Diastereoselective [4 + 1] Cycloaddition of Alkenyl Propargyl Acetates with CO Catalyzed by [RhCl(CO)2]2

Article abstract of DOI:10.1021/jo3009403

A class of alkenyl propargyl acetates, RCH(OAc)C≡CC(CH ₃)=CH₂ (5), are found to undergo [4 + 1] cycloaddition with CO (1 atm) in the presence of [RhCl(CO)₂]₂ in refluxing 1,2-dichloroethane to give cyclopentenones (6) in good yields. It has been demonstrated that, when the R group of 5 is a phenyl group bearing o-electron-withdrawing substituents, up to 10:1 diastereoselectivity and 96% yield can be achieved for the [4 + 1] cycloaddition. This process provides a convenient method to construct highly functionalized cyclopentenones that are useful in organic synthesis.

Full text of DOI:10.1021/jo3009403

Article
pubs.acs.org/joc
Diastereoselective [4 + 1] Cycloaddition of Alkenyl Propargyl
Acetates with CO Catalyzed by [RhCl(CO)2]2
Wei Chen,†,‡ Jia-Hui Tay,‡ Xiao-Qi Yu,*,† and Lin Pu*,‡
†Department of Chemistry, Sichuan University, Chengdu, China 610064
‡Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904-4319, United States
S
* Supporting Information
ABSTRACT: A class of alkenyl propargyl acetates, RCH(OAc)C
CC(CH3)CH2 (5), are found to undergo [4 + 1] cycloaddition with
CO (1 atm) in the presence of [RhCl(CO)2]2 in refluxing 1,2-
dichloroethane to give cyclopentenones (6) in good yields. It has been
demonstrated that, when the R group of 5 is a phenyl group bearing o-
electron-withdrawing substituents, up to 10:1 diastereoselectivity and 96%
yield can be achieved for the [4 + 1] cycloaddition. This process provides a
convenient method to construct highly functionalized cyclopentenones that are useful in organic synthesis.
Scheme 2. Attempted Catalytic Conversion of 3
INTRODUCTION
■
Both chiral and achiral propargylic alcohols can be easily
prepared from the reaction of deprotonated terminal alkynes
with aldehydes or ketones.1 This class of compounds is found
to be versatile precursors to structurally diverse organic
molecules, and their application in organic synthesis has been
extensively studied.2,3 These activities include the currently
highly active field of transition-metal-catalyzed isomerizations
and reactions of propargyl esters.4−10
In recent years, our laboratory has also conducted research
projects in the development of the synthetic application of
functional propargylic alcohols.11−14 An example of the
catalytic Pauson−Khand (PK) cycloaddition of the functional
propargylic alcohols investigated in our laboratory is shown in
Scheme 1.14b In this reaction, the 1,3-diyne-based compound 1
reported conversions from a different enyne susbtrate A (R1 ≠
H) to B catalyzed by [Rh(COD)Cl]2 (Scheme 3).4e,j Earlier,
Scheme 3. Catalytic Cycloadditions of Enynes A with CO
Scheme 1. Catalytic PK Cycloaddition of Diynoate 1
underwent the PK cycloaddition with CO catalyzed by
[RhCl(CO)2]2 to generate the bicyclic cyclopentenone 2 with
good diastereoselectivity. We also attempted a PK cyclo-
addition of an alkenyl propargyl ester 3 in the presence of
[RhCl(CO)2]2 and CO (Scheme 2). This reaction, however,
did not generate the expected PK cycloaddition product.
Instead, an apparent [4 + 1] cycloaddition involving the enyne
unit of 3 and CO took place to give a novel cyclopentenone
product 4 in low yield with 1.2:1 E/Z isomers. The β,γ-double
bond of the ester group did not participate in the cyclization.
While this paper was in preparation, Tang and Fukuyama
Brancour reported the reaction of the terminal alkyne-based
substrate A (R1 = H) in the presence of [RhCl(CO)2]2 and CO
to give the six membered ring products C.4d To improve both
the yield and the diastereoselectivity for the conversion of 3 to
4 in Scheme 2, we have explored the reactions of a number of
Received: May 22, 2012
© XXXX American Chemical Society
A
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Scheme 4. Rh(I)-Catalyzed [4 + 1] Cycloaddition of the Alkyl-Substituted Propargyl Acetates
other enyne substrates by replacing the carboxylate group of 3
with acetate and its R group with various alkyl or aryl groups.
We found that an excellent yield and high diastereoselectivity
could be achieved for this Rh(I)-catalyzed [4 + 1] cyclo-
addition. Herein, these results are reported.
Table 1. Rh(I)-Catalyzed [4 + 1] Cycloaddition of Aryl-
Substituted Propargyl Acetates with CO
a
RESULTS AND DISCUSSION
■
Catalytic [4 + 1] Cycloaddition of Alkyl-Substituted
Propargyl Acetates. We first prepared compound 5a15 by
n
treatment of 2-methyl-but-1-en-3-yne with BuLi, followed by
addition to cyclohexanecarboaldehyde and esterification
(Scheme 4). This compound was then heated with [RhCl-
(CO)2]2 in THF at reflux under 1 atm CO. After 24 h, the [4 +
1] cyclopentenone product 6a was obtained in 66% yield with
1.3:1 E/Z selectivity. Further study found that, when THF was
replaced with 1,2-dichloroethane (DCE) as the reaction
solvent, after 15 h, 6a was obtained in 95% yield with 2.2:1
E/Z selectivity. Thus, using DCE led to excellent yield and
improved diastereoselectivity. Under the same conditions,
compound 5b16 with a primary alkyl substituent at the
propargylic position gave the [4 + 1] product 6b in 92%
yield with 2.4:1 E/Z selectivity. The reaction was also found to
work for substrate 5c17 that has a tertiary propargylic center,
which gave 6c in 50% yield. These results show that the enyne
substrates containing alkyl substituents on the propargylic
carbon can undergo efficient [4 + 1] cycloaddition with CO in
the presence of the Rh(I) catalyst with modest diastereose-
lectivity. Previously, a Pd(0)-catalyzed vicinal double carbon-
ylation of 4-en-2-ynyl carbonates, analogues of 5, was reported
to generate cyclopentenone products that are structurally
related to 6.8b
Catalytic [4 + 1] Cycloaddition of Aryl-Substituted
Propargyl Acetates. We then studied the reaction of the
enyne substrates containing various aryl substituents at the
propargylic position by using the same reaction conditions as
described in Scheme 4 with DCE as the solvent. The results are
summarized in Table 1. As shown in entry 1, compound 5d15
containing a phenyl substituent at the propargylic carbon gave
the [4 + 1] product 6d in 85% yield with 2.0:1 E/Z selectivity.
This result is similar to those obtained with the alkyl-
substituted enynes. When an electron-donating methyl group
is introduced to the p-position of the phenyl ring of 5d, the
diastereoselectivity is reduced to 1:1.1, as shown in the
conversion of 5e to 6e (entry 2). However, when the p-methyl
substituent of 5e is placed at the o-position in 5f, the E/Z
selectivity is significantly improved to 4.9:1, as observed in the
product 6f (entry 3). When the electron-donating p-methyl of
a
Conditions: [RhCl(CO)2]2 (10%), CO (1 atm), DCE, reflux.
B
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5e is replaced with an electron-withdrawing p-Cl in 5g, its
conversion to 6g shows a better E/Z selectivity of 2.9:1 than
both 5d and 5e (entry 4). When two electron-withdrawing Cl’s
are incorporated to the o-positions of the phenyl ring, as in 5h,
its conversion to 6h gives a much improved E/Z selectivity of
5.7:1 (entry 5). When the more strongly electron-withdrawing
NO2 and CF3 are introduced to the p-position of the phenyl
ring, as in 5i and 5k (entries 6 and 8), the E/Z selectivities
(4.0:1 and 4.1:1) are better than those of 5d, 5e, and 5g. When
these strongly electron-withdrawing groups are attached to the
o-position of the phenyl ring, further enhancement of the E/Z
selectivity to 6.3:1 and 7.0:1 is observed in the conversions of 5j
and 5l to the products 6j and 6l, respectively (entries 7 and 9).
These results demonstrate that the stereoselectivity of the
Rh(I)-catalyzed [4 + 1] cycloaddition can be enhanced by
reducing the electron density of the phenyl substituent at the
propargylic carbon and also by placing o-substituents on the
phenyl ring to increase the steric bulkiness adjacent to the
propargylic center.
The transformations of the enyne substrates containing 1-
naphthyl (5m) and 2-naphthyl (5n) on the propargylic carbon
were also studied (entries 10, 11). The 2-naphthyl group of 5m
is equivalent to a phenyl group containing a m- and a p-
substituent, and the conversion of 5m to 6m proceeded with
88% yield with 1.4:1 E/Z selectivity (entry 10). The 1-naphthyl
group of 5n is equivalent to a phenyl group containing an o-
and a m-substituent, and the conversion of 5n to 6n proceeded
with a much higher E/Z selectivity of 6.2:1 in 84% yield (entry
11). Thus, similar to those shown in entries 1−9, an o-
substituent on the phenyl ring increases the stereoselectivity,
but a p- or m-substituent is less favorable.
The reaction of compound 5o with a biphenyl substituent o-
linked to the propargylic carbon gave the product 6o in 82%
yield with a good 7.2:1 E/Z selectivity (entry 12). When two
electron-withdrawing fluorine substituents were introduced, the
resulting substrate 5p showed a further enhanced E/Z
selectivity of 10:1 (entry 13). This is consistent with the
observation that an electron-withdrawing o-substituent on the
phenyl ring at the propargylic position can lead to high E/Z
selectivity for the Rh(I)-catalyzed [4 + 1] cycloaddition of the
alkenyl propargylic esters.
The NOESY spectra of E- and Z-6d have allowed the
determination of their stereochemistry (Supporting Informa-
tion, page S48). NOE effects were observed for E-6d between
the aromatic protons Ha and Hb at δ 7.35 and the AcO proton
signal at δ 1.80. In contrast, no NOE effect between the
aromatic protons and the AcO protons was observed for Z-6d.
The AcO protons in E-6d are also significantly shielded by the
aromatic ring to give a more upfield-shifted signal than those in
Z-6d. The E/Z isomers of the other reaction products were
determined by comparison of their NMR spectra with those of
E- and Z-6d.
been studied extensively.4−10 On the basis of these previous
reports, a mechanism for the Rh(I)-catalyzed [4 + 1]
cycloaddition can be proposed in Scheme 5. Coordination of
the triple bond of the substrate 6 to the Rh(I) center could
generate the intermediate 7. 1,3-Acetate migration of 7 could
generate the allene intermediate 8a and 8b.4 It is expected that
the o-substituted phenyl ring of 8a should have increased the
steric interaction with the ligands on the Rh, which makes 8b
more favorable than 8a. Previously, Murakami had reported a
Rh catalyzed reaction of isolated vinyl allenes with CO that
gave similar [4 + 1] cycloaddition products.18 According to
their mechanistic study, the η4 complexes 8a and 8b could
undergo oxidative coupling to generate the metallacyclopentene
intermediates 9a and 9b, respectively. In 9b, an electron-
deficient benzene ring could have a favorable π−π attraction
with the π electrons of the acetate group. This π−π interaction
is supported by the significantly shielded AcO proton signal of
E-6d in its 1H NMR spectrum. Therefore, an o-electron-
withdrawing substituent on the phenyl ring would favor the
formation of the intermediate 9b. Complexes 9a and 9b can
then undergo CO insertion and reductive elimination to
generate the Z and E products 6, respectively. Thus, the o-
electron-withdrawing group on the phenyl ring of the substrate
would lead to the formation of E-6 as the major product via the
formation of the sterically and electronically more favorable
intermediates 8b and 9b.
Catalytic [4 + 1] Cycloaddition of the Substrates
Containing a Vinyl Group on the Propargylic Carbon.
We also investigated the Rh(I)-catalyzed [4 + 1] cycloaddition
of the constitutional isomers of the enyne substrates 5, such as
10a and 10b, similar to A (R ≠ H) in Scheme 3, in which the
vinyl groups are on the propargylic carbon rather than on the
alkyne carbon (Scheme 6). It was found that both 10a and 10b
were converted to the cyclopentenone products 11a and 11b
with good Z/E selectivities of 7.0:1 and 5.7:1, respectively, in
the presence of [RhCl(CO)2]2 and CO. The stereochemistry of
Z-11a was determined by observing the NOE effect between its
aromatic protons and the vinyl proton on the cyclopentenone
ring in its 2D NOESY spectrum (see the Supporting
Information, page S49). Unlike those in products 6, the acetate
groups in 11a and 11b are not on the cyclopentenone ring. The
mechanism proposed for the conversion of 5 to 6 in Scheme 5
could also be applied to illustrate the conversion of 10 to 11.
That is, the Rh(I)-promoted 1,3-migration of the acetate group
of the Rh(I)−alkyne complex 12, followed by cyclization,
should give an intermediate like 13. The coordination of the
acetate group to the Rh(I) center in 13 and the subsequent CO
insertion and reductive elimination can explain the stereo-
selective formation of the products Z-11. These results
resemble those reported by Tang and Fukuyama.4e,j
Summary. In summary, we have discovered a Rh(I)-
catalyzed [4 + 1] cycloaddition of vinyl propargyl acetates with
CO to generate cyclopentenone products. In this reaction, it
has been demonstrated that good diastereoselectivity can be
achieved for the enyne substrates bearing an aromatic ring at
the propargylic carbon with electron-withdrawing or o-
substituents. The stereoelectronic effects of the substrates on
the diastereoselectivity can be rationalized by a mechanism
involving the Rh(I)-promoted 1,3-acetate migration, followed
by the [4 + 1] cycloaddition of the Rh(I)-coordinated vinyl
allene intermediates with CO. Because of the easily available
starting material and the mild reaction conditions, this work
Mechanistic Illustration of the Stereoselectivity.
Transition-metal-catalyzed isomerization of propargylic esters
and the subsequent inter- or intramolecular conversions have
C
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Scheme 5. Proposed Mechanism for the Rh(I)-Catalyzed [4 + 1] Cycloaddition
Scheme 6. Rh(I)-Catalyzed [4 + 1] Cycloaddition of Compounds 10
Hz), 3.10 (t, 1H, J = 1.4 Hz), 3.08 (t, 1H, J = 1.4 Hz), 1.84 (s, 3H),
1.74 (m, 2H), 1.38 (m, 2H), 1.26 (m, 8H), 0.85 (t, 3H, J = 6.6 Hz).
13C NMR (75 MHz, CDCl3): δ 170.6, 130.2, 126.2, 122.8, 118.8, 86.6,
85.7, 64.9, 39.3, 35.0, 31.9, 29.3, 29.2, 25.2, 23.5, 22.8, 14.3. Colorless
oil. HRMS (EI) for C17H26O2 (M) Calcd: 262.1933. Found: 262.1931.
Cyclohexyl-4-methylpent-4-en-2-yn-1-yl Acetate, 5a:15 161 mg,
provides a convenient method to construct functional cyclo-
pentenones that are useful in organic synthesis.
EXPERIMENTAL SECTION
■
General Procedure for the Preparation of Alkenyl Prop-
argylic Esters 3, 5, and 10. Under nitrogen, an alkyne (1.6 equiv)
was dissolved in THF (5.0 mL) and cooled to −78 °C. BuLi (1.4
1
73% yield. H NMR (300 MHz, CDCl3): δ 5.28 (m, 2H), 5.20 (m,
n
1H), 2.04 (s, 3H), 1.84 (m, 3H), 1.71 (m, 6H), 1.13 (m, 5H). 13C
NMR (75 MHz, CDCl3): δ 170.2, 126.3, 122.7, 87.2, 84.8, 68.8, 42.1,
28.8, 28.3, 26.4, 26.0, 25.9, 23.5, 21.2.
equiv) was added, and the mixture was stirred for 30 min. An aldehyde
(1.0 mmol) was then added. After 1 h, the reaction was quenched with
saturated aqueous ammonium chloride and extracted three times with
CH2Cl2. The organic layer was dried with sodium sulfate and
concentrated by rotary evaporation. The resultant oil was purified by
flash column chromatography on silica gel eluted with hexanes/ethyl
acetate to afford the product in 50−95% yield. The product was then
dissolved in CH2Cl2 (0.5 M), and Ac2O (2 equiv), pyridine (4 equiv)
[4-pentenoic acid (2 equiv) and DCC (2 equiv) were added instead to
prepare ester 3], and DMAP (0.1 equiv) were added. After the reaction
was determined to be complete by TLC, it was quenched with
saturated aqueous ammonium chloride and extracted three times with
CH2Cl2. The organic layer was dried with sodium sulfate and
concentrated by rotary evaporation. The resultant oil was purified by
flash column chromatography on silica gel eluted with hexanes/ethyl
acetate to afford the product in 90−99% yield.
6-Methylhept-6-en-4-yn-3-yl Acetate, 5b:16 136 mg, 82% yield. 1H
NMR (300 MHz, CDCl3): δ 5.43 (t, 1H, J = 6.6 Hz), 5.30 (s, 1H),
5.23 (m, 1H), 2.08 (s, 3H), 1.87 (s, 3H), 1.79 (m, 2H), 1.00 (t, 3H, J =
7.5 Hz). 13C NMR (75 MHz, CDCl3): δ 170.2, 126.3, 122.9, 86.7,
85.5, 65.8, 28.4, 23.5, 21.3, 9.6.
1-(3-Methylbut-3-en-1-yn-1-yl)cyclohexyl Acetate, 5c:17 93 mg,
1
45% yield. H NMR (300 MHz, CDCl3): δ 5.26 (s, 1H), 5.18 (m,
1H), 2.10 (m, 2H), 2.01 (s, 3H), 1.86 (s, 3H), 1.80 (m, 2H), 1.60 (m,
6H). 13C NMR (75 MHz, CDCl3): δ 169.3, 126.6, 122.0, 88.4, 87.6,
76.0, 37.3, 25.4, 23.6, 22.9, 22.2.
4-Methyl-1-phenylpent-4-en-2-yn-1-yl Acetate, 5d:15 152 mg,
1
71% yield. H NMR (300 MHz, CDCl3): δ 7.53 (m, 2H), 7.38 (m,
3H), 6.60 (s, 1H), 5.38 (s, 1H), 5.29 (m, 1H), 2.11 (s, 3H), 1.92 (s,
3H). 13C NMR (75 MHz, CDCl3): δ 170.0, 137.4, 129.1, 128.9, 128.0,
126.1, 123.5, 88.4, 84.7, 66.2, 23.4, 21.4.
Characterizations of Alkenyl Propargylic Esters 3, 5, and 10.
2-Methyldodec-1-en-3-yn-5-yl But-3-enoate, 3: 147 mg, 56% yield.
1H NMR (300 MHz, CDCl3): δ 5.90 (m, 1H), 5.48 (t, 1H, J = 6.8
4-Methyl-1-(p-tolyl)pent-4-en-2-yn-1-yl Acetate, 5e: 171 mg, 75%
1
yield. H NMR (300 MHz, CDCl3): δ 7.44 (d, 2H, J = 8.1 Hz), 7.21
Hz), 5.27 (s, 1H), 5.21 (m, 1H), 5.18 (m, 1H), 5.13 (t, 1H, J = 1.4
(d, 2H, J = 7.8 Hz), 6.59 (s, 1H), 5.39 (s, 1H), 5.30 (m, 1H), 2.38 (s,
D
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3H), 2.10 (s, 3H), 1.93 (m, 3H). 13C NMR (75 MHz, CDCl3): δ
170.0, 139.1, 134.6, 129.6, 128.0, 126.2, 123.3, 88.2, 85.0, 66.1, 23.4,
21.5, 21.4. Colorless liquid. HRMS (EI) for C15H16O2 (M) Calcd:
228.1150. Found: 228.1154.
3H), 1.91 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 169.4, 141.8, 140.2,
135.2, 130.4, 129.4, 128.9, 128.5, 128.4, 128.1, 127.8, 126.3, 123.2,
88.5, 85.5, 64.1, 23.4, 21.1. Brown oil. HRMS (EI) for C20H18O2 (M)
Calcd: 290.1307. Found: 290.1301.
4-Methyl-1-(o-tolyl)pent-4-en-2-yn-1-yl Acetate, 5f: 157 mg, 69%
1-(2′,4′-Difluoro-[1,1′-biphenyl]-2-yl)-4-methylpent-4-en-2-yn-1-
1
1
yield. H NMR (300 MHz, CDCl3): δ 7.62 (m, 1H), 7.27 (m, 2H),
yl Acetate, 5p: 157 mg, 48% yield. H NMR (300 MHz, CDCl3): δ
7.20 (m, 1H), 6.71 (s, 1H), 5.37 (s, 1H), 5.30 (m, 1H), 2.45 (s, 3H),
2.12 (s, 3H), 1.91 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 169.9,
136.5, 135.5, 131.0, 129.1, 128.3, 126.5, 126.2, 123.3, 88.2, 84.7, 64.3,
23.4, 21.2, 19.3. Colorless liquid. HRMS (EI) for C15H16O2 (M)
Calcd: 228.1150. Found: 228.1152.
7.84 (dd, 1H, J = 7.6, 1.5 Hz), 7.52−7.40 (m, 2H), 7.30−7.22 (m,
2H), 6.98−6.88 (m, 2H), 6.39 (s, 1H), 5.33 (s, 1H), 5.27 (m, 1H),
2.00 (s, 3H), 1.88 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 169.5,
163.1 (dd, J = 228.0, 11.6 Hz), 159.9 (dd, J = 228.0, 11.6 Hz), 136.2,
134.4, 132.6, 131.0, 129.0, 128.7, 126.2, 123.3, 111.6 (dd, J = 21.1, 3.0
Hz,), 111.3, 104.3 (t, J = 25.7 Hz), 88.5, 84.7, 64.1, 63.8, 23.3, 21.0.
Brown oil. HRMS (EI) for C20H16F2O2 (M) Calcd: 326.1118. Found:
326.1109.
1-(4-Chlorophenyl)-4-methylpent-4-en-2-yn-1-yl Acetate, 5g: 144
1
mg, 58% yield. H NMR (300 MHz, CDCl3): δ 7.46 (d, 2H, J = 8.1
Hz), 7.33 (d, 2H, J = 8.1 Hz), 6.55 (s, 1H), 5.37 (s, 1H), 5.30 (m,
1H), 2.09 (s, 3H), 1.89 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 169.8,
136.0, 135.0, 129.4, 129.0, 126.0, 123.7, 88.7, 84.3, 65.4, 23.3, 21.2.
Colorless liquid. HRMS (EI) for C14H13ClO2 (M) Calcd: 248.0604.
Found: 248.0601.
2-Methyl-5-phenylpent-1-en-4-yn-3-yl Acetate, 10a: 174 mg, 81%
1
yield. H NMR (300 MHz, CDCl3): δ 7.45 (m, 2H), 7.31 (m, 3H),
6.07 (s, 1H), 5.29 (s, 1H), 5.05 (s, 1H), 2.01 (s, 3H), 1.91 (s, 3H). 13C
NMR (75 MHz, CDCl3): δ 169.9, 140.6, 132.1, 129.0, 128.5, 122.4,
115.2, 86.5, 85.0, 57.8, 21.3, 18.6. Colorless liquid. HRMS (EI) for
C14H14O2 (M) Calcd: 214.0994. Found: 214.0999.
1-(2,6-Dichlorophenyl)-4-methylpent-4-en-2-yn-1-yl Acetate, 5h:
1
181 mg, 64% yield. H NMR (300 MHz, CDCl3): δ 7.35−7.13 (m,
4H), 5.32 (s, 1H), 5.24 (m, 1H), 2.07 (s, 3H), 1.85 (s, 3H). 13C NMR
(75 MHz, CDCl3): δ 169.6, 135.7, 132.6, 130.4, 129.4, 126.2, 123.8,
88.1, 82.6, 62.3, 23.2, 20.9. Colorless liquid. HRMS (EI) for
C14H12Cl2O2 (M) Calcd: 282.0214. Found: 282.0211.
1
2-Methylnon-1-en-4-yn-3-yl Acetate, 10b: 159 mg, 82% yield. H
NMR (300 MHz, CDCl3): δ 5.80 (s, 1H), 5.18 (s, 1H), 4.96 (s, 1H),
2.22 (td, 2H, J = 6.9, 1.8 Hz), 2.09 (s, 3H), 1.82 (s, 3H), 1.49 (m, 2H),
1.38 (m, 2H), 0.89 (t, 3H, J = 7.2 Hz). 13C NMR (75 MHz, CDCl3): δ
170.0, 141.1, 114.5, 87.6, 76.1, 67.8, 30.7, 22.1, 21.3, 18.6, 18.5, 13.8.
Colorless liquid. HRMS (M) for C12H18O2 Calcd: 194.1307. Found:
194.1311.
4-Methyl-1-(4-nitrophenyl)pent-4-en-2-yn-1-yl Acetate, 5i: 181
mg, 70% yield.1H NMR (300 MHz, CDCl3): δ 8.24 (m, 2H), 7.69 (m,
2H), 6.63 (s, 1H), 5.39 (s, 1H), 5.32 (m, 1H), 2.14 (d, 3H, J = 1.8
Hz), 1.90 (m, 3H). 13C NMR (75 MHz, CDCl3): δ 169.7, 148.3,
144.2, 128.7, 125.7, 124.2, 124.1, 89.5, 83.3, 65.0, 23.2, 21.2. Light
brown liquid. HRMS (EI) for C14H13NO4 (M) Calcd: 259.0845.
Found: 259.0844.
General Procedure for [RhCl(CO)2]2-Catalyzed [4 + 1]
Cycloaddition of the Alkenyl Propargylic Acetates with CO.
Under nitrogen, an alkenyl propargyl acetate 5 or 10 (0.20 mmol) and
[RhCl(CO)2]2 (7.8 mg, 0.10 equiv) were weighed into a tared two-
neck round-bottom flask and dissolved with DCE (5 mL). The flask
was fitted with a reflux condenser fit with a septum, and the side arm
of the flask was also fitted with a septum. The solution was bubbled
with CO gas for 2 min through the side arm and a vent needle in the
septum of the reflux condenser. The solution was then placed under a
CO atmosphere by using a balloon. The reaction mixture was heated
at reflux until the reaction was determined to be complete by TLC
(4−24 h). The resulting solution was cooled to room temperature, and
the CO was released cautiously in the hood. The reaction mixture was
concentrated, and the E/Z ratio of the products was determined by 1H
NMR analysis before the crude product was purified by flash column
chromatography eluted with hexanes/ethyl acetate.
Characterizations of the [4 + 1] Cycloaddition Products 4, 6,
and 11. E-2-Methyl-5-octylidene-4-oxocyclopent-1-en-1-yl But-3-
enoate, 4: <20 mg, < 40% yield. 1H NMR (300 MHz, CDCl3): δ 6.18
(t, 1H, J = 8.1 Hz), 6.01 (m, 1H), 5.29 (m,1H), 5.25 (m, 1H), 3.31
(dt, 2H, J = 7.2, 1.2 Hz), 2.97 (d, 2H, J = 0.9 Hz), 2.24 (q, 2H, J = 7.5
Hz), 1.77 (s, 3H), 1.40 (m, 2H), 1.26 (m, 8H), 0.87 (t, 3H, J = 6.0
Hz). 13C NMR (75 MHz, CDCl3): δ 199.9, 168.6, 145.4, 132.5, 131.6,
129.3, 127.8, 120.0, 44.5, 39.1, 32.0, 29.6, 29.4, 29.3, 27.2, 22.9, 14.3,
12.8. Brown oil. HRMS (EI) for C18H26O3 (M) Calcd: 290.1882.
Found: 290.1879.
4-Methyl-1-(2-nitrophenyl)pent-4-en-2-yn-1-yl Acetate, 5j: 176
1
mg, 68% yield. H NMR (300 MHz, CDCl3): δ 7.97 (d, 1H, J = 8.1
Hz), 7.90 (d, 1H, J = 8.1 Hz), 7.68 (t, 1H, J = 7.8 Hz), 7.52 (t, 1H, J =
7.8 Hz), 7.13 (s, 1H), 5.36 (s, 1H), 5.30 (m, 1H), 2.10 (s, 3H), 1.88
(s, 3H). 13C NMR (75 MHz, CDCl3): δ 169.4, 148.1, 133.7, 132.3,
129.8, 129.6, 125.8, 125.0, 124.0, 89.0, 83.1, 62.3, 23.3, 20.9. Brown oil.
HRMS (EI) for C14H13NO4 (M) Calcd: 259.0845. Found: 259.0842.
4-Methyl-1-(4-(trifluoromethyl)phenyl)pent-4-en-2-yn-1-yl Ace-
1
tate, 5k: 211 mg, 75% yield. H NMR (300 MHz, CDCl3): δ 7.65
(m, 4H), 6.62 (s, 1H), 5.38 (s, 1H), 5.31 (m, 1H), 2.12 (s, 3H), 1.91
(s, 3H). 13C NMR (150 MHz, CDCl3): δ 169.6, 141.1, 130.9 (q, J =
32.3 Hz), 125.64, 125.61, 125.60, 123.9 (q, J = 270.8 Hz), 123.6, 88.8,
83.6, 65.2, 23.0, 20.9. Light brown oil. HRMS (EI) for C15H13F3O2
(M) Calcd: 282.0868. Found: 282.0872.
4-Methyl-1-(2-(trifluoromethyl)phenyl)pent-4-en-2-yn-1-yl Ace-
1
tate, 5l: 194 mg, 69% yield. H NMR (300 MHz, CDCl3): δ 7.96
(d, 1H, J = 7.8 Hz), 7.64 (m, 2H), 7.47 (t, 1H, J = 7.8 Hz), 6.86 (s,
1H), 5.35 (s, 1H), 5.28 (s, 1H), 2.10 (s, 3H), 1.88 (s, 3H). 13C NMR
(150 MHz, CDCl3): δ 169.1, 135.5, 132.3, 129.9, 128.9, 127.6 (q, J =
30.9 Hz), 126.0 (q, J = 5.5 Hz), 125.7, 123.8 (q, J = 272.6 Hz), 123.3,
88.5, 84.0, 62.1, 22.9, 20.7. Light brown oil. HRMS (EI) for
C15H13F3O2 (M) Calcd: 282.0868. Found: 282.0869.
4-Methyl-1-(naphthalen-2-yl)pent-4-en-2-yn-1-yl Acetate, 5m:
1
5-(Cyclohexylmethylene)-2-methyl-4-oxocyclopent-1-en-1-yl Ac-
174 mg, 66% yield. H NMR (300 MHz, CDCl3): δ 8.03 (s, 1H),
1
etate, 6a: 47 mg, 95% yield. E-6a: H NMR (300 MHz, CDCl3): δ
7.84 (m, 3H), 7.67 (m, 1H), 7.51 (m, 2H), 6.81 (s, 1H), 5.44 (s, 1H),
5.33 (m, 1H), 2.15 (s, 3H), 1.96 (s, 3H). 13C NMR (75 MHz,
CDCl3): δ170.0, 134.8, 133.7, 133.3, 128.9, 128.5, 128.0, 127.4, 126.9,
126.7, 126.2, 125.4, 123.6, 88.7, 84.9, 66.4, 23.5, 21.4. Light brown oil.
HRMS (EI) for C18H16O2 (M) Calcd: 264.1150. Found: 264.1151.
4-Methyl-1-(naphthalen-1-yl)pent-4-en-2-yn-1-yl Acetate, 5n:
6.03 (d, 1H, J = 10.5 Hz), 2.96 (s, 2H), 2.42 (m, 1H) 2.29 (s, 3H),
1.78 (s, 3H), 1.65 (m, 4H), 1.19 (m, 6H). 13C NMR (75 MHz,
CDCl3): δ 200.5, 168.0, 145.3, 136.1, 130.8, 127.9, 44.5, 36.6, 32.9,
26.0, 25.9, 20.8, 12.8. White solid, mp 98−100 °C. HRMS (EI) for
C15H20O3 (M) Calcd: 248.1412. Found: 248.1410.
1
2-Methyl-4-oxo-5-propylidenecyclopent-1-en-1-yl Acetate, 6b: 36
mg, 92% yield. E-6b: 1H NMR (300 MHz, CDCl3): δ 6.16 (t, 1H, J =
8.1 Hz), 2.96 (s, 2H), 2.27 (m, 5H) 1.78 (s, 3H), 1.05 (t, 3H, J = 7.6
Hz). 13C NMR (75 MHz, CDCl3): δ 199.9, 168.1, 145.5, 132.6, 132.1,
127.8, 44.5, 20.8, 20.5, 13.9., 12.7. Colorless oil. HRMS (EI) for
166 mg, 63% yield. H NMR (300 MHz, CDCl3): δ 8.25 (d, 1H, J
= 8.4 Hz), 7.80 (m, 3H), 7.53 (m, 3H), 7.26 (s, 1H), 5.40 (s, 1H),
5.30 (m, 1H), 2.14 (s, 3H), 1.93 (s, 3H). 13C NMR (75 MHz,
CDCl3): δ 170.1, 134.2, 132.7, 130.8, 130.2, 129.1, 126.9, 126.2, 125.5,
124.0, 123.5, 89.0, 84.8, 64.6, 23.4, 21.3. Light brown oil. HRMS (EI)
for C18H16O2 (M) Calcd: 264.1150. Found: 264.1152.
1
C11H14O3 (M) Calcd: 194.0943. Found: 194.0934. Z-6b: H NMR
(300 MHz, CDCl3): δ 5.62 (t, 1H, J = 8.0 Hz), 2.93 (s, 2H), 2.70 (m,
5H), 2.29 (s, 3H), 1.77 (s, 3H), 1.03 (t, 3H, J = 7.5 Hz). 13C NMR (75
MHz, CDCl3): δ 201.3, 167.9, 145.3, 135.1, 131.5, 124.1, 45.3, 20.7,
1-([1,1′-Biphenyl]-2-yl)-4-methylpent-4-en-2-yn-1-yl Acetate, 5o:
1
148 mg, 51% yield. H NMR (300 MHz, CDCl3): δ 7.86 (m, 1H),
7.50−7.29 (m, 8H), 6.52 (s, 1H), 5.36 (s, 1H), 5.28 (m, 1H), 2.01 (s,
E
dx.doi.org/10.1021/jo3009403 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
20.6, 13.9., 12.7. Colorless oil. HRMS (EI) for C11H14O3 (M) Calcd:
194.0943. Found: 194.0948.
44.3, 20.3, 13.4. Yellow solid. HRMS (EI) for C15H13NO5 (M) Calcd:
287.0794. Found: 287.0786. Z-6i: H NMR (300 MHz, CDCl3): δ
1
5-Cyclohexylidene-2-methyl-4-oxocyclopent-1-en-1-yl Acetate,
8.18 (d, 2H, J = 7.5 Hz), 8.03 (d, 2H, J = 8.7 Hz), 6.34 (s, 1H), 3.08
(s, 2H), 2.38 (s, 3H), 1.89 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
198.5, 167.6, 148.0, 145.4, 140.3, 134.0, 131.5, 130.7, 125.5, 123.5,
45.1, 20.7, 13.5. Yellow solid. HRMS (EI) for C15H13NO5 (M) Calcd:
287.0794. Found: 287.0786.
1
6c: 23 mg, 50% yield. H NMR (300 MHz, CDCl3): δ 2.96 (t, 2H,
J = 5.6 Hz), 2.90 (s, 2H), 2.41 (t, 2H, J = 5.9 Hz), 2.24 (s, 3H), 1.72
(s, 3H), 1.61 (m, 6H). 13C NMR (75 MHz, CDCl3): δ 202.1, 168.1,
152.1, 145.9, 124.8, 123.9, 45.5, 30.8, 29.7, 28.9, 28.8, 26.5, 21.0, 12.5.
Colorless oil. HRMS (EI) for C14H18O3 (M) Calcd: 234.1256. Found:
234.1261.
2-Methyl-5-(2-nitrobenzylidene)-4-oxocyclopent-1-en-1-yl Ace-
1
tate, 6j: 55 mg, 96% yield. E-6j: H NMR (300 MHz, CDCl3): δ
5-Benzylidene-2-methyl-4-oxocyclopent-1-en-1-yl Acetate, 6d:
41 mg, 85% yield. E-6d: H NMR (600 MHz, CDCl3): δ 7.39 (d,
8.15 (d, 1H, J = 7.5 Hz), 7.61 (t, 1H, J = 7.8 Hz), 7.51 (t, 1H, J = 7.2
Hz), 7.34 (m, 2H), 3.09 (s, 2H), 1.81 (s, 3H), 1.56 (s, 3H). 13C NMR
(75 MHz, CDCl3): δ 198.8, 167.3, 148.0, 144.9, 133.0, 132.8, 132.4,
132.1, 130.9, 129.1, 125.0, 122.8, 44.4, 19.8, 13.1. Yellow solid, mp
65−67 °C. HRMS (EI) for C15H13NO5 (M) Calcd: 287.0794. Found:
1
2H, J = 7.2 Hz), 7.34 (t, 2H, J = 7.2 Hz), 7.31 (t, 1H, J = 6.9 Hz), 7.13
(s, 1H), 3.08 (d, 2H, J = 1.2 Hz), 1.87 (s, 3H), 1.80 (s, 3H). 13C NMR
(150 MHz, CDCl3): δ 199.9, 167.5, 145.6, 134.4, 131.7, 130.7, 129.9,
128.7, 128.2, 127.5, 44.4, 20.3, 13.0. Colorless oil. HRMS (EI) for
C15H14O3(M) Calcd: 242.0943. Found: 242.0950. Z-6d: 1H NMR
(600 MHz, CDCl3): δ 7.96 (m, 2H), 7.38−7.32 (m, 3H), 6.34 (s, 1H),
3.04 (s, 2H), 2.37(s, 3H), 1.85 (s, 3H). 13C NMR (150 MHz, CDCl3):
δ 198.8, 167.5, 146.2, 134.0, 131.3, 130.8, 129.6, 129.0, 128.1, 125.8,
45.0, 20.5, 12.9. Colorless oil. HRMS (EI) for C15H14O3 (M) Calcd:
242.0943. Found: 242.0938.
1
287.0801. Z-6j: H NMR (300 MHz, CDCl3): δ 8.10 (d, 1H, J = 8.4
Hz), 7.09 (d, 1H, J = 7.5 Hz), 7.59 (t, 1H, J = 7.5 Hz), 7.48 (t, 1H, J =
7.8 Hz), 6.73 (s, 1H), 3.02 (s, 2H), 2.35 (s, 3H), 1.88 (s, 3H). 13C
NMR (75 MHz, CDCl3): δ 198.5, 167.8, 147.8, 146.0, 132.9, 132.7,
132.6, 130.0, 129.5, 129.0, 124.8, 123.3, 45.2, 20.7, 13.3. Brown oil.
HRMS (EI) for C15H13NO5 (M) Calcd: 287.0794. Found: 287.0790.
2-Methyl-4-oxo-5-(4-(trifluoromethyl)benzylidene)cyclopent-1-
en-1-yl Acetate, 6k:19 53 mg, 85% yield. E-6k: H NMR (300 MHz,
1
2-Methyl-5-(4-methylbenzylidene)-4-oxocyclopent-1-en-1-yl Ace-
tate, 6e: 31 mg, 61% yield. E-6e: 1H NMR (600 MHz, CDCl3): δ 7.31
(d, 2H, J = 8.4 Hz), 7.14 (d, 2H, J = 7.8 Hz), 7.10 (s, 1H), 3.07 (d, 2H,
J = 1.2 Hz), 2.36 (s, 3H), 1.88 (s, 3H), 1.86 (d, 3H, J = 0.6 Hz). 13C
NMR (150 MHz, CDCl3): δ 199.9, 167.3, 145.4, 138.8, 131.3, 130.8,
129.94, 129.9, 128.8, 127.6, 44.2, 21.4, 20.2, 12.7. White solid, mp
138−139 °C. HRMS (EI) for C16H16O3(M) Calcd: 256.1099. Found:
CDCl3): δ 7.60 (d, 2H, J = 8.1 Hz), 7.48 (d, 2H, J = 8.1 Hz), 7.09 (s,
1H), 3.10 (s, 2H), 1.88 (s, 3H), 1.78 (s, 3H). 13C NMR (150 MHz,
CDCl3): δ 199.0, 166.9, 145.1, 138.0, 133.0, 132.4, 130.7, 129.8 (m),
124.8 (m), 124.0 (q, J = 258.6 Hz), 44.0, 19.8, 12.8. Yellow solid.
HRMS (ESI) for C16H14F3O3 (MH+) Calcd: 311.0895. Found:
1
311.0889. Z-6k: H NMR (300 MHz, CDCl3): δ 7.99 (d, 2H, J = 7.8
1
256.1104. Z-6e: H NMR (300 MHz, CDCl3): δ 7.88 (d, 2H, J = 8.4
Hz), 7.60 (d, 2H, J = 7.8 Hz), 6.33 (s, 1H), 3.06 (s, 2H), 2.37 (s, 3H),
1.88 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 198.4, 167.4, 146.1,
137.2, 133.1, 130.2, 130.0, 128.0, 126.5, 124.8 (m), 124.1 (q, J = 258.6
Hz), 44.8, 20.3, 13.0. Yellow solid. HRMS (ESI) for C16H14F3O3 (MH
+) Calcd: 311.0895. Found: 311.0891.
Hz), 7.17 (d, 2H, J = 7.8 Hz), 6.31 (s, 1H), 3.03 (s, 2H), 2.37 (s, 6H),
1.84 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 199.1, 167.8, 146.5,
140.3, 131.6, 131.2, 130.7, 129.4, 129.1, 125.2, 45.3, 21.8, 20.7, 13.1.
Yellow solid, mp 85−86 °C. HRMS (EI) for C16H16O3 (M) Calcd:
256.1099. Found: 256.1101.
2-Methyl-5-(2-methylbenzylidene)-4-oxocyclopent-1-en-1-yl Ace-
tate, 6f: 44 mg, 86% yield. E-6f: 1H NMR (300 MHz, CDCl3): δ 7.16
(m, 5H), 3.08 (d, 2H, J = 0.9 Hz), 2.25 (s, 3H), 1.84 (s, 3H), 1.52 (s,
3H). 13C NMR (75 MHz, CDCl3): δ 199.9, 167.6, 145.6, 137.9, 133.7,
132.2, 130.3, 129.9, 129.6, 128.6, 126.6, 125.2, 44.4, 20.3, 19.7, 12.8.
Colorless oil. HRMS (EI) for C16H16O3 (M) Calcd: 256.1099. Found:
256.1091.
2-Methyl-4-oxo-5-(2-(trifluoromethyl)benzylidene)cyclopent-1-
1
en-1-yl Acetate, 6l: 51 mg, 82% yield. E-6l: H NMR (300 MHz,
CDCl3): δ 7.67 (d, 1H, J = 7.5 Hz), 7.51 (t, 1H, J = 7.4 Hz), 7.43 (t,
1H, J = 7.5 Hz), 7.31 (d, 1H, J = 7.5 Hz), 7.26 (s, 1H), 3.10 (s, 2H),
1.83 (s, 3H), 1.55 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 198.9,
166.9, 144.9, 133.5, 133.0, 132.2, 131.1, 130.7, 129.1 (q, J = 29.9 Hz),
128.0, 125.7 (q, J = 4.9 Hz), 123.7 (q, J = 272.2 Hz), 122.7, 44.0, 19.5,
12.8. Yellow solid, mp 92−93 °C. HRMS (ESI) for C16H14F3O3(MH
1
5-(4-Chlorobenzylidene)-2-methyl-4-oxocyclopent-1-en-1-yl Ace-
+) Calcd: 311.0895. Found: 311.0894. Z-6l: H NMR (300 MHz,
tate, 6g:19 38 mg, 69% yield. E-6g: H NMR (300 MHz, CDCl3): δ
1
CDCl3): δ 7.88 (d, 1H, J = 7.8 Hz), 7.65 (d, 1H, J = 7.8 Hz), 7.51 (t,
1H, J = 7.8 Hz), 7.41 (t, 1H, J = 7.8 Hz), 6.64 (s, 1H), 3.03 (s, 2H),
2.35 (s, 3H), 1.87 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 198.1,
167.5, 146.0, 132.8, 132.1, 131.7, 131.0, 128.6, 128.4, 128.2, 125.6 (q, J
= 5.2 Hz), 124.2 (q, J = 271.9 Hz), 123.2, 45.0, 20.3, 12.9. Brown oil.
HRMS (ESI) for C16H14F3O3 (MH+) Calcd: 311.0895. Found:
311.0898.
2-Methyl-5-(naphthalen-2-ylmethylene)-4-oxocyclopent-1-en-1-
yl Acetate, 6m: 51 mg, 88% yield. E-6m: 1H NMR (300 MHz,
CDCl3): δ 7.90 (s, 1H), 7.81 (m, 3H, J = 8.7 Hz), 7.50 (m, 3H), 7.28
(s, 1H), 3.12 (s, 2H), 1.89 (s, 3H), 1.68 (s, 3H). 13C NMR (75 MHz,
CDCl3): δ 199.9, 167.4, 145.7, 133.3, 133.1, 131.9, 131.8, 131.0, 129.7,
128.4, 127.9, 127.8, 127.6, 127.5, 127.0, 126.8, 44.5, 20.3, 13.1. Yellow
solid, mp 49−51 °C. HRMS (EI) for C19H16O3 (M) Calcd: 292.1099.
Found: 292.1105. Z-6m: 1H NMR (300 MHz, CDCl3): δ 8.43 (s, 1H),
8.11 (dd, 1H, J = 8.7, 1.8 Hz), 7.86 (m, 1H), 7.80 (m, 2H), 7.47 (m,
2H), 6.51 (s, 1H), 3.08 (s, 2H), 2.40 (s, 3H), 1.87 (s, 3H). 13C NMR
(75 MHz, CDCl3): δ 199.1, 167.8, 146.6, 134.0, 133.3, 132.0, 131.7,
131.5, 129.2, 129.0, 128.1, 127.8, 127.2, 126.4, 126.1, 45.3, 20.8, 13.2.
Yellow solid, mp 90−91 °C. HRMS (EI) for C19H16O3 (M) Calcd:
292.1099. Found: 292.1107.
7.33 (m, 4H), 7.04 (s, 1H), 3.09 (s, 2H), 1.88 (s, 6H). 13C NMR (150
MHz, CDCl3): δ 199.2, 167.0, 145.1, 134.4, 132.6, 132.1, 131.8, 130.1,
128.1, 125.5, 44.0, 20.0, 12.7. Brown oil. HRMS (EI) for C15H13ClO3
1
(M) Calcd: 276.0553. Found: 276.0558. Z-6g: H NMR (300 MHz,
CDCl3): δ 7.90 (d, 2H, J = 8.4 Hz), 7.33 (m, 2H), 6.27 (s, 1H), 3.04
(s, 2H), 2.37 (s, 3H), 1.85 (s, 3H). 13C NMR (150 MHz, CDCl3): δ
198.7, 167.4, 146.1, 135.3, 132.5, 131.6, 131.3, 128.2, 127.2, 126.4,
44.9, 20.3, 12.9. Brown oil. HRMS (EI) for C15H13ClO3 (M) Calcd:
276.0553. Found: 276.0558.
5-(2,6-Dichlorobenzylidene)-2-methyl-4-oxocyclopent-1-en-1-yl
Acetate, 6h: 52 mg, 84% yield. E-6h: 1H NMR (300 MHz, CDCl3): δ
7.34 (d, 2H, J = 7.8 Hz), 7.19 (t, 1H, J = 8.1 Hz), 6.85 (s, 1H), 3.10 (s,
2H), 1.84 (s, 3H), 1.51 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 198.7,
167.3, 145.3, 135.5, 133.0, 132.5, 129.5, 127.8, 119.9, 44.5, 19.4, 13.1.
White solid, mp 150−151 °C. HRMS (ESI) for C15H13Cl2O3 (MH+)
Calcd: 311.0242. Found: 311.0239. Z-6h: 1H NMR (600 MHz,
CDCl3): δ 7.30 (d, 2H, J = 7.8 Hz), 7.16 (t, 1H, J = 7.8 Hz), 6.23 (s,
1H), 2.99 (d, 2H, J = 1.2 Hz), 2.36 (s, 3H), 1.88 (d, 3H, J = 1.2 Hz).
13C NMR (150 MHz, CDCl3): δ 197.5, 167.3, 145.24, 134.7, 134.6,
132.7, 129.8, 129.1, 127.6, 119.5, 44.6, 20.4, 13.1. Yellow solid, mp
85−87 °C. HRMS (ESI) for C15H13Cl2O3 (MH+) Calcd: 311.0242.
Found: 311.0239.
2-Methyl-5-(naphthalen-1-ylmethylene)-4-oxocyclopent-1-en-1-
yl Acetate, 6n: 49 mg, 84% yield. E-6n: 1H NMR (300 MHz, CDCl3):
δ 7.88 (m, 3H), 7.63 (s, 1H), 7.45 (m, 4H), 3.14 (s, 2H), 1.85 (s, 3H),
1.38 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 199.8, 167.4, 145.6,
133.4, 132.1, 131.7, 131.0, 129.8, 129.1, 128.5, 127.4, 126.9, 126.5,
125.5, 125.2, 124.9, 44.5, 19.7, 13.0. Brown oil. HRMS (EI) for
C19H16O3 (M) Calcd: 292.1099. Found: 292.1108.
2-Methyl-5-(4-nitrobenzylidene)-4-oxocyclopent-1-en-1-yl Ace-
tate, 6i:19 52 mg, 90% yield. E-6i: H NMR (300 MHz, CDCl3): δ
1
8.20 (d, 2H, J = 8.7 Hz), 7.55 (d, 2H, J = 8.4 Hz), 7.06 (s, 1H), 3.13
(s, 2H), 1.90 (s, 3H), 1.86 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
198.8, 167.1, 147.5, 145.4, 141.3, 134.2, 131.5, 130.7, 124.0, 123.4,
F
dx.doi.org/10.1021/jo3009403 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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5-([1,1′-Biphenyl]-2-ylmethylene)-2-methyl-4-oxocyclopent-1-en-
1-yl Acetate, 6o: 52 mg, 82% yield. E-6o: 1H NMR (300 MHz,
CDCl3): δ 7.40−7.32 (m, 9H), 6.93 (s, 1H), 3.07 (s, 2H), 1.90 (s,
3H), 1.67 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 199.7, 167.9, 142.7,
140.3, 132.5, 132.0, 130.8, 130.0, 129.9, 129.0, 128.4, 128.3, 127.8,
126.4, 44.5, 20.1, 12.8. Light yellow solid, mp 110−112 °C. HRMS
(EI) for C21H18O3 (M) Calcd: 318.1256. Found: 318.1249.
(e) Crimmins, M. T.; Jung, D. K.; Gray, J. L. J. Am. Chem. Soc. 1993,
115, 3146−3155. (f) Roethle, P. A.; Trauner, D. Org. Lett. 2006, 8,
345. (g) Trost, B. M.; Weiss, A. H. Angew. Chem., Int. Ed. 2007, 46,
7664−7666. (h) Imagawa, H.; Saijo, H.; Kurisaki, T.; Yamamoto, M.
K.; Fukuyama, Y.; Nishizawa, M. Org. Lett. 2009, 11, 1253−1255.
(4) Using Rh: (a) Li, X.; Zhang, M.; Shu, D.; Robichaux, P. J.;
Huang, S.; Tang, W. Angew. Chem., Int. Ed. 2011, 50, 10421−10424.
(b) Shu, D.; Li, X.; Zhang, M.; Robichaux, P. J.; Tang, W. Angew.
Chem., Int. Ed. 2011, 50, 1346−1349. (c) Shibata, Y.; Noguchi, K.;
Tanaka, K. J. Am. Chem. Soc. 2010, 132, 7896−7898. (d) Brancour, C.;
Fukuyama, T.; Ohta, Y.; Ryu, I.; Dhimane, A.-L.; Fensterbank, L.;
Malacria, M. Chem. Commun. 2010, 46, 5470−5472. (e) Li, X.; Huang,
S.; Schienebeck, C. M.; Shu, D.; Tang, W. Org. Lett. 2012, 14, 1584−
1587. (f) Shu, X. Z.; Huang, S. Y.; Shu, D. X.; Guzei, I. A.; Tang, W. P.
Angew. Chem., Int. Ed. 2011, 50, 8153−8156. (g) Zhang, D.-H.; Shi, M.
Tetrahedron Lett. 2012, 53, 487−490. (h) Shibata, Y.; Noguchi, K.;
Tanaka, K. Org. Lett. 2010, 12, 5596−5599. (i) Shibata, Y.; Noguchi,
K.; Tanaka, K. J. Am. Chem. Soc. 2010, 132, 7896−7898. (j) Fukuyama,
T.; Ohta, Y.; Brancour, C.; Miyagawa, K.; Ryu, I.; Dhimane, A.;
Fensterbank, L.; Malacria, M. Chem.Eur. J. 2012, 18, 7243−7247.
(5) Using Au: (a) Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste,
F. D. J. Am. Chem. Soc. 2005, 127, 18002−18003. (b) Gorin, D. J.;
Dube, P.; Toste, F. D. J. Am. Chem. Soc. 2006, 128, 14480−14481.
(c) Gorin, D. J.; Watson, I. D. G.; Toste, F. D. J. Am. Chem. Soc. 2008,
130, 3736−3737. (d) Li, G.; Zhang, G.; Zhang, L. J. Am. Chem. Soc.
5-((2′,4′-Difluoro-[1,1′-biphenyl]-2-yl)methylene)-2-methyl-4-ox-
1
ocyclopent-1-en-1-yl Acetate, 6p: 52 mg, 73% yield. E-6p: H NMR
(300 MHz, CDCl3): δ 7.38 (m, 4H), 7.16 (m, 1H), 6.87 (m, 3H), 3.04
(s, 2H), 1.87 (s, 3H), 1.67 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
199.5, 167.8, 163.0 (dd, J = 238.4, 12.0 Hz), 159.5 (dd, J = 238.9, 12.0
Hz), 145.5, 135.5, 133.6, 133.5, 133.4, 132.5, 130.8, 130.7, 130.6,
128.6, 127.3, 126.7, 111.4 (dd, J = 20.9, 11.3 Hz), 104.3 (t, J = 25.6
Hz) 44.4, 20.0, 12.9. Light yellow solid, mp 172−173 °C. HRMS
(ESI) for C21H17F2O3 (MH+) Calcd: 355.1146. Found: 355.1148.
(3-Methyl-5-oxocyclopent-2-en-1-ylidene)(phenyl)methyl Ace-
1
tate, 11a: 27 mg, 56% yield. Z-11a: H NMR (600 MHz, CDCl3):
δ 7.53 (m, 2H), 7.41 (m, 3H), 6.22 (m, 1H), 2.92 (s, 2H), 2.35 (s,
3H), 1.98 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 202.2, 169.1,
144.1, 143.1, 134.7, 129.8, 128.5, 128.1, 127.2, 126.1, 46.7, 20.9, 18.0.
Brown oil. HRMS (EI) for C15H14O3 (M) Calcd: 242.0943. Found:
242.0948.
1-(3-Methyl-5-oxocyclopent-2-en-1-ylidene)pentyl Acetate, 11b:
1
33 mg, 74% yield. Z-11b: H NMR (300 MHz, CDCl3): δ 6.29 (m,
1H), 2.83 (m, 2H), 2.33 (t, 2H, J = 7.4 Hz), 2.26 (s, 3H), 1.95 (s, 3H),
1.52 (m, 2H), 1.37 (m, 2H), 0.91 (t, 3H, J = 7.2 Hz). 13C NMR (75
MHz, CDCl3): δ 201.9, 169.1, 149.0, 140.5, 127.2, 125.2, 47.1, 32.8,
28.5, 22.6, 21.1, 18.1, 14.0. Brown oil. HRMS (EI) for C13H18O3 (M)
Calcd: 222.1256. Found: 222.1261.
̀ ̀
2008, 130, 3740−3741. (e) Marion, N.; de Fremont, P.; Lemiere, G.;
Stevens, E. D.; Fensterbank, L.; Malacria, M.; Nolan, S. P. Chem.
Commun. 2006, 2048−2050. (f) Zhang, L. J. Am. Chem. Soc. 2005, 127,
̀ ̀
16804−16805. (g) Marion, N.; Díez-Gonzalez, S.; de Fremont, P.;
Noble, A. R.; Nolan, S. P. Angew.Chem., Int. Ed. 2006, 45, 3647−3650.
ASSOCIATED CONTENT
* Supporting Information
(h) Mamane, V.; Gress, T.; Krause, A.; Furstner, A. J. Am. Chem. Soc.
̈
■
2004, 126, 8654−8655. (i) Zhang, D.-H.; Yao, L.-F.; Wei, Y.; Shi, M.
S
Angew. Chem., Int. Ed. 2011, 50, 2583−2587.
Detailed synthesis and characterization of the compounds are
provided. This material is available free of charge via the
Internet at http://pubs.acs.org.
(6) Using Pt: (a) Mainetti, E.; Mouries, V.; Fensterbank, L.;
Malacria, M.; Marco-Contelles, J. Angew. Chem., Int. Ed. 2002, 41,
2132−2135. (b) Harrak, Y.; Blaszykowski, C.; Bernard, M.; Cariou, K.;
̀
Mainetti, E.; Mouries, V.; Dhimane, A. -L.; Fensterbank, L.; Malacria,
AUTHOR INFORMATION
Corresponding Author
*E-mail: xqyu@scu.edu.cn (X.-Q.Y.), lp6n@virginia.edu (L.P.).
■
M. J. Am. Chem. Soc. 2004, 126, 8656−8657. (c) Prasad, B. A. B.;
Yoshimoto, F. K.; Sarpong, R. J. Am. Chem. Soc. 2005, 127, 12468−
12469. (d) Pujanauski, B. G.; Prasad, B. A. B.; Sarpong, R. J. Am.
Chem. Soc. 2006, 128, 6786. (e) Ji, K.-G.; Shu, X.-Z.; Chen, J.; Zhao,
S.-C.; Zheng, Z.-J.; Lu, L.; Liu, X.-Y.; Liang, Y. M. Org. Lett. 2008, 10,
3919−3922. (f) Cho, E. J.; Kim, M.; Lee, D. Org. Lett. 2006, 8, 5413−
5416. (g) Zheng, H.; Xie, X. G.; Yang, J.; Zhao, C. G.; Jing, P.; Fang, B.
W.; She, X. G. Org. Biomol. Chem. 2011, 9, 7755−7762.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Partial support of this work from the U.S. National Science
Foundation (CHE-0717995 and ECCS-0708923) is gratefully
acknowledged.
(7) Using Ru: (a) Miki, K.; Ohe, K.; Uemura, S. J. Org. Chem. 2003,
68, 8505−8513. (b) Tenaglia, A.; Marc, S. J. Org. Chem. 2006, 71,
3569−3575. (c) Kikuchi, H.; Uno, M.; Takahashi, S. Chem. Lett. 1997,
1273−1274. (d) Villeneuve, K.; Tam, W. Organometallics 2006, 25,
843−848.
(8) Using Pd: (a) Rautenstrauch, V. J. Org. Chem. 1984, 49, 950−
952. (b) Mandai, T.; Tsuji, J.; Tsujiguchi, Y.; Saito, S. J. Am. Chem. Soc.
1993, 115, 5865−5866. (c) Kato, K.; Nouchi, H.; Ishikura, K.;
Takaishi, S.; Motodate, S.; Tanaka, H.; Okudaira, K.; Mochida, T.;
Nishigaki, R.; Shigenobu, K.; Akita, H. Tetrahedron 2006, 62, 2545−
2554. (d) Using Pd(II) and Hg(II): Caruana, P. A.; Frontier, A. J.
Tetrahedron 2007, 63, 10646−10656. (e) Kato, K.; Teraguchi, R.;
Yamamura, S.; Mochida, T.; Akita, H.; Peganova, T. A.; Vologdin, N.
V.; Gusev, O. V. Synlett 2007, 638−642. (f) Kato, K.; Teraguchi, R.;
Motodate, S.; Uchida, A.; Mochida, T.; Peganova, T. A.; Vologdin, N.
V.; Akita, H. Chem. Commun. 2008, 3687−3689.
(9) (a) Using Re and W: Saito, K.; Onizawa, Y.; Kusama, H.;
Iwasawa, N. Chem.Eur. J. 2010, 16, 4716−4720. (b) Using Cu, Ag,
and Au: Schwier, T.; Sromek, A. W.; Yap, D. M. L.; Chernyak, D.;
Gevorgyan, V. J. Am. Chem. Soc. 2007, 129, 9868−9878. (c) Using Pt
́ ́
and Cu: Barluenga, J.; Riesgo, L.; Vicente, R.; Lopez, L. A.; Tomas, M.
J. Am. Chem. Soc. 2007, 129, 7772−7773. (d) Using Au and Pt:
Brabander, J. K. D.; Liu, B.; Qian, M. Org. Lett. 2008, 10, 2533−2536.
REFERENCES
■
(1) (a) Frantz, D. E.; Fassler, R.; Tomooka, C. S.; Carreira, E. M. Acc.
̈
Chem. Res. 2000, 33, 373−381. (b) Pu, L. Tetrahedron 2003, 59,
9873−9886. (c) Cozzi, P. G.; Hilgraf, R.; Zimmermann, N. Eur. J. Org.
Chem. 2004, 4095−4105. (d) Lu, G.; Li, Y.-M.; Li, X.-S.; Chan, A. S.
C. Coord. Chem. Rev. 2005, 249, 1736−1744. (e) Trost, B. M.; Weiss,
A. H. Adv. Synth. Catal. 2009, 351, 963−983. (f) Gao, G.; Pu, L. Sci.
China: Chem. 2010, 53, 21−35.
(2) (a) Tejedor, D.; Lop
G.; García-Tellado, F. Angew. Chem., Int. Ed. 2009, 48, 2090−2098.
(b) Guillarme, S.; Ple, K.; Banchet, A.; Liard, A.; Haudrechy, A. Chem.
́ ́
ez-Tosco, S.; Cruz-Acosta, F.; Mendez-Abt,
́
Rev. 2006, 106, 2355−2403. (c) Detz, R. J.; Henk Hiemstra, H.; van
Maarseveen, J. H. Eur. J. Org. Chem. 2009, 6263−6276.
(3) Selected applications of chiral propargylic alcohols in synthesis:
(a) Trost, B. M.; Muller, T. J. J. J. Am. Chem. Soc. 1994, 116, 4985−
̈
4986. (b) Arcadi, A.; Cacchi, S.; Fabrizi, G.; Marinelli, F.; Pace, P. Eur.
J. Org. Chem. 1999, 3305−3313. (c) Marshall, J. A.; Chobanian, H. R.;
Yanik, M. M. Org. Lett. 2001, 3, 3369−3372. (d) Alfonsi, M.; Arcadi,
A.; Chiarini, M.; Marinelli, F. J. Org. Chem. 2007, 72, 9510−9517.
G
dx.doi.org/10.1021/jo3009403 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(e) Using Ti: Zhang, Z.; Shi, M. Tetrahedron Lett. 2011, 52, 6541−
6544.
(10) Reviews: (a) Marco-Contelles, J.; Soriano, E. Chem.Eur. J.
2007, 13, 1350−1357. (b) Marion, N.; Nolan, S. P. Angew. Chem., Int.
Ed. 2007, 46, 2750−2752.
(11) (a) Rajaram, A. R.; Pu, L. Org. Lett. 2006, 8, 2019−2021.
(b) Zhou, L.-H.; Yu, X.-Q.; Pu, L. J. Org. Chem. 2009, 74, 2013−2017.
(c) Yang, Y.; Turlington, M.; Yu, X.-Q.; Pu, L. Chem.Eur. J. 2009,
15, 5104−5107.
(12) Yang, Y.; Turlington, M.; Yu, X.-Q.; Pu, L. J. Org. Chem. 2009,
74, 8681−8689.
(13) Turlington, M.; Yue, Y.; Yu, X.-Q.; Pu, L. J. Org. Chem. 2010, 75,
6941−6952.
(14) (a) Turlington, M.; Du, Y.-H.; Ostrum, S. G.; Santosh, V.;
Wren, K.; Lin, T.; Sabat, M.; Pu, L. J. Am. Chem. Soc. 2011, 133,
11780−11794. (b) Turlington, M.; Pu, L. Org. Lett. 2011, 13, 4332−
4335.
(15) Zhang, L.; Wang, S. J. Am. Chem. Soc. 2006, 128, 1442−1443.
(16) Tao, B.; Ruble, J. C.; Hoic, D. A.; Fu, G. C. J. Am. Chem. Soc.
1999, 121, 5091−5092.
(17) Cordonnier, M.-C.; Blanc, A.; Pale, P. Org. Lett. 2008, 10,
1569−1572.
(18) (a) Murakami, M.; Itami, K.; Ito, Y. Angew. Chem., Int. Ed. Engl.
1995, 34, 2691−1694. (b) Murakami, M.; Itami, K.; Ito, Y. J. Am.
Chem. Soc. 1996, 118, 11672−11673. (c) Murakami, M.; Itami, K.; Ito,
Y. J. Am. Chem. Soc. 1997, 119, 2950−2951.
(19) The NMR spectra were obtained for the mixture of the E and Z
products.
H
dx.doi.org/10.1021/jo3009403 | J. Org. Chem. XXXX, XXX, XXX−XXX