Controlled reactions of 2,3-allenoates with a 1,3-diketone catalyst effect

Article abstract of DOI:10.1002/ejoc.201101852

Two types of reactions of 2,3-allenoates with 1,3-diketones under different reaction conditions are described: under palladium catalysis, the relatively electron-rich C=C bonds are attacked to afford ethyl (2E)-4-acyl-2-alkyl-4-aryl- 6-oxohept-2-enoates exclusively with dicyclohexyl(2,4,6-trimethoxyphenyl) phosphane as the ligand; under Cu(OAc)₂ catalysis, 4-[R-C(=O)-]-(LB-Phos) 3,5-dialkyl-3-(2-oxo-2-arylethyl)furan-2(3H)-one products are formed unexpectedly through intramolecular reaction at the electron-deficient C=C bond.

Full text of DOI:10.1002/ejoc.201101852

FULL PAPER
DOI: 10.1002/ejoc.201101852
Controlled Reactions of 2,3-Allenoates with a 1,3-Diketone Catalyst Effect
Zhao Fang,[a] Chunling Fu,[a] and Shengming Ma*[a]
Keywords: Synthetic methods / C–C coupling / Allenes / Palladium / Copper / Hydroallylation / Ketones
Two types of reactions of 2,3-allenoates with 1,3-diketones
under different reaction conditions are described: under pal-
ladium catalysis, the relatively electron-rich C=C bonds are
attacked to afford ethyl (2E)-4-acyl-2-alkyl-4-aryl-6-oxohept-
2-enoates exclusively with dicyclohexyl(2,4,6-trimethoxy-
phenyl)phosphane as the ligand; under Cu(OAc)2 catalysis,
4-[R–C(=O)–]-(LB-Phos) 3,5-dialkyl-3-(2-oxo-2-arylethyl)-
furan-2(3H)-one products are formed unexpectedly through
intramolecular reaction at the electron-deficient C=C bond.
Introduction
As we know, carbon–carbon bond formation is always a
central topic in organic synthesis.[1] In classic organic syn-
thesis, alkylation of 1,3-dicarbonyl compounds with
organohalides is regarded as one of the most fundamental
ways to construct C–C bonds, although at least a stoichio-
metric amount of base is required and O-alkylation is al-
ways observed.[2] However, the preparation of sophisticated
organic halides is not trivial if a functional group is to be
installed. In addition, there is the issue of regio- and stereo-
selectivity for the allylation.[3] In recent decades, several
groups have focused on the transition-metal-catalyzed reac-
tion of 1,3-dicarbonyl compounds with unsaturated bonds,
including alkenes,[4] alkynes,[5] and 1,3-dienes[6] catalyzed by
various transition-metal catalysts. In most cases, these
transformations proceed highly regioselectively to afford
products in accordance with the Markonikov rule with the
1,3-dicarbonyl moiety connected to the nonterminal posi-
tion (Scheme 1).
Scheme 1. Metal-catalyzed addition reactions of 1,3-dicarbonyls
with alkenes, 1,3-dienes, and terminal alkynes.
However, such reactions for allenes have seldom been re-
ported because of the following challenge:[7] if allenes are
applied to such reactions, products 1–6 may be formed due
to the regio- and stereoselectivity of the remaining C=C
bond (Scheme 2). To make such reactions synthetically at-
tractive, the issues of regio- and stereoselectivity must be
addressed.
On the other hand, electron-deficient allenes may be at-
tacked by nucleophiles: direct conjugate additions of nu-
cleophiles,[8] including activated methylene compounds,[9]
indoles,[10] and Grignard reagents,[11] to electron-deficient
allenes have been established. Herein, we wish to disclose
two distinct reactions initiated by the metal-catalyzed,
Scheme 2. Regio- and stereoselectivity of metal-catalyzed addition
reactions of 1,3-dicarbonyls with allenes.
highly regioselective nucleometallation of each of the two
C=C bonds to form ethyl 5-acyl-2-alkyl-6-oxo-4-arylhept-
2(E)-enoates (3) and 4-[R–C(=O)–]-substituted 3,5-dialkyl-
3-(2-oxo-2-arylethyl)furan-2(3H)-ones (4) under palladium
catalysis with the homemade dicyclohexyl(2,4,6-trimeth-
oxyphenyl)phosphane (LB-Phos) ligand or copper acetate
catalysis, respectively (Scheme 3).
[a] Department of Chemistry, Zhejiang University,
Hangzhou 310027, P. R. China
Fax: +86-021-62609305
E-mail: masm@sioc.ac.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101852.
Eur. J. Org. Chem. 2012, 2585–2596
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Z. Fang, C. Fu, S. Ma
FULL PAPER
Table 1. Optimization of reaction conditions for the hydroallylation
of pentane-2,4-dione (1a) with ethyl 2-methyl-4-phenylbuta-2,3-di-
enoate (2a).[a]
Entry Catalyst
Solvent; T [h]
Yield [%]
E/Z[c]
of 3aa[b]
Scheme 3. Nucleophilic functionalization of 2,3-allenoates.
1
2
3
[PdCl2(PPh3)2]
TFA; 12
48
85:15
78:22
86:14
80:20
62:38
43:57
62:38
81:19
91:9
Ͼ99:1
Ͼ99:1
Ͼ99:1
Ͼ99:1
[PdCl2(PPh3)2]
[PdCl2(PPh3)2]
[PdCl2(PPh3)2]
[PdCl2(PPh3)2]
Pd(OAc)2]
CH3NO2/TFA; 13 54
toluene/TFA; 12 50
CH2Cl2/TFA; 12.5 55
CH2Cl2/TFA; 12
CH2Cl2/TFA; 5
CH2Cl2/TFA; 11
TFA; 15
TFA; 15
TFA; 16
TFA; 16
4
Results and Discussion
5[e]
6
42
35
39
31
43
38
26
The hydroallylation of 2,3-allenoates was tested with
pentan-2,4-dione (1a) and ethyl 2-methyl-4-phenylbuta-2,3-
dienoate (2a). After some trial and error, it was observed
that the reaction in trifluoroacetic acid (TFA) at 30 °C with
[PdCl2(PPh3)2] as the catalyst interestingly afforded ethyl
(2E)-5-acetyl-2-methyl-6-oxo-4-phenylhept-2-enoate [(E)-
3aa] in 41% yield along with its stereoisomer (Z)-3aa in
7% yield (entry 1, Table 1). The structure of (E)-3aa was
unambiguously established by X-ray diffraction, which indi-
cated the position of the connection between the 1,3-di-
carbonyl compound and allene moiety and that the E iso-
mer was the major product (Figure 1).[12] Disappointingly,
when we conducted the reaction in other solvents, a mixture
of stereoisomers was always obtained with poor E/Z selec-
tivities (entries 2–4, Table 1). Mg(ClO4)2, which has a
strong coordination ability, was proposed to activate the
1,3-dicarbonyl compounds by forming a five-membered
ring and led to a decreased yield (entry 5, Table 1). Reac-
tions in CH2Cl2 and TFA in the presence of palladium acet-
ate afforded (E)-3aa in poor yield with poor selectivity (en-
try 6, Table 1). To improve the stereoselectivity, systematic
screening of ligands was conducted: when dppf or dppm
were used, the E/Z selectivity was still not satisfactory (en-
tries 8 and 9, Table 1); the stereoselectivity with dppe or
dppp was high, however, the yields were unacceptable (en-
tries 10 and 11, Table 1). Further ligand screening led to
the observation that when the more bulky and electron-do-
nating ligand LB-Phos, recently developed in our group,[13]
was applied to the reactions, product (E)-3aa was obtained
exclusively in 54% yield (entry 12, Table 1). A palladium
catalyst proved to be necessary because lower yields and
7
8
9
10
11
12
13
–
[PdCl2(dppf)]
[PdCl2(dppm)]
[PdCl2(dppe)]
[PdCl2(dppp)]
[PdCl2(LB-Phos)2] CH2Cl2/TFA; 17
[PdCl2(LB-Phos)2] TFA; 12
54
61(63)[d]
[a] The reaction was carried out by using allenoate 2a (0.3 mmol)
and dione 1a (3.0 equiv.) in cosolvent (0.2 mL) and TFA (0.8 or
1.0 mL); dppf = 1,1Ј-bis(diphenylphosphanyl)ferrocene, dppm =
1,1Ј-bis(diphenylphosphanyl)methane, dppe
= 1,2-bis(diphenyl-
phosphanyl)ethane, dppp = 1,3-bis(diphenylphosphanyl)propane.
[b] The yields were determined by 1H NMR spectroscopic analysis
with CH2Br21as the internal standard. [c] The selectivities were de-
termined by H NMR spectroscopic analysis of the crude product.
[d] Isolated yield. [e] Mg(ClO4)2 (1 equiv.) was added.
Figure 1. ORTEP representation of (E)-3aa. Ellipsoids are drawn
at the 30% probability level.
stereoselectivities were observed in the absence of any cata- ferently substituted products (E)-3 in moderate yields exclu-
lyst (entry 7, Table 1). The best results were obtained for sively. When 1a was used, R4 was a methyl or ethyl group
the reaction in TFA with [PdCl2(LB-Phos)2] as the catalyst (entries 1 and 3, Table 2); R3 was an electron-donating and
at 30 °C, which afforded (E)-3aa in 63% isolated yield (en- -withdrawing group (entries 4 and 5, Table 2). This reaction
try 13, Table 1).
could also be conducted on a larger scale with a similar
With the optimized reaction conditions in hand, hydro- yield and stereoselectivity (entry 2, Table 2). When R1 and
allylation of different 2,3-allenoates with various 1,3-di- R2 were both phenyl groups, allenoates 2 with electron-rich
carbonyl compounds have been performed and the results groups at the R3 position were well tolerated, although a
are summarized in Table 2. The reaction proceeded lower temperature was necessary for a better yield (compare
smoothly under the standard conditions to afford dif- entries 7 and 8, Table 2). Substituted 1,3-diketones or asym-
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Controlled Reactions of 2,3-Allenoates
metric 1,3-diketones could also be applied to this transfor- observed in this transformation. Finally, protonation of M2
mation (entries 9–12, Table 2). Then, the reaction of ethyl afforded the final product (E)-3 and regenerated the catalyt-
2-methyl-4-(α-naphthyl)buta-2,3-dienoate (2e) with 1b was ically active PdII (Scheme 5). The electron-rich and steri-
also tested and gave the corresponding product (E)-3be in cally demanding nature of this monophosphane may ensure
a satisfactory yield (Scheme 4).
the coordination of the carboxyl group:C=C bond and sta-
bilize M1 and M2; thus providing the stereoselectivity and
higher yields.
Table 2. The reaction of different 2,3-allenoates 2 and 1,3-di-
carbonyl compounds 1.[a]
Entry 1/2
R1/R2; R3/R4
T/t
[°C/h]
Yield [%]
1
Me/Me (1a); H/Me (2a)
Me/Me (1a); H/Me (2a)
Me/Me (1a); H/Et (2b)
Me/Me (1a); F/Me (2c)
Me/Me (1a); Me/Me (2d)
C6H5/C6H5 (1b); H/Me (2a)
C6H5/C6H5 (1b); MeO/Me (2f)
C6H5/C6H5 (1b); MeO/Me (2f)
p-MeC6H4/p-MeC6H4 (1c); H/Me (2a)
C6H5/Me (1d); H/Me (2a)
30/12
30/16
40/19
30/10
20/6
63 [(E)-3aa]
58 [(E)-3aa]
45 [(E)-3ab]
50 [(E)-3ac]
65 [(E)-3ad]
2[b]
3
4
5
6
7
8
9
10
30/11.5 64 [(E)-3ba]
0/11
31[c] [(E)-3bf]
–15/11 42 [(E)-3bf]
30/12
30/15
44 [(E)-3ca]
58 (1.13:1)[d]
[(E)-3da]
Scheme 5. Proposed mechanism for the palladium-catalyzed hy-
droallylation reaction.
11
12
C6H5/p-MeC6H4 (1e); H/Me (2a)
C6H5/p-MeOC6H4 (1f); H/Me (2a)
30/12
30/7
54[e] [(E)-3ea]
49[e] [(E)-3fa]
To probe the mechanism, we used [D]TFA as the solvent.
Under the optimized conditions (30 °C), the reaction pro-
ceeded smoothly to afford the expected product [D3]-(E)-
3ba in 67% yield with 88% D incorporation at the D1 posi-
tion (the active methylene carbon atom), 55% D incorpora-
tion at the D2 position (the benzylic carbon atom), and
44% D incorporation at the D3 position (the central carbon
atom of the allene moiety). A control experiment showed
that 0% D incorporation was observed at the D3 position
when (E)-3ba was dissolved in [D]TFA with [PdCl2(LB-
Phos)2] at 30 °C for 11 h and similar D incorporation was
also observed at the other two positions (Scheme 6). These
facts support the mechanism shown in Scheme 5.
[a] The reaction was carried out by using allenoates 2 (0.3 mmol)
and ketones 1 (3.0 equiv.) in TFA (1.0 mL). [b] This reaction was
conducted on a 5 mmol scale. [c] Yield determined by NMR spec-
troscopy. [d] The ratio was determined on the basis of isolated
yield. [e] The product was obtained as a pair of diastereomers that
could not be separated on silica gel or analyzed by 1H NMR spec-
troscopy.
On the other hand, it was exciting for us to note that
when Cu(OAc)2, which is frequently used in the cross-dehy-
drogenation coupling (CDC) reaction of 1,3-dicarbonyl
compounds, was added to the reaction of 1a and 2a in the
mixed solvent of CH3NO2 and TFA (1/4 v/v) at 80 °C with
[PdCl2(PPh3)2], an unexpected product, 4-acetyl-3,5-di-
methyl-3-(2-oxo-2-phenylethyl)furan-2(3H)-one (4aa), was
formed in 22% yield (entry 1, Table 3). The structure was
Scheme 4. Palladium-catalyzed hydroallylation of 1b with 2e.
A rationale for the mechanism of this reaction is depicted unambiguously established by X-ray diffraction and indi-
in Scheme 5.
cationic PdII species formed from cated that it was a five-membered lactone with two different
[PdCl2(LB-Phos)2] in TFA[14] coordinated with the carboxyl ketone functionalities (Figure 2).[15]
A
group and the allene moiety in 2,3-allenoate to generate in-
It is interesting to note that a higher yield was observed
termediate M1. Subsequent exclusive nucleophilic anti-C at- when the palladium catalyst was omitted (entry 2, Table 3).
tack of the enol form of the 1,3-dicarbonyl compounds at A lower temperature led to a poorer yield (entry 3, Table 3),
the 4-position of the palladium-coordinated C=C bond led as did the addition of nitrogen-containing bidentate ligands
to the cyclic vinyl palladium intermediate M2. The configu- (entries 4 and 5, Table 3), Mg(ClO4)2 (entry 6, Table 3), a
ration of the C=C bond in M2 explains the stereochemistry phase-transfer catalyst (entry 7, Table 3), a Lewis acid (en-
Eur. J. Org. Chem. 2012, 2585–2596
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Z. Fang, C. Fu, S. Ma
FULL PAPER
Figure 2. ORTEP representation of 4aa. Ellipsoids are drawn at the
30% probability level.
try 8, Table 3), and an oxidant (entry 9, Table 3). Other co-
solvents were also tested, but gave poorer results (entries
10–12, Table 3). Decreasing the amount of Cu(OAc)2 added
to the reaction also led to a decrease in yield, while increas-
ing the amount of Cu(OAc)2 to 1.2 equiv. also did not lead
to better result (entries 13–15, Table 3).
We then proposed a tentative rationale for the formation
of
4-acetyl-3,5-dimethyl-3-(2-oxo-2-phenylethyl)furan-
Scheme 6. Deuterium-labeling experiment to confirm the predicted
mechanism of the reaction.
2(3H)-one (4). First, transesterification occurred between
the 2,3-allenoate and the enol form of the 1,3-dicarbonyl
compound to form the allenoate intermediate M3
(Scheme 7). Here, in contrast, subsequent attack of the car-
bon center in the enolate at the copper-coordinated rela-
tively electron-deficient C=C bond in the allene moiety af-
forded five-membered intermediate M4. Upon intramolecu-
lar H+ transfer, 4-carbonyl furan-2(3H)-one M5, which has
Table 3. Optimization of reaction conditions for the copper-pro-
moted cyclized hydroalkylation of pentan-2,4-dione (1a) with ethyl
2-methyl-4-phenylbuta-2,3-dienoate (2a).[a]
a
styrene structure, was formed. Finally, attack of
CF3COO– at the C=C bond (a Wacker-type process) af-
forded vinyl trifluoroacetate M6, which was hydrolyzed to
give product 4 (Mechanism A, Scheme 7).[16] For the
Wacker-type transformation from M5 to M6, a PdII catalyst
usually is required. Thus, we prepared compound 5, accord-
ing to a known literature procedure,[17] with a styrene unit
and a neighboring carboxyl group as a mimic of M5. How-
ever, no desired ketone product 6 was formed under the
Entry
Solvent
Additive
Yield [%] of
4aa
1[b]
2
CH3NO2/TFA
CH3NO2/TFA
CH3NO2/TFA
CH3NO2/TFA
CH3NO2/TFA
CH3NO2/TFA
CH3NO2/TFA
CH3NO2/TFA
CH3NO2/TFA
DMA/TFA
hexane/TFA
NMP/TFA
CH3NO2/TFA
CH3NO2/TFA
CH3NO2/TFA
[PdCl2(PPh3)2]
22
–
–
43 (41)[c]
35
3[d]
4
1,10-phenanthroline 24
5
6
Bipy
Mg(ClO4)2
nBu4NI
BF3·Et2O
BQ
–
–
–
–
24
32
32
27
–
–
–
–
7[e]
8[e]
9[f]
10
11
12
13[g]
14[h]
15[i]
41 (43)
39
27
–
–
[a] The reaction was carried out by using allenoate 2a (0.3 mmol)
and 1a (3.0 equiv.) in TFA (1.2 mL) and CH3NO2 (0.3 mL) with
copper acetate (0.3 mmol) at 80 °C and the yields and selectivities
1
were determined by H NMR spectroscopic analysis with CH2Br2
as the internal standard; Bipy = 2,2Ј-bipyridine, DMA = dimethyl-
acetamide, NMP = N-methyl-2-pyrrolidone, BQ = 1,4-benzoqui-
none. [b] 5 mol-% of [PdCl2(PPh3)2] was added. [c] Isolated yield.
[d] The reaction was conducted at 60 °C. [e] 10 mol-% of additive
was added to the reaction. [f] 20 mol-% of Cu(OAc)2, and 1 equiv.
of BQ were added to the reaction. [g] 1.2 equiv. of Cu(OAc)2. [h]
0.8 equiv. of Cu(OAc)2 was used in this reaction. [i] 0.5 equiv. of
Cu(OAc)2 was used in this reaction.
Scheme 7. Proposed mechanism for the copper-promoted hydro-
alkylation–cyclization reaction.
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Controlled Reactions of 2,3-Allenoates
optimized reaction conditions even when PdCl2 was added,
indicating that such a Wacker-type process was indeed im-
possible (Scheme 8). Thus, we reasoned that the product
may be formed by a copper carbenoid mechanism (Mecha-
nism B, Scheme 7): the styrenic C=C bond in M4 may be
attacked by CF3COO– to form copper carbenoid M5Ј. Sub-
sequent 1,2-H shift and hydrolysis would afford 4.
Scheme 9. Transformation between two kinds of products.
Table 4. Copper acetate promoted hydroalkylation–cyclization of
different 1,3-dicarbonyl compounds 1 and 2,3-allenoates 2.[a]
Scheme 8. Some control reactions on the mechanism. DBU = 1,8-
diazabicyclo[5.4.0]undec-7-ene, LiHMDS = lithium bis(trimethylsi-
lyl)amide.
Entry
1
2
t [h]
Yield [%]
of 4
R1/R2
R3/R4
To gain more insight into the two distinct reactions of
2,3-allenoates 2 and 1,3-diketone 1, we investigated the rela-
tionship between furan 2(3H)-ones 4 and heptenoates 3 in
the presence of a copper catalyst. The isolated Pd-catalyzed
hydroalkylation product (E)-3aa was then stirred under the
optimized reaction conditions with Cu(OAc)2. Indeed,
compound 4aa was formed, albeit in 15% yield, indicating
low efficiency for the formation of 4aa from (E)-3aa. Inter-
estingly, the reaction of (E)-3aa with 1b afforded 4aa in
23% yield and 4ba in 27% yield. These results showed that
(E)-3aa could be transformed into 4aa in an intermolecular
manner through cleavage of the allylic C–C bond and at-
tack of diketones (Scheme 9).[18] Thus, compound (E)-3aa
1
2
3
4
5
6
Me/Me (1a)
Me/Me (1a)
Me/Me (1a)
C6H5/C6H5 (1b)
p-MeC6H4/p-MeC6H4 (1c) H/Me (2a)
C6H5/Me (1d) H/Me (2a)
H/Me (2a)
H/Et (2b)
F/Me (2c)
Cl/Me(2g)
11
11
10.5
10
12
41 (4aa)
43 (4ab)
42 (4ac)
54 (4bg)
46 (4ca)
54 (4da)
11
[a] The reaction was carried out by using allenoate (0.5 mmol) ,
ketone (3.0 equiv.), and copper acetate (1 equiv.) in CH3NO2
(0.5 mL) and TFA (2.0 mL).
Conclusions
It was demonstrated that under different reaction condi-
is not the major intermediate in the copper-catalyzed trans- tions two C=C bonds in 2,3-allenoates could be attacked
formation. by the nucleophile: In the palladium-catalyzed reaction, the
Due to the highly functionalized nature of the furanones, relatively electron-rich C=C bond was attacked, leading to
the substrate scope of the copper-promoted intramolecular product (E)-3 with exclusive E stereoselectivity; this repre-
hydroalkylation reaction has been studied. R1 and R2 could sents the first highly selective palladium-catalyzed hydro-
be alkyl or substituted phenyl groups, while R3 should be H allylation reaction of 2,3-allenoates with 1,3-diketones. In
or electron-withdrawing groups to afford the corresponding the copper-promoted transformation, however, unexpected
furanones products 4 in moderate yields (entries 1–6, products 4 were obtained when the electron-deficient C=C
Table 4). Aryl diketones led to slightly higher yields (entries bond was intramolecularly attacked by the 1,3-dicarbonyl
4 and 5, Table 4). When R1 ϶ R2, a pair of separable iso- compounds; the allenoates served as a 2C component to
mers was obtained (entry 6, Table 4).
form the versatile five-membered ring. When considering
Eur. J. Org. Chem. 2012, 2585–2596
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Z. Fang, C. Fu, S. Ma
FULL PAPER
Ethyl (2E)-5-Acetyl-2-ethyl-6-oxo-4-phenylhept-2-enoate: This com-
pound was prepared according to procedure 1. The reaction of 1a
(93 μL, ρ = 0.974, 90.6 mg, 0.90 mmol), 2b (64.0 mg, 0.30 mmol),
and [PdCl2(LB-Phos)2] (13.4 mg, 0.015 mmol) in TFA (1.0 mL) at
40 °C for 19 h afforded (E)-3ab (42.6 mg, 45%) as an oil (eluent for
chromatography: petroleum ether/ethyl acetate = 10:1). 1H NMR
(300 MHz, CDCl3): δ = 7.30–7.19 (m, 2 H, ArH), 7.19–7.09 (m, 3
H, ArH), 6.60 (d, J = 10.5 Hz, 1 H, =CH), 4.41 (t, J = 11.0 Hz, 1
H, ArCH), 4.25 [d, J = 10.8 Hz, 1 H, (C=O)CH], 4.08 (q, J =
7.1 Hz, 2 H, OCH2), 2.48–2.30 (m, 2 H, =CCH2), 2.15 (s, 3 H,
CH3C=O), 1.85 (s, 3 H, CH3C=O), 1.19 (t, J = 7.1 Hz, 3 H, CH3),
0.90 (t, J = 7.5 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3):
δ = 202.0, 201.8, 167.2, 139.4, 138.9, 135.3, 129.1, 127.8, 127.4,
the reverse reactivities of the two C=C bonds in 2,3-al-
lenoates, the unique role of LB-Phos, and the efficient con-
struction of ethyl (2E)-4-acyl-2-alkyl-6-oxo-4-arylhept-2-en-
oates (3) and 4-carbonyl-3,5-dialkyl-3-(2-oxo-2-arylethyl)-
furan-2(3H)-ones (4), these transformation will be of high
interest. Further studies are being carried out in our labora-
tory.
Experimental Section
General Experimental Methods: 1H and 13C NMR spectra were re-
1
corded with an instrument operated at 300 MHz for H NMR and
74.2, 60.6, 44.5, 30.20, 30.17, 20.4, 14.1, 13.3 ppm. IR (neat): ν =
˜
75 MHz for 13C NMR in CDCl3. Chemical shifts (δ) are given in
parts per million (ppm). Infrared spectra were recorded on an
FTIR spectrometer. Mass spectra were recorded in EI mode.
HRMS spectra were recorded in EI mode. TLC was performed on
precoated glass-backed plates and visualized with UV light (λ =
254 nm). Flash column chromatography was performed on silica
gel.
2978, 2937, 1704, 1644, 1494, 1454, 1420, 1358, 1292, 1225, 1190,
1135, 1098, 1041 cm–1. MS (70 eV, EI): m/z (%) = 316 (0.27) [M+],
298 (44.99) [M+ – H2O], 228 (95.68) [M+ – OEt-CH3CO], 199
(99.03) [M+ – H – COOEt – CH3CO], 185 (100). C19H24O4
(316.40): calcd. C 72.13, H 7.65; found C 71.82, H 7.75.
Ethyl (2E)-5-Acetyl-4-(4-fluorophenyl)-2-methyl-6-oxohept-2-eno-
ate: This compound was prepared according to procedure 1. The
reaction of 1a (93 μL, ρ = 0.974, 90.6 mg, 0.90 mmol), 2c (64.1 mg,
0.30 mmol), and [PdCl2(LB-Phos)2] (13.9 mg, 0.015 mmol) in TFA
(1.0 mL) at 30 °C for 10 h afforded (E)-3ac (46.4 mg, 50%) as an
oil (eluent for chromatography: petroleum ether/ethyl acetate =
7.5:1). 1H NMR (300 MHz, CDCl3): δ = 7.23–7.08 (m, 2 H, ArH),
6.98 (t, J = 8.7 Hz, 2 H, ArH), 6.65 (dd, J1 = 10.2 Hz, J2 = 0.9 Hz,
1 H, =CH), 4.47 (t, J = 11.1 Hz, 1 H, ArCH), 4.25 [d, J = 11.1 Hz,
1 H, (C=O)CH], 4.13 (q, J = 7.2 Hz, 2 H, OCH2), 2.18 (s, 3 H,
=CCH3), 1.92 (s, 6 H, 2ϫCH3C=O), 1.24 (t, J = 7.1 Hz, 3 H, CH3)
ppm. 13C NMR (75 MHz, CDCl3): δ = 201.8, 201.6, 167.5, 161.8
(d, J = 245.3 Hz), 139.1, 134.9 (d, J = 3.6 Hz), 129.5, 129.3 (d, J
= 8.1 Hz), 116.0 (d, J = 20.6 Hz), 74.2, 60.8, 43.8, 30.1, 29.8, 14.1,
Preparation of the 1,3-Diketones 1 and 2,3-Allenoates 2: 1,3-Dike-
tones[19] and 4-aryl-2,3-allenoates[20] were prepared according to
known methods.
Preparation of the (2E)-5,5-Diacyl-2-alkyl-4-arylhex-2-enoates 3
Typical Procedure 1: Preparation of Ethyl (2E)-5-Acetyl-2-methyl-6-
oxo-4-phenylhept-2-enoate (E)-3aa: [PdCl2(LB-Phos)2][13] (13.1 mg,
0.014 mmol), TFA (0.2 mL), and 1a (93 μL, ρ = 0.974, 90.6 mg,
0.90 mmol) were added to a reaction tube. Then 2a (62.4 mg,
0.31 mmol) was added followed by TFA (0.8 mL). After being
stirred at 30 °C for 12 h, while being monitored by TLC, the re-
sulting mixture was quenched with an aqueous saturated solution
of NaHCO3 (10 mL) , extracted with diethyl ether (15 mLϫ3),
washed with an aqueous saturated solution of NaHCO3, and dried
with anhydrous Na2SO4. Filtration, evaporation, and chromatog-
raphy on silica gel afforded (E)-3aa (58.7 mg, 63%) (petroleum
ether/ethyl acetate = 5:1) as a white solid; m.p. 66–68 °C (n-hexane/
diethyl ether). 1H NMR (300 MHz, CDCl3): δ = 7.37–7.27 (m, 2
12.7 ppm. 19F NMR (282 MHz): δ = –114.5 ppm. IR (neat): ν =
˜
2983, 2933, 1704, 1648, 1604, 1510, 1446, 1419, 1359, 1280, 1228,
1190, 1161, 1136, 1099, 1031 cm–1. MS (70 eV, EI): m/z (%) = 320
(0.07) [M+], 302 (44.23) [M+ – H2O], 232 (42.73) [M+ – OEt-
CH3CO], 203 (44.29) [M+ – H – COOEt – CH3CO], 189 (100).
C18H21FO4 (320.36): calcd. C 67.49, H 6.61; found C 67.13, H 6.60.
H, ArH), 7.27–7.16 (m, 3 H, ArH), 6.71 (dd, J1 = 10.5 Hz, J2
=
Ethyl (2E)-5-Acetyl-2-methyl-4-(4-methylphenyl)-6-oxohept-2-eno-
ate: This compound was prepared according to procedure 1. The
reaction of 1a (93 μL, ρ = 0.974, 90.6 mg, 0.90 mmol), 2d (62.9 mg,
0.29 mmol), and [PdCl2(LB-Phos)2] (13.4 mg, 0.015 mmol) in TFA
(1.0 mL) at 20 °C for 6 h afforded (E)-3ad (59.6 mg, 65%) as a
white solid (eluent for chromatography: petroleum ether/ethyl acet-
ate = 7.5:1); m.p. 86–88 °C (n-hexane/diethyl ether). 1H NMR
(300 MHz, CDCl3): δ = 7.09 (s, 4 H, ArH), 6.67 (dd, J1 = 10.5 Hz,
J2 = 1.5 Hz, 1 H, =CH), 4.44 (t, J = 10.8 Hz, 1 H, ArCH), 4.29
[d, J = 11.4 Hz, 1 H, (C=O)CH], 4.12 (q, J = 7.1 Hz, 2 H, OCH2),
2.28 (s, 3 H, CH3C=O), 2.19 (s, 3 H, ArCH3), 1.95 (d, J = 1.5 Hz,
3 H, =CCH3), 1.92 (s, 3 H, CH3C=O), 1.24 (t, J = 7.2 Hz, 3 H,
CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 202.2, 202.0, 167.6,
139.7, 137.2, 135.9, 129.8, 129.0, 127.6, 74.1, 60.7, 44.4, 30.0, 29.9,
1.2 Hz, 1 H, =CH), 4.50 (t, J = 10.8 Hz, 1 H, ArCH), 4.34 [d, J =
11.4 Hz, 1 H, (C=O)CH], 4.14 (q, J = 7.1 Hz, 2 H, OCH2), 2.21
(s, 3 H, CH3C=O), 1.97 (d, J = 1.2 Hz, 3 H, =CCH3), 1.93 (s, 3 H,
CH3C=O), 1.26 (t, J = 7.2 Hz, 3 H, CH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 202.0, 201.8, 167.5, 139.4, 139.0, 129.2,
129.1, 127.7, 127.4, 73.9, 60.7, 44.7, 30.1, 29.8, 14.1, 12.7 ppm. IR
(KBr): ν = 3062, 3029, 2982, 2931, 1704, 1648, 1600, 1494, 1454,
˜
1421, 1358, 1279, 1228, 1190, 1156, 1135, 1093, 1030 cm–1. MS
(70 eV, EI): m/z (%) = 302 (0.28) [M+], 284 (49.99) [M+ – H2O],
214 (45.53) [M+ – OEt-CH3CO], 185 (52.45) [M+ – H – COOEt –
CH3CO], 171 (100). C18H22O4 (302.37): calcd. C 71.50, H 7.33;
found C 71.27, H 7.39.
Preparation of (E)-3aa on a Large Scale: The reaction of 1a
(1.5 mL, ρ = 0.974, 1.461 g, 14.6 mmol), 2a (1.0109 g, 5.0 mmol),
and [PdCl2(LB-Phos)2] (0.2259 g, 0.25 mmol) in TFA (17 mL) at
30 °C for 16 h afforded (E)-3aa (880.0 mg, 58%) as a white solid
(eluent for chromatography: petroleum ether/ethyl acetate = 8:1).
1H NMR (300 MHz, CDCl3): δ = 7.36–7.27 (m, 2 H, ArH), 7.27–
7.13 (m, 3 H, ArH), 6.71 (dd, J1 = 10.7 Hz, J2 = 1.1 Hz, 1 H,
=CH), 4.50 (t, J = 10.8 Hz, 1 H, ArCH), 4.34 [d, J = 11.4 Hz, 1
21.0, 14.1, 12.7 ppm. IR (KBr): ν = 2982, 2927, 1705, 1647, 1513,
˜
1446, 1420, 1358, 1278, 1228, 1186, 1157, 1135, 1112, 1092, 1032
cm–1. MS (70 eV, EI): m/z (%) = 316 (0.10) [M+], 298 (63.05) [M+
–
H2O], 228 (43.69) [M+ – OEt-CH3CO], 199 (47.50) [M+ – H – CO-
OEt – CH3CO], 185 (100). C19H24O4 (316.40): calcd. C 72.13, H
7.65; found C 72.05, H 7.69.
H, (C=O)CH], 4.14 (q, J = 7.2 Hz, 2 H, OCH2), 2.21 (s, 3 H, Ethyl
(2E)-5-Benzoyl-2-methyl-6-oxo-4,6-diphenylhex-2-enoate:
CH3C=O), 1.97 (s, 3 H, =CCH3), 1.93 (s, 3 H, CH3C=O), 1.25 (t,
This compound was prepared according to procedure 1. The reac-
J = 7.2 Hz, 3 H, CH3) ppm.
tion of 1b (202.6 mg, 0.90 mmol), 2a (60.7 mg, 0.30 mmol), and
2590
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 2585–2596

Controlled Reactions of 2,3-Allenoates
[PdCl2(LB-Phos)2] (13.2 mg, 0.015 mmol) in TFA (1.0 mL) at 30 °C
for 11.5 h afforded (E)-3ba (81.7 mg, 64%) as a white solid (eluent
for chromatography: petroleum ether/ethyl acetate = 10:1 for the
first round and petroleum ether/ethyl acetate = 15:1 for the second
round); m.p. 127–129 °C (n-hexane/dichloromethane). 1H NMR
cedure 1. The reaction of 1c (225.4 mg, 0.89 mmol), 2a (61.1 mg,
0.30 mmol), and [PdCl2(LB-Phos)2] (14.2 mg, 0.016 mmol) in TFA
(1.0 mL) at 30 °C for 12 h afforded (E)-3ca (59.5 mg, 44%) as a
white solid (eluent for chromatography: petroleum ether/ethyl acet-
ate = 7.5:1); m.p. 139–141 °C (n-hexane/diethyl ether). 1H NMR
(300 MHz, CDCl3): δ = 8.10–7.91 (m, 2 H, ArH), 7.85–7.68 (m, 2 (300 MHz, CDCl3): δ = 7.89 (d, J = 8.1 Hz, 2 H, ArH), 7.69 (d, J =
H, ArH), 7.62–7.03 (m, 11 H, ArH), 6.92 (d, J = 10.8 Hz, 1 H,
=CH), 5.91 [d, J = 10.5 Hz, 1 H, (C=O)CH], 4.94 (t, J = 10.5 Hz,
1 H, ArCH), 4.04 (q, J = 6.4 Hz, 2 H, OCH2), 1.87 (s, 3 H,
=CCH3), 1.16 (t, J = 6.9 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 193.7, 193.5, 167.5, 140.3, 139.9, 136.6, 136.5, 133.5,
133.3, 129.2, 128.8, 128.70, 128.67, 128.5, 128.4, 128.1, 127.0, 62.3,
7.8 Hz, 2 H, ArH), 7.41–7.02 (m, 9 H, ArH), 6.91 (d, J = 10.8 Hz, 1
H, =CH), 5.85 [d, J = 10.8 Hz, 1 H, (C=O)CH], 4.92 (t, J =
10.4 Hz, 1 H, ArCH), 4.04 (q, J = 6.4 Hz, 2 H, OCH2), 2.37 (s, 3
H, ArCH3), 2.31 (s, 3 H, ArCH3), 1.87 (s, 3 H, =CCH3), 1.17 (t, J
= 7.1 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 193.4,
193.1, 167.6, 144.4, 144.2, 140.6, 140.1, 134.2, 134.1, 129.5, 129.2,
129.0, 128.8, 128.7, 128.6, 128.1, 126.9, 62.2, 60.4, 45.6, 21.6, 21.5,
60.5, 45.7, 14.1, 12.6 ppm. IR (KBr): ν = 3062, 3029, 2981, 2925,
˜
1698, 1667, 1596, 1581, 1494, 1448, 1389, 1367, 1283, 1257, 1234,
1199, 1125, 1095, 1029 cm–1. MS (70 eV, EI): m/z (%) = 426 (0.03)
[M+], 408 (3.47) [M+ – H2O], 247 (9.68) [M+ – H – COOEt-PhCO],
105 (100). C28H26O4 (426.51): calcd. C 78.85, H 6.14; found C
78.69, H 6.12.
14.1, 12.6 ppm. IR (KBr): ν = 3030, 2981, 2926, 1694, 1663, 1606,
˜
1572, 1494, 1453, 1408, 1367, 1284, 1261, 1234, 1181, 1122, 1094,
1034, 1002 cm–1. MS (70 eV, EI): m/z (%) = 455 (0.03) [M+ + 1],
454 (0.05) [M+], 436 (4.59) [M+ – H2O], 261 (6.20) [M+ – H –
COOEt – MeC6H4CO], 119 (100). C30H30O4 (454.56): calcd. C
79.27, H 6.65; found C 79.13, H 6.74.
Ethyl (2E)-5-Benzoyl-2-methyl-4-(α-naphthyl)-6-oxo-6-phenylhex-2-
enoate: This compound was prepared according to procedure 1.
The reaction of 1b (202.7 mg, 0.90 mmol), 2a (75.1 mg, 0.30 mmol),
and [PdCl2(LB-Phos)2] (13.1 mg, 0.015 mmol) in TFA (1.0 mL) at
10 °C for 11 h afforded (E)-3be (88.9 mg, 63%) as a white solid
(eluent for chromatography: petroleum ether/ethyl acetate = 10:1);
m.p. 138–140 °C (n-hexane/diethyl ether). 1H NMR (300 MHz,
CDCl3): δ = 8.32 (d, J = 8.4 Hz, 1 H, ArH), 7.98 (d, J = 7.2 Hz, 2
H, ArH), 7.74 (d, J = 7.8 Hz, 1 H, ArH), 7.70–7.62 (m, 2 H, ArH),
7.62–7.23 (m, 9 H, ArH), 7.18 (t, J = 7.5 Hz, 2 H, ArH), 7.02 (dd,
J1 = 10.2 Hz, J2 = 0.9 Hz, 1 H, =CH), 6.20 [d, J = 9.9 Hz, 1 H,
(C=O)CH], 5.77 (t, J = 10.1 Hz, 1 H, ArCH), 4.11–3.92 (m, 2 H,
OCH2), 1.92 (d, J = 0.9 Hz, 3 H, =CCH3), 1.14 (t, J = 6.9 Hz, 3
H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 194.2, 193.5,
167.5, 141.2, 136.7, 136.6, 136.2, 133.9, 133.5, 133.1, 131.3, 129.0,
128.8, 128.6, 128.3, 128.2, 127.7, 126.4, 125.7, 125.3, 125.1, 123.3,
Ethyl (2E)-5-Benzoyl-2-methyl-6-oxo-4-phenylhept-2-enoate: This
compound was prepared according to procedure 1. The reaction of
1d (244.7 mg, 1.51 mmol), 2a (100.7 mg, 0.50 mmol), and
[PdCl2(LB-Phos)2] (22.3 mg, 0.025 mmol) in TFA (1.5 mL) at 30 °C
for 15 h afforded (E)-3da [49.2 mg (less polar isomer), and 55.8 mg
(more polar isomer), 58%] as a white solid (eluent for chromatog-
raphy: petroleum ether/ethyl acetate = 10:1 for the first round and
CH2Cl2 for the second round).
Less Polar Isomer: White solid; m.p. 88–90 °C (n-hexane/diethyl
ether). 1H NMR (300 MHz, CDCl3): δ = 8.07–7.97 (m, 2 H, ArH),
7.74–7.56 (m, 1 H, ArH), 7.54–7.44 (m, 2 H, ArH), 7.39–7.29 (m,
4 H, ArH), 7.29–7.20 (m, 1 H, ArH), 6.65 (dd, J1 = 10.2 Hz, J2 =
1.2 Hz, 1 H, =CH), 5.16 [d, J = 11.1 Hz, 1 H, (C=O)CH], 4.76 (t,
J = 10.7 Hz, 1 H, ArCH), 4.05 (q, J = 7.1 Hz, 2 H, OCH2), 2.00
(d, J = 1.2 Hz, 3 H, =CCH3), 1.96 (s, 3 H, CH3C=O), 1.17 (t, J =
7.2 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 201.9,
193.7, 167.6, 140.1, 139.1, 136.6, 133.9, 129.14, 129.10, 128.85,
128.82, 128.0, 127.5, 68.4, 60.6, 45.2, 28.6, 14.1, 12.8 ppm. IR
61.2, 60.5, 40.4, 14.1, 12.9 ppm. IR (KBr): ν = 3061, 2981, 1697,
˜
1667, 1596, 1580, 1511, 1448, 1395, 1367, 1320, 1273, 1253, 1211,
1124, 1095, 1028, 1000 cm–1. MS (70 eV, EI): m/z (%) = 458 (4.22)
[M+ – H2O], 297 (16.01) [M+ – H – COOEt-PhCO], 105 (100).
C32H28O4 (476.57): calcd. C 80.65, H 5.92; found C 80.62, H 5.96.
(KBr): ν = 3062, 3029, 2982, 2933, 1710, 1677, 1597, 1581, 1494,
˜
1449, 1389, 1358, 1284, 1230, 1202, 1182, 1127, 1091, 1030 cm–1.
MS (70 eV, EI): m/z (%) = 364 (0.12) [M+], 346 (32.33) [M+ – H2O],
105 (100). C23H24O4 (364.44): calcd. C 75.80, H 6.64; found C
75.67, H 6.63.
Ethyl (2E)-5-Benzoyl-4-(4-methoxyphenyl)-2-methyl-6-oxo-6-phen-
ylhex-2-enoate: This compound was prepared according to pro-
cedure 1. The reaction of 1b (203.0 mg, 0.90 mmol), 2f (68.7 mg,
0.30 mmol), and [PdCl2(LB-Phos)2] (13.3 mg, 0.015 mmol) in TFA
(1.0 mL) at –15 °C for 11 h afforded (E)-3bf (57.3 mg, 42%) as a
white solid (eluent for chromatography: petroleum ether/ethyl acet-
ate = 10:1); m.p. 99–101 °C (n-hexane/diethyl ether). 1H NMR
(300 MHz, CDCl3): δ = 7.99 (d, J = 7.5 Hz, 2 H, ArH), 7.79 (d, J
= 7.5 Hz, 2 H, ArH), 7.62–7.37 (m, 4 H, ArH), 7.37–7.15 (m, 4 H,
ArH), 6.91 (d, J = 10.5 Hz, 1 H, =CH), 6.73 (d, J = 8.4 Hz, 2 H,
ArH), 5.88 [d, J = 10.2 Hz, 1 H, (C=O)CH], 4.90 (t, J = 10.5 Hz,
1 H, ArCH), 4.04 (q, J = 7.0 Hz, 2 H, OCH2), 3.67 (s, 3 H, OCH3),
1.87 (s, 3 H, =CCH3), 1.16 (t, J = 7.1 Hz, 3 H, CH3) ppm. 13C
NMR (75 MHz, CDCl3): δ = 193.8, 193.7, 167.6, 158.5, 140.6,
136.8, 136.7, 133.5, 133.2, 131.9, 129.2, 128.9, 128.8, 128.7, 128.6,
More Polar Isomer: White solid; m.p. 117–119 °C (n-hexane/diethyl
ether). 1H NMR (300 MHz, CDCl3): δ = 7.81–7.73 (m, 2 H, ArH),
7.48–7.40 (m, 1 H, ArH), 7.36–7.26 (m, 2 H, ArH), 7.21–7.06 (m,
4 H, ArH), 7.06–6.98 (m, 1 H, ArH), 6.84 (dd, J1 = 10.8 Hz, J2 =
1.5 Hz, 1 H, =CH), 5.08 [d, J = 10.8 Hz, 1 H, (C=O)CH], 4.69 (t,
J = 10.8 Hz, 1 H, ArCH), 4.09 (q, J = 7.1 Hz, 2 H, OCH2), 2.10
(s, 3 H, CH3C=O), 1.92 (d, J = 1.2 Hz, 3 H, =CCH3), 1.20 (t, J =
7.1 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 201.9,
193.8, 167.6, 139.6, 139.5, 136.6, 133.7, 129.4, 128.8, 128.7, 128.5,
127.9, 127.1, 68.9, 60.8, 44.7, 28.2, 14.2, 12.8 ppm. IR (KBr): ν =
˜
3062, 3029, 2981, 2931, 1711, 1677, 1597, 1580, 1494, 1448, 1389,
1366, 1358, 1274, 1231, 1201, 1182, 1157, 1125, 1095, 1057, 1030,
1002 cm–1. MS (70 eV, EI): m/z (%) = 364 (0.09) [M+], 346 (35.37)
[M+ – H2O], 105 (100). C23H24O4 (364.44): calcd. C 75.80, H 6.64;
found C 75.74, H 6.65.
128.5, 114.2, 62.8, 60.4, 55.1, 44.9, 14.1, 12.6 ppm. IR (KBr): ν =
˜
3062, 2981, 2934, 2837, 1698, 1667, 1609, 1596, 1580, 1512, 1448,
1389, 1367, 1323, 1252, 1199, 1179, 1126, 1110, 1034 cm–1. MS
(70 eV, EI): m/z (%) = 438 (49.49) [M+ – H2O], 277 (43.00) [M+
–
Ethyl (2E)-5-Benzoyl-2-methyl-6-oxo-4-phenyl-6-(p-tolyl)hex-2-eno-
ate: This compound was prepared according to procedure 1. The
reaction of 1e (213.1 mg, 0.89 mmol), 2a (61.4 mg, 0.30 mmol), and
H – COOEt-PhCO], 105 (100). C29H28O5 (456.54): calcd. C 76.30,
H 6.18; found C 76.48, H 6.23.
Ethyl
(2E)-2-Methyl-5-(4-methylbenzoyl)-6-oxo-4-phenyl-6-p-tol- [PdCl2(LB-Phos)2] (14.3 mg, 0.016 mmol) in TFA (1.0 mL) at 30 °C
for 12 h afforded (E)-3ea (a pair of diastereomers; 70.7 mg, 54%)
ylhex-2-enoate: This compound was prepared according to pro-
Eur. J. Org. Chem. 2012, 2585–2596
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2591

Z. Fang, C. Fu, S. Ma
FULL PAPER
as a white solid (eluent for chromatography: petroleum ether/ethyl
CDCl3): δ = 197.2, 192.9, 179.4, 162.4, 135.5, 133.5, 128.6, 128.1,
acetate = 15:1); m.p. 119–121 °C (n-hexane/diethyl ether). 1H NMR
122.8, 46.2, 45.2, 30.6, 23.7, 15.6 ppm. IR (KBr): ν = 3061, 2974,
˜
(300 MHz, CDCl3): δ = 8.03–7.94 (m, 1 H, ArH), 7.94–7.85 (m, 1 2933, 1807, 1684, 1638, 1597, 1581, 1449, 1387, 1370, 1342, 1267,
H, ArH), 7.82–7.74 (m, 1 H, ArH), 7.74–7.65 (m, 1 H, ArH), 7.59– 1253, 1228, 1216, 1182, 1146, 1103, 1026, 1013 cm–1. MS (70 eV,
7.38 (m, 2 H, ArH), 7.37–7.02 (m, 8 H, ArH), 6.92 (d, J = 9.9 Hz, EI): m/z (%) = 272 (5.93) [M+], 105 (100). C16H16O4 (272.30): calcd.
1 H, =CH), 5.95–5.82 [m, 1 H, (C=O)CH], 4.93 (t, J = 10.4 Hz, 1 C 70.57, H 5.92; found C 70.51, H 5.90.
H, ArCH), 4.12–3.96 (m, 2 H, OCH2), 2.37 (s), 2.31 (s, 3 H,
4-Acetyl-3-ethyl-5-methyl-3-(2-oxo-2-phenylethyl)furan-2(3H)-one:
This compound was prepared according to procedure 2. The reac-
ArCH3), 1.87 (s, 3 H, =CCH3), 1.22–1.07 (m, 3 H, CH3) ppm. 13C
NMR (75 MHz, CDCl3): δ = 193.9, 193.7, 193.3, 193.0, 167.6,
tion of 1a (154 μL, ρ = 0.974, 150.0 mg, 1.50 mmol), 2b (108.1 mg,
144.5, 144.3, 140.5, 140.1, 140.0, 136.8, 136.7, 134.3, 134.1, 133.4,
0.50 mmol), and Cu(OAc)2 (91.2 mg, 0.50 mmol) in CH3NO2
133.2, 129.50, 129.46, 129.26, 129.18, 129.12, 128.9, 128.8, 128.70,
(0.5 mL) and TFA (2.0 mL) at 80 °C for 11 h afforded 4ab
128.65, 128.5, 128.4, 128.2, 127.0, 62.4, 62.3, 60.5, 60.4, 45.7, 21.6,
(61.2 mg, 43%) as an oil (eluent for chromatography: petroleum
ether/ethyl acetate = 10:1). 1H NMR (300 MHz, CDCl3): δ = 7.96–
7.78 (m, 2 H, ArH), 7.54 (t, J = 7.4 Hz, 1 H, ArH), 7.41 (t, J =
7.5 Hz, 2 H, ArH), 4.33 (d, J = 18.3 Hz, 1 H, one proton of
O=CCH2), 3.28 (d, J = 18.3 Hz, 1 H, one proton of O=CCH2),
2.52 (s, 3 H, =CCH3), 2.31 (s, 3 H, O=CCH3), 2.23–2.05 (m, 1 H,
one proton of CH2), 1.88–1.67 (m, 1 H, one proton of CH2), 0.75
(t, J = 7.4 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ =
197.2, 193.0, 178.9, 163.0, 135.7, 133.5, 128.6, 128.1, 120.0, 51.5,
21.5, 14.11, 14.09, 12.6 ppm. IR (KBr): ν = 3062, 3030, 2981, 2927,
˜
1696, 1665, 1605, 1494, 1449, 1408, 1367, 1318, 1284, 1234, 1181,
1124, 1095, 1032 cm–1. MS (70 eV, EI): m/z (%) = 422 (4.57) [M+
–
H2O], 247 (10.14) [M+ – H – COOEt – MeC6H4CO], 119 (100).
C29H28O4 (440.54): calcd. C 79.07, H 6.41; found C 78.88, H 6.43.
Ethyl (2E)-5-Benzoyl-6-(4-methoxyphenyl)-2-methyl-6-oxo-4-phen-
ylhex-2-enoate: This compound was prepared according to pro-
cedure 1. The reaction of 1f (223.9 mg, 0.88 mmol), 2a (61.9 mg,
0.30 mmol), and [PdCl2(LB-Phos)2] (13.1 mg, 0.014 mmol) in TFA
(1.0 mL) at 30 °C for 7 h afforded (E)-3fa (a pair of diastereomers;
66.8 mg, 49%) as a white solid (eluent for chromatography: petro-
leum ether/ethyl acetate = 7.5:1); m.p. 107–109 °C (n-hexane/diethyl
ether). 1H NMR (300 MHz, CDCl3): δ = 8.10–7.92 (m, 2 H, ArH),
7.85–7.72 (m, 2 H, ArH), 7.59–7.37 (m, 2 H, ArH), 7.36–7.27 (m,
3 H, ArH), 7.24–7.15 (m, 2 H, ArH), 7.15–7.03 (m, 1 H, ArH),
6.97–6.84 (m, 2 H, ArH), 6.82–6.72 (m, 1 H, =CH), [5.84 (d, J =
10.8 Hz), 5.83 (d, J = 10.8 Hz), 1 H, (C=O)CH], [4.93 (t, J =
10.7 Hz), 4.96 (t, J = 10.5 Hz), 1 H, ArCH], 4.14–3.95 (m, 2 H,
OCH2), [3.83 (s), 3.78 (s, 3 H, ArOCH3), 1.96–1.79 (m, 3 H,
=CCH3), [1.174 (t, J = 7.2 Hz), 1.170 (t, J = 7.2 Hz), 3 H, CH3]
ppm. 13C NMR (75 MHz, CDCl3): δ = 194.0, 193.8, 192.0, 191.8,
167.6, 163.9, 163.6, 140.5, 140.2, 140.0, 136.8, 136.7, 133.4, 133.2,
131.2, 131.0, 129.7, 129.6, 129.1, 129.0, 128.75, 128.68, 128.5,
128.4, 128.1, 127.0, 114.0, 113.7, 62.41, 62.38, 60.5, 60.4, 55.5, 55.4,
45.1, 30.5, 29.6, 15.6, 8.1 ppm. IR (neat): ν = 3062, 2969, 2933,
˜
2879, 1807, 1684, 1636, 1597, 1580, 1449, 1387, 1371, 1300, 1227,
1207, 1182, 1148, 1090, 1023 cm–1. MS (70 eV, EI): m/z (%) = 286
(13.75) [M+], 105 (100). HRMS: calcd. for C17H18O4 (M+):
286.1205; found 286.1204.
4-Acetyl-3-[2-(4-fluorophenyl)-2-oxoethyl]-3,5-dimethylfuran-2(3H)-
one: This compound was prepared according to procedure 2. The
reaction of 1a (154 μL, ρ = 0.974, 150.0 mg, 1.50 mmol), 2c
(108.7 mg, 0.49 mmol), and Cu(OAc)2 (91.9 mg, 0.50 mmol) in
CH3NO2 (0.5 mL) and TFA (2.0 mL) at 80 °C for 10.5 h afforded
4ac (62.1 mg, 42%) as a white solid (eluent for chromatography:
petroleum ether/ethyl acetate = 5:1); m.p. 106–108 °C (n-hexane/
diethyl ether). 1H NMR (300 MHz, CDCl3): δ = 7.94–7.84 (m, 2
H, ArH), 7.13–7.02 (m, 2 H, ArH), 4.31 (d, J = 18.3 Hz, 1 H, one
proton of O=CCH2), 3.26 (d, J = 18.3 Hz, 1 H, one proton of
O=CCH2), 2.49 (s, 3 H, =CCH3), 2.30 (s, 3 H, O=CCH3), 1.47 (s,
3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 195.6, 193.0,
179.3, 165.9 (d, J = 254.0 Hz), 162.4, 132.0 (d, J = 2.9 Hz), 130.8
(d, J = 9.4 Hz), 122.7, 115.7 (d, J = 21.8 Hz), 46.2, 45.0, 30.5, 23.6,
45.7, 45.6, 14.1, 12.6 ppm. IR (KBr): ν = 3062, 2980, 2935, 2841,
˜
1694, 1660, 1600, 1574, 1511, 1448, 1420, 1367, 1318, 1259, 1235,
1201, 1171, 1124, 1095, 1028 cm–1. MS (70 eV, EI): m/z (%) = 456
(1.91) [M+], 438 (63.71) [M+ – H2O], 135 (100). C29H28O5 (456.54):
calcd. C 76.30, H 6.18; found C 76.13, H 6.22.
15.6 ppm. 19F NMR (282 MHz): δ = –104.2 ppm. IR (KBr): ν =
˜
3075, 2975, 2934, 1807, 1682, 1634, 1598, 1508, 1449, 1413, 1387,
1344, 1229, 1159, 1102, 1026 cm–1. MS (70 eV, EI): m/z (%) = 290
(17.77) [M+], 123 (100). C16H15FO4 (290.29): calcd. C 66.20, H
5.21; found C 66.16, H 5.29.
Preparation of the Furan-2(3H)-ones 4
Typical Procedure 2. Preparation of 4-Acetyl-3,5-dimethyl-3-(2-oxo-
2-phenylethyl)furan-2(3H)-one: Cu(OAc)2 (92.1 mg, 0.51 mmol),
4-Benzoyl-3-[2-(4-chlorophenyl)-2-oxoethyl]-3-methyl-5-phenylfuran-
2(3H)-one: This compound was prepared according to procedure
2. The reaction of 1b (202.3 mg, 0.90 mmol), 2g (71.2 mg,
0.30 mmol), and Cu(OAc)2 (55.1 mg, 0.30 mmol) in CH3NO2
(0.3 mL) and TFA (1.2 mL) at 80 °C for 10 h afforded 4bg
(69.8 mg, 54%) as a white solid (eluent for chromatography: petro-
leum ether/ethyl acetate = 15:1); m.p. 137–139 °C (n-hexane/diethyl
CH3NO2 (0.5 mL), and 1a (154 μL,
ρ = 0.974, 150.0 mg,
1.50 mmol) were added to a reaction tube. Then 2a (102.4 mg,
0.51 mmol) was added followed by TFA (2.0 mL). After being
stirred at 80 °C for 11 h, while being monitored by TLC, the re-
sulting mixture was cooled to room temperature and quenched
with an aqueous saturated solution of NaHCO3 (10 mL), extracted
with diethyl ether (15 mLϫ3), washed with an aqueous saturated ether). 1H NMR (300 MHz, CDCl3): δ = 7.89–7.82 (m, 2 H, ArH),
solution of NaHCO3, diluted HCl (5%), and an aqueous saturated
solution of NaCl, and dried with anhydrous Na2SO4. Filtration,
evaporation, and chromatography on silica gel afforded 4aa
(56.6 mg, 41%) as a white solid (eluent for chromatography: petro-
leum ether/ethyl acetate = 5:1 for the first round and petroleum
ether/ethyl acetate = 5:1 for the second round); m.p. 98–100 °C (n-
7.55–7.47 (m, 2 H, ArH), 7.44–7.29 (m, 4 H, ArH), 7.29–7.18 (m,
2 H, ArH), 7.17–7.04 (m, 4 H, ArH), 4.11 (d, J = 18.6 Hz, 1 H,
one proton of O=CCH2), 3.49 (d, J = 18.3 Hz, 1 H, one proton of
O=CCH2), 1.78 (s, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3):
δ = 195.8, 192.8, 179.1, 159.3, 140.0, 137.7, 133.9, 132.4, 130.7,
129.5, 129.2, 129.1, 128.9, 128.0, 127.9, 127.8, 119.3, 48.7, 45.0,
1
hexane/diethyl ether). H NMR (300 MHz, CDCl3): δ = 7.91–7.82
24.6 ppm. IR (KBr): ν = 3063, 2973, 2931, 1808, 1684, 1630, 1592,
˜
(m, 2 H, ArH), 7.59–7.50 (m, 1 H, ArH), 7.47–7.37 (m, 2 H, ArH), 1491, 1448, 1401, 1351, 1266, 1214, 1178, 1125, 1094, 1017 cm–1.
4.36 (d, J = 18.6 Hz, 1 H, one proton of O=CCH2), 3.29 (d, J =
MS (70 eV, EI): m/z (%) = 432 (6.96) [M+(37Cl)], 430 (2.65)
18.3 Hz, 1 H, one proton of O=CCH2), 2.50 (s, 3 H, =CCH3), 2.30
[M+(35Cl)], 105 (100). C26H19ClO4 (430.89): calcd. C 72.47, H 4.44;
(s, 3 H, O=CCH3), 1.49 (s, 3 H, CH3) ppm. 13C NMR (75 MHz, found C 72.34, H 4.40.
2592
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 2585–2596

Controlled Reactions of 2,3-Allenoates
3-Methyl-4-(4-methylbenzoyl)-3-(2-oxo-2-phenylethyl)-5-(p-tolyl)-
furan-2(3H)-one: This compound was prepared according to pro-
cedure 2. The reaction of 1c (225.8 mg, 0.90 mmol), 2a (60.7 mg,
0.30 mmol), and Cu(OAc)2 (54.7 mg, 0.30 mmol) in CH3NO2
(0.3 mL) and TFA (1.2 mL) at 80 °C for 12 h afforded 4ca (58.4 mg,
46 %) as a yellow solid (eluent for chromatography: petroleum
ether/ethyl acetate = 15:1); m.p. 148–150 °C (n-hexane/diethyl
1010 cm–1. MS (70 eV, EI): m/z (%) = 334 (8.90) [M+], 105 (100).
HRMS: calcd. for C21H18O4 (M+): 334.1205; found 334.1197.
Preparation of Ethyl 5-Acetyl-2-methyl-6-oxo-4-phenylhept-2(Z)-en-
oate (Z)-3aa: This compound was prepared according to procedure
2. Pd(OAc)2 (11.5 mg, 0.05 mmol), TFA (0.8 mL) and 1a (0.3 mL,
ρ = 0.974, 292.2 mg, 2.92 mmol) were added to a reaction tube.
Then 2a (203.2 mg, 1.01 mmol) was added followed by TFA
(2.2 mL). After being stirred at 11 °C for 19 h, while being moni-
tored by TLC, the resulting mixture was quenched with an aqueous
saturated solution of NaHCO3 (10 mL), extracted with diethyl
ether (15 mLϫ3), washed with an aqueous saturated solution of
NaHCO3, and dried with anhydrous Na2SO4. Filtration, evapora-
tion, and chromatography on silica gel (petroleum ether/ethyl acet-
ate = 10:1) afforded (E)-3aa (42.0 mg, 14%) and (Z)-3aa (65.4 mg,
22%).
1
ether). H NMR (300 MHz, CDCl3): δ = 7.89 (d, J = 7.2 Hz, 2 H,
ArH), 7.57–7.34 (m, 5 H, ArH), 7.32–7.18 (m, 2 H, ArH), 7.00–
6.84 (m, 4 H, ArH), 4.07 (d, J = 18.6 Hz, 1 H, one proton of
O=CCH2), 3.49 (d, J = 18.3 Hz, 1 H, one proton of O=CCH2),
2.24 (s, 3 H, ArCH3), 2.21 (s, 3 H, ArCH3), 1.76 (s, 3 H, CH3)
ppm. 13C NMR (75 MHz, CDCl3): δ = 196.9, 192.6, 179.5, 158.3,
143.3, 141.0, 135.7, 135.2, 133.5, 129.5, 129.0, 128.8, 128.63,
128.56, 128.0, 125.1, 118.6, 48.9, 45.1, 24.8, 21.44, 21.38 ppm. IR
(KBr): ν = 3033, 2972, 2926, 1806, 1685, 1628, 1604, 1511, 1449,
˜
1
(Z)-3aa: Oil. H NMR (300 MHz, CDCl3): δ = 7.27–7.07 (m, 5 H,
1402, 1350, 1265, 1215, 1183, 1163, 1117, 1100, 1032, 1014 cm–1.
MS (70 eV, EI): m/z (%) = 424 (3.14) [M+], 119 (100). C28H24O4
(424.50): calcd. C 79.22, H 5.70; found C 78.85, H 5.70.
ArH), 5.79 (dd, J1 = 10.7 Hz, J2 = 1.4 Hz, 1 H, =CH), 5.27 (t, J
= 11.1 Hz, 1 H, ArCH), 4.20 (qd, J1 = 7.2 Hz, J2 = 1.2 Hz, 2 H,
OCH2), 4.08 [d, J = 11.4 Hz, 1 H, (C=O)CH], 2.11 (s, 3 H,
CH3C=O), 1.83 (s, 3 H, CH3C=O), 1.78 (d, J = 1.5 Hz, 3 H,
=CCH3), 1.28 (t, J = 7.2 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 202.8, 202.5, 167.1, 140.0, 139.1, 128.9, 128.8, 127.7,
4-Benzoyl-3,5-dimethyl-3-(2-oxo-2-phenylethyl)furan-2(3H)-one and
4-Acetyl-3-methyl-3-(2-oxo-2-phenylethyl)-5-phenylfuran-2(3H)-one:
These compounds were prepared according to procedure 2. The
reaction of 1d (243.1 mg, 1.50 mmol), 2a (106.1 mg, 0.53 mmol),
and Cu(OAc)2 (91.8 mg, 0.50 mmol) in CH3NO2 (0.5 mL) and TFA
(2.0 mL) at 80 °C for 11 h afforded 4da-I (68.6 mg, 39%) and 4da-
II (27.1 mg, 15%; eluent for chromatography: petroleum ether/ethyl
acetate = 10:1 for the first round and petroleum ether/ethyl acetate
= 15:1 for the second round).
127.1, 75.0, 60.5, 44.0, 30.3, 28.5, 20.8, 14.2 ppm. IR (neat): ν =
˜
3030, 2982, 2930, 1702, 1646, 1600, 1494, 1453, 1357, 1261, 1219,
1190, 1155, 1135, 1095, 1026 cm–1. MS (70 eV, EI): m/z (%) = 302
(0.30) [M+], 284 (57.23) [M+ – H2O], 214 (47.33) [M+ – OEt-
CH3CO], 185 (51.57) [M+ – H – COOEt – CH3CO], 171 (100).
C18H22O4 (302.37): calcd. C 71.50, H 7.33; found C 71.66, H 7.35.
4da-I: White solid; m.p. 147–148 °C (n-hexane/diethyl ether). 1H
NMR (300 MHz, CDCl3): δ = 7.97–7.87 (m, 2 H, ArH), 7.61–7.47
(m, 4 H, ArH), 7.47–7.35 (m, 4 H, ArH), 4.20 (d, J = 18.3 Hz, 1
H, one proton of O=CCH2), 3.42 (d, J = 18.3 Hz, 1 H, one proton
of O=CCH2), 1.90 (s, 3 H, =CCH3), 1.66 (s, 3 H, CH3) ppm. 13C
NMR (75 MHz, CDCl3): δ = 197.2, 192.5, 179.4, 161.6, 139.9,
135.6, 133.6, 132.4, 128.61, 128.58, 128.3, 128.1, 121.2, 47.0, 44.9,
Deuterium-Labeling Experiments
Ethyl (2E)-5-Benzoyl-3,4,5-trideuterio-2-methyl-6-oxo-4,6-di-
phenylhex-2-enoate ([D3]-(E)-3ba): Following procedure 1, the reac-
tion of 1b (203.1 mg, 0.91 mmol), 2a (61.4 mg, 0.30 mmol), and
[PdCl2(LB-Phos)2] (13.2 mg, 0.015 mmol) in [D]TFA (99.5% D,
1.0 mL) at 30 °C for 13 h afforded [D3]-(E)-3ba (87.1 mg, 67%) as
a white solid (eluent for chromatography: petroleum ether/ethyl
24.3, 15.6 ppm. IR (KBr): ν = 3061, 2972, 2930, 1809, 1683, 1633,
˜
1
acetate = 10:1). H NMR (300 MHz, CDCl3): δ = 8.09–7.94 (m, 2
1597, 1578, 1449, 1385, 1354, 1235, 1216, 1182, 1112, 1046, 1013
cm–1. MS (70 eV, EI): m/z (%) = 334 (11.12) [M+], 105 (100).
C21H18O4 (334.37): calcd. C 75.43, H 5.43; found C 75.32, H 5.43.
H, ArH), 7.87–7.69 (m, 2 H, ArH), 7.59–7.49 (m, 1 H, ArH), 7.49–
7.37 (m, 3 H, ArH), 7.37–7.25 (m, 4 H), 7.27–7.14 (m, 2 H, ArH),
7.14–7.02 (m, 1 H, ArH), 6.97–6.88 (m, 0.56 H, =CH), 5.97–5.89
[m, 0.12 H, (C=O)CH], 5.00–4.89 (m, 0.45 H, ArCH), 4.14–3.93
(m, 2 H, OCH2), 1.87 (s, 3 H, =CCH3), 1.16 (t, J = 7.1 Hz, 3 H,
CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 193.74, 193.73, 193.5,
167.5, 140.3, 140.2, 139.9, 139.8, 136.7, 136.6, 133.5, 133.3, 129.20,
129.18, 129.10, 129.08, 128.8, 128.70, 128.65, 128.5, 128.4, 128.1,
The structure was unambiguously established by X-ray diffraction
(Figure 3).[21]
127.0, 60.4, 45.6, 45.5, 14.1, 12.6, 12.5 ppm. IR (KBr): ν = 3061,
˜
3027, 2981, 2934, 1694, 1663, 1596, 1580, 1494, 1448, 1389, 1367,
1258, 1181, 1132, 1080, 1026, 1001 cm–1. MS (70 eV, EI): m/z (%)
= 429 (0.94) [D3-M+], 428 (0.98) [D2-M+], 427 (0.69) [D1-M+], 426
(0.32) [M+], 411 (1.61) [D3-M+ – H2O], 410 (8.47) [D2-M+ – H2O],
409 (28.83) [D1-M+ – H2O], 408 (26.02) [M+ – H2O], 204 (100).
Figure 3. ORTEP representation of 4da-I. Ellipsoids are drawn at
the 30% probability level.
4da-II: Yellow oil. 1H NMR (300 MHz, CDCl3): δ = 7.98–7.88 (m,
2 H, ArH), 7.68–7.35 (m, 8 H, ArH), 4.36 (d, J = 18.3 Hz, 1 H,
one proton of O=CCH2), 3.41 (d, J = 18.3 Hz, 1 H, one proton of
O=CCH2), 1.90 (s, 3 H, O=CCH3), 1.64 (s, 3 H, CH3) ppm. 13C
NMR (75 MHz, CDCl3): δ = 197.1, 194.8, 179.1, 162.0, 135.7,
135.5, 131.4, 129.4, 129.1, 128.7, 128.6, 128.1, 123.0, 47.3, 45.4,
29.8, 24.0 ppm. IR (neat): ν = 3061, 2979, 2931, 1809, 1684, 1650,
1597, 1490, 1448, 1369, 1344, 1264, 1214, 1182, 1146, 1126, 1075,
Ethyl (2E)-5-Benzoyl-4,5-dideuterio-2-methyl-6-oxo-4,6-diphenyl-
hex-2-enoate ([D2]-(E)-3ba): [PdCl2(LB-Phos)2] (11.1 mg,
˜
Eur. J. Org. Chem. 2012, 2585–2596
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2593

Z. Fang, C. Fu, S. Ma
0.012 mmol), (E)-3ba (107.9 mg, 0.25 mmol), and [D]TFA (99.5% to room temperature and quenched with an aqueous saturated
FULL PAPER
D, 0.8 mL) were added to a reaction tube. After being stirred at
30 °C for 11 h, the resulting mixture was quenched with an aqueous
saturated solution of NaHCO3 (10 mL), extracted with diethyl
ether (15 mLϫ3), washed with an aqueous saturated solution of
NaHCO3, and dried with anhydrous Na2SO4. Filtration, evapora-
tion, and chromatography on silica gel afforded [D2]-(E)-3ba
(65.1 mg, 60%) as a white solid (petroleum ether/ethyl acetate =
solution of NaHCO3 (10 mL), extracted with diethyl ether
(15 mLϫ3), washed with an aqueous saturated solution of
NaHCO3, diluted HCl (5%), and an aqueous saturated solution
of NaCl, and dried with anhydrous Na2SO4. After filtration and
evaporation, the internal standard CH2Br2 (14 μL) was added to
the crude mixture. 1H NMR spectroscopic analysis of the crude
product indicated that no desired ketone product 6 formed and
7.5:1). 1H NMR (300 MHz, CDCl3): δ = 8.04–7.94 (m, 2 H, ArH), 26% of 5 was recovered.
7.83–7.73 (m, 2 H, ArH), 7.59–7.50 (m, 1 H, ArH), 7.49–7.38 (m,
3 H, ArH), 7.37–7.26 (m, 4 H), 7.24–7.15 (m, 2 H, ArH), 7.14–
7.04 (m, 1 H, ArH), 6.98–6.87 (m, 1 H, =CH), 5.94–5.88 [m, 0.08
H, (C=O)CH], 5.00–4.89 (m, 0.48 H, ArCH), 4.11–3.96 (m, 2 H,
OCH2), 1.87 (d, J = 1.2 Hz, 3 H, =CCH3), 1.16 (t, J = 7.1 Hz, 3
H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 193.7, 193.5,
167.5, 140.3, 140.2, 139.92, 139.87, 136.8, 136.7, 133.5, 133.2,
129.2, 128.8, 128.72, 128.67, 128.5, 128.4, 128.1, 127.0, 60.4, 45.6,
Transformation from (E)-3aa to 4aa: Cu(OAc)2 (54.1 mg,
14.1, 12.6 ppm. IR (KBr): ν = 3061, 3030, 2979, 1695, 1662, 1596,
˜
0.30 mmol) and CH3NO2 (0.3 mL) were added to a reaction tube.
Then (E)-3aa (89.6 mg, 0.30 mmol) was added followed by TFA
(1.2 mL). After being stirred at 80 °C for 7 h, while being moni-
tored by TLC, the resulting mixture was cooled to room tempera-
ture and quenched with an aqueous saturated solution of NaHCO3
(10 mL), extracted with diethyl ether (15 mLϫ3), washed with an
aqueous saturated solution of NaHCO3, diluted HCl (5%), and
an aqueous saturated solution of NaCl, and dried with anhydrous
Na2SO4. After filtration and evaporation, the internal standard
CH2Br2 (14 μL) was added to the crude mixture. 1H NMR spectro-
scopic analysis of the crude product indicated that 4aa formed in
19% yield. Chromatography on silica gel afforded 4aa (12.3 mg,
15%) as a white solid (petroleum ether/ethyl acetate = 7.5:1). 1H
NMR (300 MHz, CDCl3): δ = 7.91–7.82 (m, 2 H, ArH), 7.59–7.50
(m, 1 H, ArH), 7.47–7.37 (m, 2 H, ArH), 4.36 (d, J = 18.6 Hz, 1
H, one proton of O=CCH2), 3.30 (d, J = 18.3 Hz, 1 H, one proton
of O=CCH2), 2.51 (s, 3 H, =CCH3), 2.31 (s, 3 H, O=CCH3), 1.50
(s, 3 H, CH3) ppm.
1580, 1494, 1447, 1367, 1256, 1182, 1129, 1026 cm–1. MS (70 eV,
EI): m/z (%) = 428 (0.56) [D2-M+], 427 (0.46) [D1-M+], 426 (0.25)
[M+], 410 (2.44) [D2-M+ – H2O], 409 (11.95) [D1-M+ – H2O], 408
(35.42) [M+ – H2O], 105 (100).
Reactions to Probe the Mechanism
Reaction of 3-Methyl-3-[(E)-styryl]dihydrofuran-2(3H)-one[17] under
Optimized Conditions: Cu(OAc)2 (54.9 mg, 0.30 mmol) and
CH3NO2 (0.3 mL) were added to a reaction tube. Then 5 (61.5 mg,
0.30 mmol) was added followed by TFA (1.2 mL). After being
stirred at 80 °C for 13 h, while being monitored by TLC, the re-
sulting mixture was cooled to room temperature and quenched
with an aqueous saturated solution of NaHCO3 (10 mL), extracted
with diethyl ether (15 mLϫ3), washed with an aqueous saturated
solution of NaHCO3, diluted HCl (5%), and an aqueous saturated
solution of NaCl, and dried with anhydrous Na2SO4. After fil-
tration and evaporation, the internal standard CH2Br2 (14 μL) was
added to the crude mixture. 1H NMR spectroscopic analysis of the
crude product indicated that no desired ketone product 6 formed
and 36% of 5 was recovered.
Reaction of (E)-3aa and 1b: Cu(OAc)2 (53.6 mg, 0.30 mmol), 1b
(67.2 mg, 0.30 mmol), (E)-3aa (91.1 mg, 0.3 mmol), and CH3NO2
(0.3 mL) were added to a reaction tube. Then TFA (1.2 mL) was
added to the mixture. After being stirred at 80 °C for 6 h, while
being monitored by TLC, the resulting mixture was cooled to room
temperature and quenched with an aqueous saturated solution of
NaHCO3 (10 mL), extracted with diethyl ether (15 mLϫ3),
washed with an aqueous saturated solution of NaHCO3, diluted
HCl (5%), and an aqueous saturated solution of NaCl, and dried
with anhydrous Na2SO4. After filtration and evaporation, the in-
ternal standard CH2Br2 (14 μL) was added to the crude mixture.
Chromatography on silica gel (petroleum ether/ethyl acetate =
7.5:1) afforded 4ba (27.6 mg, 23%) and 4aa (22.3 mg, 27%).
Reaction of 3-Methyl-3-[(E)-styryl]dihydrofuran-2(3H)-one with
PdCl2 under Optimized Conditions: PdCl2 (2.5 mg, 0.014 mmol),
Cu(OAc)2 (53.9 mg, 0.30 mmol), and CH3NO2 (0.3 mL) were
added to a reaction tube. Then 5 (61.4 mg, 0.30 mmol) was added
followed by TFA (1.2 mL). After being stirred at 80 °C for 11 h,
while being monitored by TLC, the resulting mixture was cooled
4ba: Oil. 1H NMR (300 MHz, CDCl3): δ = 7.97–7.83 (m, 2 H,
ArH), 7.58–7.46 (m, 3 H, ArH), 7.46–7.37 (m, 2 H, ArH), 7.37–
7.30 (m, 2 H, ArH), 7.25–7.18 (m, 2 H, ArH), 7.16–7.00 (m, 4 H,
ArH), 4.12 (d, J = 18.3 Hz, 1 H, one proton of O=CCH2), 3.53 (d,
2594
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Eur. J. Org. Chem. 2012, 2585–2596

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J = 18.6 Hz, 1 H, one proton of O=CCH2), 1.80 (s, 3 H, CH3)
ppm.
1
4aa: White solid. H NMR (300 MHz, CDCl3): δ = 7.94–7.84 (m,
2 H, ArH), 7.63–7.49 (m, 1 H, ArH), 7.47–7.37 (m, 2 H, ArH),
4.36 (d, J = 18.6 Hz, 1 H, one proton of O=CCH2), 3.30 (d, J =
18.0 Hz, 1 H, one proton of O=CCH2), 2.51 (s, 3 H, =CCH3), 2.31
(s, 3 H, O=CCH3), 1.50 (s, 3 H, CH3) ppm.
[5]
Supporting Information (see footnote on the first page of this arti-
[6]
[7]
1
cle): H NMR and 13C NMR spectra of all products.
Acknowledgments
Financial support from the National Basic Research Program of
China (2011CB808700) and the National Natural Science Founda-
tion of China (NSFC) (21172192). S. M. is a Qiu Shi Ajunct Pro-
fessor at Zhejiang University. We thank Qiong Yu for reproducing
the results presented in entries 8 and 11 in Table 2 and entry 4 in
Table 4.
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Crystal data for (E)-3aa: C18H22O4, MW = 302.36, monoclinic,
space group P2(1)/c, final R indices [IϾ2σ(I)], R1 = 0.0379,
wR2 = 0.0998, R indices (all data) R1 = 0.0398, wR2 = 0.1015,
a = 8.9732(2) Å, b = 8.4306(2) Å, c = 21.6274(6) Å, α = 90°, β
= 100.8950(10)°, γ = 90°, V = 1606.61(7) Å3, T = 173(2) K, Z
= 4, reflections collected/unique: 17987/2834 (Rint = 0.0192),
number of observations [IϾ2σ(I)] 2662, parameters 199.
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Eur. J. Org. Chem. 2012, 2585–2596
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2595

Z. Fang, C. Fu, S. Ma
FULL PAPER
CCDC-837480 contains the supplementary crystallographic
data for (E)-3aa. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
a) B. Lü, C. Fu, S. Ma, Tetrahedron Lett. 2010, 51, 1284–1286;
b) B. Lü, C. Fu, S. Ma, Chem. Eur. J. 2010, 16, 6434–6437.
a) C. Jia, D. Piao, J. Oyamada, W. Lu, T. Kitamura, Y. Fuji-
wara, Science 2000, 287, 1992–1995; b) C. Jia, T. Kitamura, Y.
Fujiwara, Acc. Chem. Res. 2001, 34, 633–639.
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Brogi, E. Novellino, N. Basilico, S. Parapini, D. Taramelli, G.
Campiani, S. Butini, J. Med. Chem. 2011, 54, 5949–5953.
[18] H. Li, W. Li, W. Liu, Z. He, Z. Li, Angew. Chem. 2011, 123,
3031–3034; Angew. Chem. Int. Ed. 2011, 50, 2975–2978.
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yer, Tetrahedron Lett. 2008, 49, 5766–5769.
[20] a) G. Chen, C. Fu, S. Ma, J. Org. Chem. 2006, 71, 9877–9879;
b) see ref.[11a]; c) B. Chen, Z. Lu, G. Chai, C. Fu, S. Ma, J.
Org. Chem. 2008, 73, 9486–9489; d) B. Lü, C. Fu, S. Ma, Org.
Biomol. Chem. 2010, 8, 274–281.
[21] Crystal data for 4da-I: C21H18O4, MW = 334.35, monoclinic,
space group P21/c, final R indices [IϾ2σ(I)], R1 = 0.0922, wR2
= 0.3214, R indices (all data) R1 = 0.1620, wR2 = 0.3341, a =
6.4162(5) Å, b = 20.5344(13) Å, c = 13.4793(8) Å, α = 90.00°,
β = 94.284(6)°, γ = 90.00°, V = 1771.0(2) Å3, T = 293(2) K,
Z = 4, reflections collected/unique: 9512/3115 (Rint = 0.0494),
number of observations [IϾ2σ(I)] 1344, parameters 229.
CCDC-837479 contains the supplementary crystallographic
data for 4da-I. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif..
[13]
[14]
[15] Crystal data for 4aa: C16H16O4, MW = 272.29, monoclinic,
space group P2(1)/c, final R indices [IϾ2σ(I)], R1 = 0.0418,
wR2 = 0.1180, R indices (all data) R1 = 0.0496, wR2 = 0.1253,
a = 14.8230(5) Å, b = 8.4166(3) Å, c = 11.4447(4) Å, α = 90°,
β = 94.7020(10)°, γ = 90°, V = 1423.03(9) Å3, T = 296(2) K, Z
= 4, reflections collected/unique: 16101/2504 (Rint = 0.0713),
number of observations [IϾ2σ(I)] 2078, parameters 182.
CCDC-837478 contains the supplementary crystallographic
data for 4aa. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[16] For the most recent review on Wacker-type reactions, see: R. I.
McDonald, G. Liu, S. S. Stahl, Chem. Rev. 2011, 111, 2981–
3019.
Received: December 25, 2011
Published Online: March 13, 2012
2596
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 2585–2596