PdCl2-catalyzed two-component cross-coupling cyclization of 2,3-allenoic acids with 2,3-allenols. An efficient synthesis of 4-(1′,3′-dien-2′-yl)-2(5H)-furanone derivatives

Article abstract of DOI:10.1021/ja0500815

Cross-coupling cyclization reaction between 2,3-allenoic acids 1 and 2,3-allenols 2, in which two allenes functioned differently, was realized to afford 4-(1′,3′-dien-2′-yl)-2(5H)-furanone derivatives 3. The reaction may proceed via an oxypalladation, insertion, and β-hydroxide elimination process. A high E-stereoselectivity of the new formed C=C double bond was observed. Copyright

Full text of DOI:10.1021/ja0500815

Published on Web 04/07/2005
PdCl2-Catalyzed Two-Component Cross-Coupling Cyclization of 2,3-Allenoic
Acids with 2,3-Allenols. An Efficient Synthesis of
4-(1′,3′-Dien-2′-yl)-2(5H)-furanone Derivatives
Shengming Ma* and Zhenhua Gu
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 354 Fenglin Lu, Shanghai 200032, P. R. China
Received January 6, 2005; E-mail: masm@mail.sioc.ac.cn
Scheme 1. Cross-Coupling Cyclization Reaction of 1a and 2a
The transition metal-catalyzed coupling cyclization reaction of
functionalized allenes with organic halides has caught the attention
of many synthetic chemists due to the great potential of allenes as
a result of their unique reactivity, axial chirality, and substituent-
loading capability.1,2 Hashmi et al. reported the homodimerization
reaction of 1,2-allenyl ketones.3 We also have shown strong interest
in the reactions involving two allenes by reporting the heterodimer-
ization reaction of 2,3-allenoic acids with 1,2-allenyl ketones4 and
homodimerization of 2,3-allenoic acids.5 It should be noted that in
these two reactions (1) the Pd(II) species was regenerated by
consuming a large amount of 1,2-allenyl ketones via cyclometa-
lation/protonation or an additional oxidant via direct oxidation and
(2) both allenes were cyclized. We wish to report here a coupling
cyclization protocol of two different allenes, in which (1) the
catalytically active Pd(II) species would be regenerated “automati-
cally” after the reaction and (2) two allenes function differently,
that is, 2,3-allenoic acids form the butenolide skeletons while the
2,3-allenols introduce the 1,3-diene substituent to the â-position
of the butenolides formed.
Table 1. PdCl2-Catalyzed Cross-Coupling Reaction of 2,3-Allenoic
Acids and 2,3-Allenolsa
1
2
entry
R1
R2
R3
R4
R5
yield of 3 (%)
1
Me Ph
Me Me
Me Ph
Bn Me
Me (CH2)5 (1d)
Me Ph
H (1a) (CH2)5 (2a)
H (1b) (CH2)5 (2a)
H (1a) Me
67 (3aa)
61 (3ba)
Me (2b) 59 (3ab)
Me (2b) 52 (3cb)
75 (3da)
2
After studying numerous combinations of different allenes,
fortunately we observed that the reaction of 2,3-allenoic acid 1a
with 1.5 equiv of 2,3-allenol 2a in the presence of 5 mol % PdCl2
in 2 mL of DMA afforded 4-(1′,3′-dien-2′-yl)butenolide 3aa in 67%
yield. No cycloisomerization and homodimerization products of 2,3-
allenoic acid 1a were detected (Scheme 1).4
3b
4
H (1c) Me
5
(CH2)5 (2a)
6c
7b
8
H (1a)
H
H (2c)
59 (3ac)
52 (3ea)
62 (3fa)
56 (3ga)
H
n-C7H15
H (1e) (CH2)5 (2a)
H (1f) (CH2)5 (2a)
H (1g) (CH2)5 (2a)
Bn
H
9
Me 1-Nap
Solvents, such as Cl2CHCHCl2 and CH3CN, are not effective
for this reaction. DMA is better than other polar solvents, such as
NMP, DMSO, and DMF (see Supporting Information). Palladium
acetate and PdCl2(PPh3)2 are not effective for the reaction in DMA.
Thus, we have established the proposed protocol for the cross-
coupling cyclization of 2,3-allenoic acid with 2,3-allenol under the
catalysis of 5 mol % PdCl2 in the absence of any oxidant; 2,3-
allenoic acid was cyclized to afford the butenolide skeleton, while
the 2,3-allenol was incorporated into the 4-position of the 2(5H)-
furanone skeleton as a 1,3-dien-2-yl moiety. Some typical results
are listed in Table 1. Various differently substituted 2,3-allenoic
acids that bear an alkyl (entries 2, 5, and 7, Table 1), a benzyl
(entries 4 and 8, Table 1), and an aryl group (entries 1, 3, 6, and
9, Table 1) were successfully cross-coupled with 2,3-allenols to
afford butenolides in moderate yields. The structures of the products
were further established by the X-ray diffraction studies of 3da
(see Supporting Information).
a A solution of 1 (0.25 mmol), 2 (0.375 mmol), and PdCl2 (5 mol %) in
2-3 mL of DMA was stirred at 30 °C for 8-28 h. b A quantity of 0.50
mmol of 2 was used. c A quantity of 0.625 mmol of 2 was used.
occurred smoothly to afford 3aa in 52% yield, indicating that air
does not participate in the catalytic cycle. However, the reaction
did not yield 3aa in the presence of 1.0 equiv of K2CO3, which
indicates the importance of the proton to the catalytic reaction.
In addition, when optically active allenoic acid (R)-(-)-2-methyl-
4-phenyl-2,3-allenoic acid [(R)-(-)-1a] was used as the mechanistic
probe to react with 2b in the presence of 5 mol % PdCl2 in 2 mL
of DMA,4 the product 3ab was formed with partial racemization.
We have observed that a base may induce the racemization of
optically active butenolides.6 Thus, to neutralize any in situ
generated basic species, TFA (CF3COOH) was added to the reaction
mixture, and as a result, the racemization was indeed mostly
inhibited. Best results were obtained with addition of 0.8 equiv of
TFA (Scheme 2). Thus, it was concluded that [OH-] species may
be formed during the reaction, which may induce the partial
racemization of the product.6
Furthermore, it is important to note that with R4 * H and R5 )
H, a very high stereoselectivity was observed affording the products
(E)-3 exclusively (Table 2). The stereochemistry was determined
by the NOESY study of (E)-3dd and the J value of the related
olefinic protons (J ) 15.6 Hz).
On the basis of these experimental findings, it was proposed that
the interaction of PdX2 with (R)-(-)-1a would form 4-furanonyl
palladium intermediate M1 via cyclic oxypalladation, which is
responsible for the high efficiency of chirality transfer observed.4
To clarify the mechanism of this reaction, two controlled
experiments were conducted. Under a N2 atmosphere, the reaction
9
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10.1021/ja0500815 CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
in the absence of TFA.7 Then, XPd+[OH-] was converted to the
catalytically active species, PdX2, by the reaction with H+ (Scheme
3). It should be noted when R4 * H and R5 ) H, the intermediate
M3 was more favored for its thermodynamic stability over M4,
which can easily transform to M3 through a σ-π-σ process.9a
M3 would afford E-isomers highly stereoselectively through a trans-
â-hydroxide elimination (Scheme 4).9
In conclusion, we have established the first coupling cyclization
protocol of two different allenes, that is, 2,3-allenoic acids with
2,3-allenols, affording 4-(1′,3′-dien-2′-yl)-2-furanone derivatives.
On the basis of some brief mechanistic studies, it was concluded
that the reaction may proceed via cyclic oxypalladation, carbopal-
ladation, and â-hydroxide elimination to afford the products by
releasing XPd+[OH-], which may react with H+ to regenerate PdX2.
Further studies in this area are being pursued in our laboratory.
Table 2. Table 2. PdCl2-Catalyzed Stereoselective
Cross-Coupling Reaction of 2,3-Allenoic Acids and 2,3-Allenolsa
1
2
entry
R1
R2
R3
R4
yield of 3 (%)
1b
2
3
4
5
6
7
Me
Me
Me
Me
Me
Me
Me
Me
H (1b)
n-C5H11 (2d)
n-C5H11 (2d)
Ph (2e)
Bn (2f)
Ph (2e)
52 [(E)-3bd]
55 [(E)-3dd]
63 [(E)-3de]
74 [(E)-3df]
66 [(E)-3he]
82 [(E)-3hf]
71 [(E)-3if]
(CH2)5 (1d)
(CH2)5 (1d)
(CH2)5 (1d)
Ph
Ph
Me
Et (1h)
Et (1h)
Me (1i)
Bn (2f)
Bn (2f)
Acknowledgment. Financial support from the Major State Basic
Research Development Program (Grant No. G200077500), National
Nature Science Foundation of China, and Shanghai Municipal
Committee of Science and Technology is greatly appreciated.
a A solution of 1 (0.25 mmol), 2 (0.375 mmol), and PdCl2 (5 mol %) in
2-3 mL of DMA was stirred at 30 °C for 8-28 h. b A quantity of 0.625
mmol of 2 was used.
Scheme 2. Using (R)-(-)-1a as the Mechanistic Probe to React
with 2b
Supporting Information Available: Experimental procedures and
characterization data of all new compounds (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
References
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Scheme 3. Possible Mechanism of the Cross-Coupling
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Scheme 4. A Rationale for the Stereoselectivity Observed
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Then, regioselective carbopalladation of 2,3-allenol 2b with M1
would highly regioselectively form the π-allylic palladium inter-
mediate M2. Subsequent â-hydroxide elimination would afford (R)-
(-)-3ab and XPd+[OH-],7-9 the [OH-] of which may induce the
partial racemization of the product when this reaction was conducted
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