CH2Cl
THF
toluene
CH3CN
n-hexane
benzene
1,4-dioxane
20
20
20
18
20
20
20
20
20
20
20
50
45
55
58
54
29
41
18
7
4
3
4
4
4
10
4
6
1
2
4
0
0
0
0
0
29
0
32
55
8
9
10
11
42
38
12
[a] The reaction was conducted at 1m of 1a.
with the cycloisomerization product 4a [Eqs. (1) and (2)].
We then switched to FeCl3. First, 1 mmol of allenoate 1a
was treated with 5 equiv of allyl bromide in CH2Cl2 (1 mL)
chloro solvents gave similar results (Table 2, entries 1–5),
while other solvents are less effective (Table 2, entries 6–11).
Thus we chose 1 mmol of 2,3-allenoate and 5 equiv of allyl
bromide with 5 mol% each of FeCl3 and PdCl2 in CH2Cl2
(1 mL) at 408C as the standard conditions. Before we con-
tinued, we also tried the reaction by using 5 mol% of CuCl2
instead of FeCl3 to avoid the mistake made in the iron-cata-
lyzed Buchwald–Hartwig amination.[11] As shown in Equa-
tion (3), the yield for 3a was only 16% by NMR under the
using the PdACHTUNGTRENNUNG(PPh3)2Cl2 as the catalyst (Table 1, entry 1),
though the expected product was not formed; however, we
were pleased to note that the PdCl2-catalyzed reaction af-
forded the expected product 3a in 58% NMR yield, togeth-
er with 4% of the cycloisomerization product 4a (Table 1,
entry 2). With PdACHTUNGTRENNUNG(PhCN)2Cl2, the reaction also smoothly af-
forded the expected product 3a in 57% NMR yield, togeth-
er with 5% of the cycloisomerization product 4a (Table 1,
entry 3). Since the results for PdCl2 and PdACHTNUTRGNE(UNG PhCN)2Cl2 are
almost the same, we chose PdCl2 as the catalyst in further
study. Then, we investigated the effects of the substrate con-
centration and catalyst loading (Table 1, entries 4–8).
Based on the results presented in entry 2 of Table 1, we
subsequently tested the solvent effect on the reaction:
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S. Ma and B. Chen
standard conditions for 35 h. In addition, we also noticed
that FeCl3 from Aldrich with a purity of 99.99% provided
very similar results. All these facts exclude the possibility of
a trace amount of copper or other transition metals in FeCl3
we used as the active catalyst in our current transforma-
tions.
the absence of PdCl2, 5 mol% of the cycloisomerization
product 4a was formed with 5 mol% of FeCl3 [Eq. (5)];
16% of 2(5H)-furanone 4a and 19% of 3-chloro-2(5H)-fur-
anone 5a were formed by applying a stoichiometric amount
of FeCl3 [Eq. (6)]. All these results indicated the in situ for-
With the optimized reaction conditions in hand, we start-
ed to investigate the substrate scope of the reaction
(Table 3). The reaction gave a good scope affording differ-
ently substituted butenolides in moderate to good yields.
The substituents of 2,3-allenoates may be aryl, alkyl, cyclo-
alkyl, or benzyl: R1 could be phenyl or substituted phenyl
with electron-donating groups or electron-withdrawing
groups (Table 3, entries 1–8). When R1 is an alkyl group, a
higher temperature was necessary for the current protocal
(Table 3, entries 9 and 10); R2 could be H or alkyl (Table 3,
entry 11); R3 could be alkyl, benzyl, phenyl. 2-Methylallyl
bromide could also react with 2,3-allenoates affording the
corresponding butenolides 3k and 3l in 53 and 65% yield,
respectively (Table 3, entries 11 and 12). In addition, it
À
should be noted that the C Br bond remains untouched due
to the nature of the catalytic cycle involving palladium(II)
(Table 3, entries 3, 4, and 12).
mation of the 2(5H)-furanonyl iron species, which undergo
transmetalation with PdCl2 forming 2(5H)-furanonyl Pd spe-
cies B while regenerating FeCl3. Carbopalladation of B with
allyl bromide followed by dehalopalladation of intermediate
C afforded product 3a and regenerated the catalytically
active species palladium(II).[10]
Table 3. Reaction of 2,3-allenoates 1 with allylic bromides 2.
In conclusion, we have developed an FeCl3/PdCl2-cocata-
lyzed[12] coupling cyclization of 2,3-allenoates with allylic
bromides. This protocol provides a very concise access to b-
allylic substituted butenolides by the direct use of ethyl 2,3-
allenoates utilizing the cheap FeCl3 as the cocatalyst of
PdCl2. Due to the fact that a variety of different 2,3-alle-
noates[13] is more readily available than 2,3-allenoic acids,
this study has greatly expanded the scope of the reaction re-
ported in reference [10]. In addition, it is the first observa-
tion that in situ generated sp2 carbon iron species may un-
dergo transmetalation process with PdCl2, which will be in-
teresting for the further development of transition-metal-
catalyzed coupling reactions involving organic iron species.
Further research in this area is ongoing in our laboratory.
Entry
R1
R2
R3
R4
t [h]
Yield of 3 [%]
1
2
3
4
5
6
7
8
Ph
Ph
H
H
H
H
H
H
H
H
H
Et (1a)
nPr (1b)
Et (1c)
nPr (1d)
nPr (1e)
nPr (1 f)
nPr (1g)
Bn (1h)
Ph (1i)
H
H
H
H
H
H
H
H
H
H
Me
Me
29
15.5
30
60
27
68
71
27
48
33
67
72
51 (3a)
73 (3b)
59 (3c)
53 (3d)
64 (3e)
60 (3 f)
45 (3g)
65 (3h)
40 (3i)
50 (3j)
53 (3k)
65 (3l)
p-BrC6H4
p-BrC6H4
p-ClC6H4
p-FC6H4
p-MeC6H4
Ph
9[a]
10[a,b]
11
12
Et
-(CH2)5-
Ph (1j)
nPr (1b)
nPr (1d)
Ph
p-BrC6H4
H
H
[a] The reaction was conducted at 608C in 1 mL of DCE. The purity of
FeCl3 used is >97%. [b] Methyl ester was used.
Next, a couple of control experiments were conducted to
unveil the mechanism. It should be noted that no reaction
was observed with PdCl2 as the only catalyst [Eq. (4)]. In
Experimental Section
Typical procedure for the synthesis of 4-allyl-3-ethyl-5-phenyl-2(5H)-fur-
anone (3a): To
a dried Schlenk tube were added FeCl3 (8.1 mg,
0.05 mmol), PdCl2 (8.8 mg, 0.05 mmol), allyl bromide (604.2 mg, 5 mmol),
ethyl 4-phenyl-2-ethyl-2,3-butadienoate (217.3 mg, 1 mmol) and CH2Cl2
(1 mL) sequentially under a nitrogen atmosphere at room temperature.
Then, the resulting mixture was stirred at 408C. When the reaction was
complete, as monitored by TLC, the mixture was diluted with Et2O
(20 mL) and filtrated. The filtrate was concentrated, and mesitylene
1
(35 mL) was added for the crude H NMR analysis. Then evaporation and
column chromatography on silica gel (petroleum ether/ethyl acetate
20:1) afforded 3a (0.117 g, 51%) as
CDCl3): d = 7.45–7.31 (m, 3H), 7.24–7.12 (m, 2H), 5.74–5.52 (m, 2H),
a
liquid. 1H NMR (300 MHz,
756
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Cross-Coupling Cyclization
COMMUNICATION
5.08 (d, J=9.9 Hz, 1H), 5.0 (d, J=17.1 Hz, 1H), 3.13 (dd, J1 =15.3, J2 =
5.7 Hz, 1H), 2.70 (dd, J1 =15.3, J2 =7.5 Hz, 1H), 2.37 (q, J=7.5 Hz, 2H),
Martin, Chem. Lett. 2005, 34, 624; c) A. Correa, O. G. MancheÇo, C.
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1.16 ppm (t, J=7.5 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d
= 174.1,
159.9, 134.6, 132.2, 129.1, 128.8, 126.9, 118.0, 83.5, 30.6, 16.9, 12.9 ppm;
IR (neat): n˜ = 3065, 3033, 2973, 2934, 2878, 1758, 1672, 1638, 1495, 1457,
1376, 1371, 1301, 1257, 1224, 1201, 1158, 1105, 1052, 1009 cmÀ1; MS: m/z
(%): 229 (1.94) [M+H]+, 228 (11.33) [M]+, 199 (6.31) [MÀC2H5]+, 187
(100) [MÀC3H5]+; HRMS: m/z: calcd for C15H16O2: 228.1150, found:
228.1149 [M]+.
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Acknowledgements
Financial support from National Natural Science Foundation of China
(20429201 and 20732005) and State Basic and Research Development
Program (Grant No. 2009CB825300) is greatly appreciated. We thank
Xin Huang from this group for reproducing the results presented in en-
tries 3 and 5 in Table 3.
Keywords: allenes · cross-coupling · cyclization · iron ·
palladium
À
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Received: September 3, 2010
Published online: December 7, 2010
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