Palladium-catalyzed asymmetric formal [3+2] cycloaddition of vinyl cyclopropanes and β,γ-unsaturated α-keto esters: An effective route to highly functionalized cyclopentanes

Article abstract of DOI:10.1021/om300896z

Palladium-catalyzed asymmetric formal [3+2] cycloaddition of vinyl cyclopropanes and β,γ-unsaturated α-keto esters proceeded smoothly in the presence of chiral imidazoline-phosphine ligands to give the corresponding highly functionalized cyclopentanes in

Full text of DOI:10.1021/om300896z

Article
pubs.acs.org/Organometallics
Palladium-Catalyzed Asymmetric Formal [3+2] Cycloaddition of Vinyl
Cyclopropanes and β,γ-Unsaturated α‑Keto Esters: An Effective Route
to Highly Functionalized Cyclopentanes
Liang-yong Mei,† Yin Wei,‡ Qin Xu,*,† and Min Shi*,†,‡
†Key Laboratory for Advanced Materials and Institute of Fine Chemicals, School of Chemistry & Molecular Engineering, East China
University of Science and Technology, 130 Mei-Long Road, Shanghai 200237, China
‡State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354
Fenglin Road, Shanghai 200032, China
S
* Supporting Information
ABSTRACT: Palladium-catalyzed asymmetric formal [3+2] cycloaddition of vinyl
cyclopropanes and β,γ-unsaturated α-keto esters proceeded smoothly in the presence
of chiral imidazoline−phosphine ligands to give the corresponding highly function-
alized cyclopentanes in good yields along with high diastereo- and enantioselectivities
under mild conditions.
Scheme 1. Palladium-Catalyzed Cycloaddition of Vinyl
Cyclopropanes 1 with Electron-Deficient Olefins
INTRODUCTION
■
a
Cyclopentanes containing multiple stereocenters have been
widely used as important building blocks in pharmaceuticals,
agrochemicals, and materials.1 The development of asymmetric
synthetic methodologies for producing highly functionalized
cyclopentanes is highly desirable. An effective method used to
synthesize this interesting scaffold would be a metal-catalyzed
asymmetric formal [3+2] cycloaddition between 1,3-dipolar
species and an electron-deficient olefin.
Recently, as a new family of “three-carbon-atom” precursors
for asymmetric cycloadditions, vinyl cyclopropanes bearing
electron-withdrawing groups have attracted much attention.2
By generating 1,3-dipolar equivalents in the presence of Pd(0)
catalysts and subsequent trapping with a dipolarophile such as
olefins,2e isocyanates,3,4 carbodiimides,5 aldehydes,6 and
azlactone,2g vinyl cyclopropanes can provide direct routes to
different substituted five-membered rings. The pioneering work
on this topic has been explored by Tsuji and co-workers
(Scheme 1).2e The cycloaddition reaction proceeded via
zwitterionic (π-allyl) palladium intermediate 2, generated by
ring-opening of vinylcyclopropane 1 in the presence of Pd(0)
catalyst, followed by the reaction with the electron-deficient
olefin to give intermediate 3, which undergoes intramolecular
nucleophilic attack, producing the five-membered product 4.
Later, in a related process, Johnson and co-workers showed
Pd(0)-catalyzed [3+2] cycloaddition of vinylcyclopropane 1
with aldehydes to afford 2,5-cis-disubstituted tetrahydrofuran
derivatives in high yields and diastereoselectivities.6a Afterward,
a
EWG = electron-withdrawing groups.
Stoltz et al. reported a palladium-catalyzed addition of
vinylcyclopropane 1 with a β-nitrostyrene to rapidly assemble
the cyclopentane core of Melodinus alkaloids.7 At the same
time, Trost et al. introduced palladium-catalyzed [3+2]
cycloaddition of vinyl cyclopropanes with alkylidene azlactones
to afford the corresponding cyclopentanes bearing three
stereogenic centers in good yields and good enantio- and
diastereoselectivities.2g All these findings aroused our interest in
Received: September 19, 2012
Published: October 19, 2012
© 2012 American Chemical Society
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exploring Pd(0)-catalyzed [3+2] cycloaddition of vinylcyclo-
propanes 1 with other types of activated olefins.
dimethyl 3-(2-ethoxy-2-oxoacetyl)-2-phenyl-4-vinylcyclopen-
tane-1,1-dicarboxylate (6a) was obtained in 67% yield, with
13:1 dr and 92% ee in toluene (Table 1, entry 1). The
examination of solvent effects revealed that the reaction in
toluene provided a higher diastereoselectivity and better
enantiomeric excess than those in tetrahydrofuran (THF),
acetonitrile (CH3CN), dichloromethane (DCM), N,N-dimeth-
yl formamide (DMF), dimethyl sulfoxide (DMSO), or diethyl
ether (Et2O), albeit in a slightly lower yield (Table 1, entry 1 vs
2−7). Raising the concentration of reaction mixtures from 0.1
to 0.2 M in toluene at room temperature afforded the
corresponding product 6a in 93% yield, along with 19:1 dr
and 92% ee (Table 1, entry 8).
We previously reported the development of novel chiral
imidazoline−phosphines L1−L5 with a 1,1′-binaphthalene
framework as new types of N,P ligands in both palladium-
catalyzed asymmetric allylic alkylation8a and zinc(II)-catalyzed
Mannich-type difluorination of hydrazones with difluoroenox-
ysilanes,8b affording the corresponding products with good
results (Figure 1). Since these chiral imidazoline−-phosphine--
Using toluene as solvent, other chiral ligands were screened,
and the results are shown in Table 2. Ligands (aS,R,R)-L2 and
(aR,S,S)-L4 provided the product 6a in 26% and 31% yields
along with 77% and −78% ee values as well as 2:1 dr,
respectively (Table 2, entries 1 and 3). Ligand (aR,R,R)-L3
afforded the product 6a in 90% yield along with 90% ee and
10:1 dr as well as opposite absolute configuration (Table 2,
entry 2). Meanwhile, ligand (aR,S,S)-L5 afforded the product
6a in 23% yield, along with −69% ee and 2:1 dr (Table 2, entry
4). For comparison, we also examined the chiral phosphine−
oxazoline ligands L6 and L7 in this reaction under identical
conditions.9 The use of chiral phosphine−oxazoline ligand
(aR,S)-L6 resulted in a low yield and poor diastereoselectivity
and enantioselectivity (Table 2, entry 5), while ligand (aS,S)-L7
afforded 6a in 93% yield with poor dr and low ee value,
suggesting that axially chiral imidazoline−phosphine ligand L1
was the best ligand for this reaction (Table 2, entry 6). As
compared with the opposite ee values using (aS,S,S)-L1,
(aS,R,R)-L2, and (aS,S)-L7 with (aR,R,R)-L3, (aR,S,S)-L4,
(aR,S,S)-L5, and (aR,S)-L6, we found that the absolute
configuration of product 6a is determined by the axial chirality
of the ligands.
Figure 1. Novel chiral imidazoline−phosphine-type ligands.
palladium(II) complexes are efficient catalysts for asymmetric
allylic alkylation reactions, we envisaged using these new chiral
ligands in Pd(0)-catalyzed ring-opening of 1 and the
subsequent cycloaddition with β,γ-unsaturated α-keto esters.
RESULTS AND DISCUSSION
■
Initial examinations using dimethyl 2-vinylcyclopropane-1,1-
dicarboxylate (1a) and (E)-ethyl 2-oxo-4-phenylbut-3-enoate
(5a) as the model substrates in the presence of chiral
imidazoline−phosphine-type ligand (aS,S,S)-L1 and Pd2(dba)3
were aimed at screening the optimal conditions, and the results
of these experiments are summarized in Table 1. Delightfully,
The substrate scope was next investigated under the
optimized conditions, and the results are shown in Table 3.
When R1 is an electron-rich aromatic ring, the reactions
proceeded smoothly to give the corresponding cyclopentanes
6b, 6c, and 6g−6k in good yields with excellent diaster-
eoselectivities and 90−98% ee values, respectively (Table 3,
entries 1, 2, and 6−10). However, when R1 is an electron-
deficient aromatic ring, the corresponding adducts 6d and 6e
were obtained in moderate yields along with relatively lower ee
values, although the diastereoselectivities were excellent (Table
3, entries 3 and 4). Moreover, when R1 is a strongly electron-
deficient aromatic ring such as para-NO2C6H4, no desired
product was observed, presumably due to the electronic effect.
Upon changing R1 to heteroaromatic groups (R1 = 2-furan, 2-
thiophene) or a sterically bulky 2-naphthalene moiety, the
reactions also proceeded efficiently to afford the corresponding
products 6l−6n in 87−90% yields with good diastereoselectiv-
ities and 90% ee values (Table 3, entries 11−13). Replacing the
aromatic group with a cyclopropyl group provided the
corresponding product 6o in 83% yield along with >20:1 dr
and 96% ee value (Table 3, entry 14). The other β,γ-
unsaturated α-keto esters such as isopropyl, tert-butyl, or benzyl
esters are also suitable substrates for this asymmetric [3+2]
cycloaddition, giving the corresponding products 6p−6r in 71−
87% yields along with 13:1 to >20:1 dr and 87−94% ee values
(Table 3, entries 15−17).
Table 1. Screening of Solvents and Concentration for Pel-
Catalyzed [3+2] Cycloaddition
a
b
c
d
entry
solvent
yield [%]
dr
ee [%]
1a
2
toluene
THF
67
72
64
49
70
88
75
93
13:1
11:1
4:1
92
90
68
51
80
74
80
92
3
CH3CN
DCM
4
5:1
5
DMF
3:1
6
DMSO
Et2O
2:1
7
3:1
e
8
toluene
19:1
a
The reaction was conducted with 1a (0.1 mmol) and 5a (0.15 mmol)
b
c
in solvent (1.0 mL). Isolated yield. The diastereomeric ratios were
d
determined by 1H NMR spectroscopy. The ee values were
e
determined by chiral HPLC on Chiralcel IC. The reaction was
To illustrate the generality of the Pd(0)/L1 catalytic system,
the other activated olefin 7 and vinyl cyclopropane 1b were
conducted with 1a (0.1 mmol) and 5a (0.15 mmol) in solvent (0.5
mL).
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Table 2. Optimization of Ligand for Pd-Catalyzed Asymmetric Formal [3+2] Cycloaddition
a
b
c
d
entry
ligand
yield [%]
dr
ee [%]
1
2
3
4
5
6
L2
L3
L4
L5
L6
L7
26
77
31
23
34
93
2:1
10:1
2:1
77
−90
−78
−69
−50
7
2:1
1:1
2:1
a
b
c
The reaction was conducted with 1a (0.1 mmol) and 5a (0.15 mmol) in solvent (0.5 mL). Isolated yield. The diastereomeric ratios were
d
1
determined by H NMR spectroscopy. The ee values were determined by chiral HPLC on Chiralcel IC.
Table 3. Substrate Scope for Pd/L1-Catalyzed Asymmetric
Formal [3+2] Cycloaddition
The product 6q could be easily converted into compound 9
through hydrolysis and condensation with 4-bromobenzyl-
amine in 51% yield after two steps along with a 94% ee value as
well as >20:1 dr value (Scheme 3). X-ray diffraction analysis of
compound 9 showed that its absolute configuration is 2S, 3S,
4R, which is consistent with 8a and 8b. Accordingly, the
product 6q has the 2S, 3S, 4R absolute configuration. With the
same sign of the optical rotation of products 6a−6p and 6r as
that of 6q, we concluded that products 6a−6r also have the 2S,
3S, 4R absolute configuration. However, since the minor
diastereoisomer of 6 cannot be separated by silica gel column
chromatography, its absolute configuration is unable to be
determined at the present stage. The ORTEP drawings of 9
together with the CIF data are summarized in the Supporting
Information.10
To explain the observed stereoselectivity, we tentatively
propose a mechanistic model in Scheme 4 based on the
previous mechanistic studies by Tsuji2e and Trost.2g First, an
activated zwitterionic (π-allyl) palladium intermediate, 10, is
initially associated through ring-opening of vinylcyclopropane 1
in the presence of a chiral imidazoline−phosphine (L1)−
palladium(II) complex during the reaction. Then, attack of
malonate anion onto the β,γ-unsaturated α-keto ester provides
another (π-allyl) palladium complex, 11. Finally, the observed
major diastereomer 6a was obtained by the attack of the carbon
anion of the α-keto ester to the backside of the in situ
generated (π-allyl) palladium complex 11.
In summary, an efficient palladium-catalyzed diastereo- and
enantioselective formal [3+2] cycloaddition reaction of vinyl
cyclopropanes with β,γ-unsaturated α-keto esters has been
developed, affording functionalized cyclopentanes containing
multiple stereocenters in good to excellent yields with good to
excellent diastereo- and enantioselectivities under mild
conditions in the presence of chiral imidazoline−phosphine
ligand (aS,S,S)-L1. This newly developed chiral ligand is crucial
for this reaction. A reversal of enantioselectivity was also
observed in this reaction when ligand (aR,R,R)-L3 was used
instead of L1. Further investigations on the substrate scope as
well as the applications of the protocol are in progress.
a
b
c
d
entry
R1
R2
yield [%]
dr
ee [%]
1
4-MeC6H4, 5b
4-MeOC6H4, 5c
4-BrC6H4, 5d
4-CIC6H4, 5e
4-NO2C6H4, 5f
2-MeOC6H4, 5g
3-MeOC6H4, 5h
3-MeC6H4, 5i
2,5-(MeO)2C6H3, 5j
3,4,5-(MeO)3C6H2, 5k
2-thiophene, 51
2-furyl, 5m
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
iPr
tBu
Bn
6b, 95
6c, 96
6d, 52
6e, 61
6f, 0
>20:1
>20:1
16:1
94
94
88
82
n.d.
98
92
90
98
90
90
90
90
96
87
94
92
2
3
4
>20:1
n.d.
5
6
6g, 96
6h, 86
6i, 97
6j, 90
6k, 88
61,90
>20:1
17:1
7
8
>20:1
>20:1
14:1
9
10
11
12
13
14
15
16
17
>20:1
10:1
6m, 90
6n, 87
6o, 83
6p, 87
6q, 86
6r, 71
2-naphthyl, 5n
cyclopropyl, 5o
C6H5, 5p
>20:1
>20:1
17:1
C6H5, 5q
>20:1
13:1
C6H5, 5r
a
The reaction was conducted with 1a (0.1 mmol) and 5 (0.15 mmol)
b
c
in solvent (0.5 mL). Isolated yield. The diastereomeric ratios were
d
determined by 1H NMR spectroscopy. The ee values were
determined by chiral HPLC on Chiralcel IC.
used as the substrates and examined under the standard
conditions, respectively (Scheme 2). Notably, the desired
products 8a and 8b were also obtained in 72% and 94% yields,
16:1 and >20:1 dr values, and 97% and 82% ee values.
Moreover, the absolute configurations of 8a and 8b have been
assigned by their X-ray diffraction as 2S, 3S, 4R. The ORTEP
drawings of 8a and 8b together with their CIF data are
summarized in the Supporting Information.10
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Scheme 2. Pd/L1-Catalyzed Asymmetric [3+2] Cycloaddition of ther Vinyl Cyclopropanes and Electron-Deficient Olefins
Scheme 3. Transformation of the Cycloadduct for X-ray Crystallographic Analysis
Scheme 4. Proposed Mechanistic Model
Ligands L1−L58a and L6/L79b were prepared according to the
EXPERIMENTAL SECTION
■
previously reported procedures.
Vinyl cyclopropanes 1a6a and 1b2h were prepared according to the
General Remarks. Melting point was obtained with a Yanagimoto
micro melting point apparatus and is uncorrected. Optical rotations
previously reported procedures.
β,γ-Unsaturated α-keto esters 5a−5e,11 5f,12 5h,13 5l,14 5m,12 5n,13
were determined in a solution of CHCl3 or CH2Cl2 at 20 °C by using a
5p,15 and 5r16 were prepared according to the previously reported
Perkin-Elmer-241 MC polarimeter; [α]D values are given in units of
10−1 deg cm2 g−1. Infrared spectra were measured on a spectrometer.
procedures.
1H NMR spectra were recorded for a solution in CDCl3 with
General Procedure for the Synthesis of β,γ-Unsaturated α-
tetramethylsilane (TMS) as internal standard; 31P NMR spectra were
recorded for a solution in CDCl3 with 85% H3PO4 as the external
reference. J values are in Hz. Mass spectra were recorded with a HP-
5989 instrument, and HRMS was measured by a Finnigan MA+ mass
spectrometer. Organic solvents used were dried by standard methods
when necessary. Commercially obtained reagents were used without
further purification. All reactions were monitored by TLC with
Huanghai GF254 silica gel coated plates. Flash column chromatography
was carried out using 300−400 mesh silica gel at increased pressure.
All reactions were performed under argon using standard Schlenk
techniques. The optical purities of products were determined by
HPLC analysis using a Shimadzu SPD-10A vp series with chiral
columns (Chiralpak AD-H, OD-H, and IC-H columns 4.6 × 250 mm,
Daicel Chemical Ind., Ltd.), and the absolute configuration of the
major enantiomer was assigned according to the sign of the specific
rotation.
Keto Esters 5. To the appropriate aldehyde (1.0 equiv) solution in
methanol was added pyruvic acid (1.0 equiv), and the mixture was
cooled to 10 °C under an atmosphere of nitrogen. To this was added a
solution of KOH (1.5 equiv) in methanol dropwise at 15−20 °C. After
the addition of two-thirds of the alkali, the rest of the alkali was added
in one part before precipitation of potassium pyruvate could occur.
Then the ice bath was removed, and the temperature of the reaction
mixture increased from 20 °C to 35−40 °C. The reaction mixture was
stirred at this temperature for 3 h and then maintained at 10 °C for 10
h. The precipitate was filtered on a Buchner funnel under suction and
washed with chilled methanol followed by diethyl ether to afford
potassium 4-aryl-2-oxobut-3-enoate (4-cyclopropyl-2-oxobut-3-
enoate) as a yellow solid.
Acetyl chloride (10 mL) was added dropwise to the corresponding
alcohol (70 mL) cooled in an ice bath to produce dry hydrochloric
acid. Potassium 4-aryl-2-oxobut-3-enoate (4-cyclopropyl-2-oxobut-3-
enoate) (10 mmol) was added at 0 °C. The reaction was warmed to
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room temperature, stirred for 2 h, and then refluxed for 6 h. The
solvent was removed by evaporation. Water (15 mL) was added to the
crude product, which was then extracted with CH2Cl2 (18 mL × 2).
The combined organic phase was washed with NaHCO3 (10 mL × 2)
and then with water (10 mL). After the organic layer was separated
and dried over Na2SO4.The crude product was purified by flash silica
gel chromatography to afford products 5g, 5i−5k, 5o, and 5q.
(E)-Ethyl 4-(2-methoxyphenyl)-2-oxobut-3-enoate, 5g: 10.0
7.44 (m, 3H, ArH), 7.59−7.63 (m, 2H, ArH), 7.79 (d, J = 16.5 Hz, 1H,
CH). 13C NMR (CDCl3, 75 MHz, TMS): δ 27.8, 84.0, 120.7, 128.9,
129.0, 131.4, 134.0, 147.9, 161.7, 184.0. IR (CH2Cl2): ν 2981, 2932,
1721, 1693, 1666, 1605, 1578, 1479, 1450, 1370, 1259, 1135, 1078,
982, 941, 839, 776, 742, 689 cm−1. MS (ESI) m/z (%): 255.1 (100)
[M++Na]. HRMS (ESI): calcd for C14H16O3 requires 232.1099, found
232.1090.
General Procedure for Palladium-Catalyzed Asymmetric
Formal [3+2] Cycloaddition of Vinylcyclopropane with the
Electron-Deficient Olefins in the Presence of Pd2dba3 and
Chiral Imidazoline−Phosphine Ligand L1. A solution of
enantiomerically pure ligand L1 (0.01 mmol, 10 mol %) and
palladium dibenzylideneacetone Pd2dba3 (0.005 mmol, 5 mol %) in
toluene (0.25 mL) was stirred at room temperature under an argon
atmosphere for 30 min. To the solution was added a solution of
dimethyl 2-vinylcyclopropane-1,1-dicarboxylate (1a; 0.1 mmol, 1
equiv) and (E)-ethyl 2-oxo-4-phenylbut-3-enoate (5a, 0.15 mmol,
1.5 equiv) in toluene (0.25 mL), and the reaction was stirred at room
temperature for 24 h. The mixture was concentrated in vacuo to yield
the crude product, which was purified by flash chromatography on
silica gel (eluent: PE/EtOAc, 10:1to 20:1) to furnish the desired
cyclopentane 6a as a colorless oil.
1
mmol scale, yellow oil, 66% yield (1.54 g). H NMR (CDCl3, 300
MHz, TMS): δ 1.42 (t, J = 7.2 Hz, 3H, CH3), 3.91 (s, 3H, CH3), 4.40
(q, J = 7.2 Hz, 2H, CH2), 6.92−7.02 (m, 2H, ArH), 7.38−7.45 (m,
2H, ArH, CH), 7.63 (d, J = 7.8 Hz, 1H, ArH), 8.20 (d, J = 16.5 Hz,
1H, CH). 13C NMR (CDCl3, 75 MHz, TMS): δ 14.0, 55.5, 62.3,
111.2, 120.8, 120.9, 122.9, 129.4, 133.0, 143.9, 159.2, 162.6, 183.5. IR
(CH2Cl2) ν 2955, 2933, 1725, 1688, 1660, 1594, 1570, 1488, 1465,
1244, 1143, 1107, 1077, 1049, 1022, 857, 801, 752 cm−1. MS (EI) m/z
(%): 63 (4.16), 77 (9.65), 89 (6.43), 105 (14.07), 118 (12.09), 161
(100.00), 162 (11.24), 234 (6.56). HRMS (EI): calcd for C13H14O4
requires 234.0892, found 234.0889.
(E)-Ethyl 2-oxo-4-m-tolylbut-3-enoate, 5i: 10.0 mmol scale,
1
yellow oil, 72% yield (1.56 g). H NMR (CDCl3, 400 MHz, TMS): δ
1.42 (t, J = 7.2 Hz, 3H, CH3), 2.40 (s, 3H, CH3), 4.40 (q, J = 7.2 Hz,
2H, CH2), 7.28−7.38 (m, 3H, ArH, CH), 7.44 (d, J = 7.2 Hz, 2H,
ArH), 7.84 (d, J = 16.4 Hz, 1H, CH). 13C NMR (CDCl3, 100 MHz,
TMS): δ 14.0, 21.1, 62.3, 120.2, 126.2, 128.9, 129.5, 132.4, 133.9,
138.7, 148.5, 162.2, 182.8. IR (CH2Cl2) ν 2960, 2927, 1723, 1693,
1664, 1560, 1582, 1447, 1370, 1263, 1140, 1107, 1075, 1015, 986, 857,
768, 700 cm−1. MS (EI) m/z (%): 145 (100.00), 115 (30.02), 149
(23.10), 117 (19.58), 91 (12.01), 146 (11.57), 218 (10.80), 116
(6.39). HRMS (EI): calcd for C13H14O3 requires 218.0943, found
218.0941.
(E)-eEthyl 4-(2,5-dimethoxyphenyl)-2-oxobut-3-enoate, 5j:
10.0 mmol scale, yellow oil, 62% yield (1.64 g). 1H NMR (CDCl3, 300
MHz, TMS): δ 1.42 (t, J = 7.5 Hz, 3H, CH3), 3.81 (s, 3H, CH3), 3.87
(s, 3H, CH3), 4.40 (q, J = 7.5 Hz, 2H, CH2), 6.87 (d, J = 9.3 Hz, 1H,
ArH), 6.99 (dd, J = 3.3 Hz, 9.3 Hz, 1H, ArH), 7.13 (d, J = 3.3 Hz, 1H,
ArH), 7.37 (d, J = 16.2 Hz, 1H, CH), 8.19 (d, J = 16.2 Hz, 1H, 
CH). 13C NMR (CDCl3, 75 MHz, TMS): δ 14.0, 55.7, 56.0, 62.3,
112.5, 113.0, 119.1, 120.9, 123.3, 143.6, 153.4, 153.7, 162.5, 183.3. IR
(CH2Cl2): ν 2955, 2925, 1726, 1687, 1659, 1593, 1494, 1465, 1429,
1281, 1221, 1141, 1076, 1042, 1019, 848, 808, 740, 700 cm−1. MS (EI)
m/z (%): 191 (100.00), 176 (46.02), 264 (19.23), 192 (13.07), 148
(10.91), 161 (9.96), 133 (8.26), 77 (6.51). HRMS (EI): calcd for
C14H16O5 requires 264.0998, found 264.1002.
(E)-Ethyl 2-oxo-4-(3,4,5-trimethoxyphenyl)but-3-enoate, 5k:
10.0 mmol scale, yellow oil, 56% yield (1.65 g). 1H NMR (CDCl3, 300
MHz, TMS): δ 1.43 (t, J = 7.2 Hz, 3H, CH3), 3.91 (s, 9H, CH3), 4.41
(q, J = 7.2 Hz, 2H, CH2), 6.87 (s, 2H, ArH), 7.29 (d, J = 16.2 Hz, 1H,
CH), 7.81 (d, J = 16.2 Hz, 1H, CH). 13C NMR (CDCl3, 75
MHz, TMS): δ 14.0, 56.1, 60.9, 62.5, 106.2, 119.5, 129.3, 141.3, 148.4,
153.4, 162.3, 182.4. IR (CH2Cl2): ν 2954, 2924, 1722, 1689, 1588,
1498, 1460, 1421, 1328, 1241, 1124, 1069, 1008, 840, 807, 781, 738
cm−1. MS (EI) m/z (%): 221 (100.00), 294 (20.81), 190 (14.40), 191
(14.32), 222 (13.87), 163 (7.92), 193 (7.30), 161 (6.70). HRMS (EI):
calcd for C15H18O6 requires 294.1103, found 294.1101.
(2S,3S,4R)-Dimethyl 3-(2-ethoxy-2-oxoacetyl)-2-phenyl-4-vi-
nylcyclopentane-1,1-dicarboxylate, 6a: colorless oil, 93% yield
(36 mg). The ee was determined by chiral HPLC (Daicel
CHIRALPACK IC-H, hexane/iPrOH, 95:5, 0.7 mL/min, 214 nm).
Main product: tmajor = 54.3 min, tminor = 44.7 min. [α]20 = −22.8 (c
D
0.50, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): δ 1.31 (t, J = 6.9
Hz, 3H, CH3), 2.07 (dd, J = 4.8 Hz, 14.1 Hz, 1H, CH2), 3.05 (dd, J =
7.5 Hz, 14.1 Hz, 1H, CH2), 3.22 (s, 3H, CH3), 3.62−3.71 (m, 1H,
CH), 3.74 (s, 3H, CH3), 4.25 (q, J = 6.9 Hz, 2H, CH2), 4.47 (dd, J =
8.7 Hz, 11.1 Hz, 1H, CH), 4.62 (d, J = 11.1 Hz, 1H, CH), 5.01 (d, J =
9.6 Hz, 1H, CH2), 5.05 (d, J = 16.8 Hz, 1H, CH2), 5.54−5.67 (m,
1H, CH), 7.18−7.30 (m, 5H, ArH). 13C NMR (CDCl3, 75 MHz,
TMS): δ 13.8, 40.9, 44.7, 49.9, 52.1, 52.7, 55.9, 62.4, 64.3, 117.5, 127.3,
128.0, 128.4, 136.9, 137.6, 160.4, 171.0, 171.9, 192.5. IR (CH2Cl2): ν
2953, 2911, 1721, 1496, 1434, 1253, 1211, 1171, 1092, 1070, 922, 811,
750, 700, 667 cm−1. MS (ESI) m/z (%): 411.3 (100) [M+ + Na].
HRMS (MALDI): calcd for C21H24O7Na+ (M+ + Na) requires
411.1424, found 411.1414.
(2S,3S,4R)-Dimethyl 3-(2-ethoxy-2-oxoacetyl)-2-p-tolyl-4-vi-
nylcyclopentane-1,1-dicarboxylate, 6b: colorless oil, 95% yield
(38 mg). The ee was determined by chiral HPLC (Daicel
CHIRALPACK IC-H, hexane/iPrOH, 95:5, 1.0 mL/min, 214 nm).
Main product: tmajor = 58.9 min, tminor = 28.0 min. [α]20 = −16.9 (c
D
1.35, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): δ 1.30 (t, J = 6.9
Hz, 3H, CH3), 2.04 (dd, J = 4.8 Hz, 14.1 Hz, 1H, CH2), 2.27 (s, 3H,
CH3), 3.02 (dd, J = 7.8 Hz, 14.1 Hz, 1H, CH2), 3.27 (s, 3H, CH3),
3.61−3.70 (m, 1H, CH), 3.73 (s, 3H, CH3), 4.24 (q, J = 6.9 Hz, 2H,
CH2), 4.46 (dd, J = 8.1 Hz, 11.7 Hz, 1H, CH), 4.56 (d, J = 11.7 Hz,
1H, CH), 5.00 (d, J = 10.2 Hz, 1H, CH2), 5.05 (d, J = 17.4 Hz, 1H,
CH2), 5.52−5.65 (m, 1H, CH), 7.05 (d, J = 7.8 Hz, 2H, ArH),
7.16 (d, J = 7.8 Hz, 2H, ArH). 13C NMR (CDCl3, 75 MHz, TMS): δ
13.8, 20.9, 40.9, 44.6, 49.7, 52.1, 52.6, 55.8, 62.3, 64.2, 117.4, 128.3,
128.7, 134.4, 136.8, 137.1, 160.4, 171.1, 171.9, 192.6. IR (CH2Cl2): ν
3081, 2976, 2914, 2953, 1517, 1435, 1254, 1212, 1176, 1092, 1070,
925, 839, 716 cm−1. MS (ESI) m/z (%): 425.2 (100) [M+ + Na].
HRMS (MALDI): calcd for C22H26O7Na+ (M+ + Na) requires
425.1578, found 425.1571.
(E)-Ethyl 4-cyclopropyl-2-oxobut-3-enoate, 5o: 10.0 mmol
1
scale, yellow oil, 56% yield (940 mg). H NMR (CDCl3, 300 MHz,
TMS): δ 0.77−0.83 (m, 2H, CH2), 1.07−1.14 (m, 2H, CH2), 1.38 (t, J
= 7.5 Hz, 3H, CH3), 1.63−1.76 (m, 1H, CH), 4.34 (q, J = 7.5 Hz, 2H,
CH2), 6.66 (dd, J = 10.2 Hz, 15.3 Hz, 1H, CH), 6.81 (d, J = 15.3
Hz, 1H, CH). 13C NMR (CDCl3, 75 MHz, TMS): δ 10.2, 14.0,
16.0, 62.2, 121.9, 160.4, 162.4, 182.0. IR (CH2Cl2) ν 3021, 2985, 2934,
1727, 1691, 1665, 1606, 1455, 1368, 1311, 1247, 1178, 1138, 1080,
1012, 981, 939, 896, 853, 778, 736 cm−1. MS (EI) m/z (%): 95
(100.00), 67 (63.00), 41 (20.00), 65 (12.37), 96 (7.14), 66 (5.31), 140
(4.12), 68 (3.96). HRMS (EI): calcd for C9H12O3 requires 168.0786,
found 168.0790.
(2S,3S,4R)-Dimethyl 3-(2-ethoxy-2-oxoacetyl)-2-(4-methoxy-
phenyl)-4-vinylcyclopentane-1,1-dicarboxylate, 6c: colorless oil,
96% yield (40 mg). The ee was determined by chiral HPLC (Daicel
CHIRALPACK IC-H, hexane/iPrOH, 95:5, 0.5 mL/min, 214 nm).
Main product: tmajor = 81.7 min, tminor = 49.8 min. [α]20 = −23.1 (c
D
2.05, CH2Cl2). 1H NMR (CDCl3, 400 MHz, TMS): δ 1.30 (t, J = 7.2
Hz, 3H, CH3), 2.05 (dd, J = 5.2 Hz, 14.0 Hz, 1H, CH2), 3.02 (dd, J =
7.6 Hz, 14.0 Hz, 1H, CH2), 3.28 (s, 3H, CH3), 3.61−3.70 (m, 1H,
CH), 3.73 (s, 3H, CH3), 3.75 (s, 3H, CH3), 4.25 (q, J = 7.2 Hz, 2H,
CH2), 4.43 (dd, J = 8.8 Hz, 11.6 Hz, 1H, CH), 4.55 (d, J = 11.6 Hz,
1H, CH), 5.00 (d, J = 10.4 Hz, 1H, CH2), 5.04 (d, J = 17.2 Hz, 1H,
(E)-tert-Butyl 2-oxo-4-phenylbut-3-enoate, 5q: 10.0 mmol
1
scale, yellow oil, 42% yield (974 mg). H NMR (CDCl3, 300 MHz,
TMS): δ 1.60 (s, 9H, CH3), 7.28 (d, J = 16.5 Hz, 1H, CH), 7.39−
7595
dx.doi.org/10.1021/om300896z | Organometallics 2012, 31, 7591−7599

Organometallics
Article
CH2), 5.54−5.64 (m, 1H, CH), 6.78 (d, J = 8.4 Hz, 2H, ArH),
7.20 (d, J = 8.4 Hz, 2H, ArH). 13C NMR (CDCl3, 100 MHz, TMS): δ
13.9, 40.9, 44.6, 49.4, 52.2, 52.7, 55.1, 55.9, 62.4, 64.2, 113.4, 117.5,
129.5, 137.1, 158.7, 160.5, 171.2, 172.0, 192.7. IR (CH2Cl2): ν 3081,
2988, 2954, 2915, 2841, 1725, 1612, 1514, 1435, 1251, 1213, 1181,
1070, 925, 843, 732 cm−1. MS (ESI) m/z (%): 419.1 (100) [M+ + 1].
HRMS (ESI): calcd for C22H26O8Na+ (M+ + Na) requires 441.1520,
found 441.1529.
7.2 Hz, 3H, CH3), 2.05 (dd, J = 5.1 Hz, 14.1 Hz, 1H, CH2), 3.05 (dd, J
= 8.1 Hz, 14.1 Hz, 1H, CH2), 3.26 (s, 3H, CH3), 3.61−3.70 (m, 1H,
CH), 3.74 (s, 3H, CH3), 3.78 (s, 3H, CH3), 4.25 (q, J = 7.2 Hz, 2H,
CH2), 4.45 (dd, J = 8.7 Hz, 11.7 Hz, 1H, CH), 4.58 (d, J = 11.7 Hz,
1H, CH), 5.00 (d, J = 9.6 Hz, 1H, CH2), 5.05 (d, J = 16.2 Hz, 1H,
CH2), 5.53−5.66 (m, 1H, CH), 6.73 (dd, J = 1.8 Hz, 7.8 Hz, 1H,
ArH), 6.83 (d, J = 7.8 Hz, 1H, ArH), 6.88 (s, 1H, ArH), 7.15 (t, J = 7.8
Hz, 1H, ArH). 13C NMR (CDCl3, 75 MHz, TMS): δ 13.8, 41.0, 44.7,
49.9, 52.2, 52.7, 55.1, 55.9, 62.4, 64.3, 112.8, 114.6, 117.5, 120.4, 128.9,
137.0, 139.2, 159.2, 160.4, 171.0, 171.9, 192.5. IR (CH2Cl2) ν 2953,
2917, 2829, 1724, 1601, 1585, 1489, 1435, 1369, 1250, 1209, 1172,
1068, 927, 861, 781, 699 cm−1. MS (ESI) m/z (%): 419.2 (100) [M+ +
1]. HRMS (MALDI): calcd for C22H26O8Na+ (M+ + Na) requires
441.1531, found 441.1520.
(2S,3S,4R)-Dimethyl 2-(4-bromophenyl)-3-(2-ethoxy-2-oxoa-
cetyl)-4-vinylcyclopentane-1,1-dicarboxylate, 6d: colorless oil,
52% yield (24 mg). The ee was determined by chiral HPLC (Daicel
CHIRALPACK IC-H, hexane/iPrOH, 97:3, 0.5 mL/min, 214 nm).
Main product: tmajor = 54.2 min, tminor = 42.0 min. [α]20 = −20.2 (c
D
1.30, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): δ 1.31 (t, J = 7.2
Hz, 3H, CH3), 2.05 (dd, J = 4.8 Hz, 14.1 Hz, 1H, CH2), 3.03 (dd, J =
7.8 Hz, 14.1 Hz, 1H, CH2), 3.30 (s, 3H, CH3), 3.61−3.70 (m, 1H,
CH), 3.74 (s, 3H, CH3), 4.25 (q, J = 7.2 Hz, 2H, CH2), 4.42 (dd, J =
8.7 Hz, 11.4 Hz, 1H, CH), 4.53 (d, J = 11.4 Hz, 1H, CH), 5.01 (d, J =
9.6 Hz, 1H, CH2), 5.05 (d, J = 15.6 Hz, 1H, CH2), 5.50−5.63 (m,
1H, CH), 7.17 (d, J = 8.4 Hz, 2H, ArH), 7.37 (d, J = 8.4 Hz, 2H,
ArH). 13C NMR (CDCl3, 75 MHz, TMS): δ 13.8, 40.9, 44.5, 49.4,
52.3, 52.8, 55.7, 62.5, 64.0, 117.8, 121.3, 130.2, 131.1, 136.6, 136.8,
160.4, 170.9, 171.7, 192.4. IR (CH2Cl2) ν 2987, 2952, 2917, 1723,
1610, 1516, 1434, 1248, 1208, 1176, 1092, 1069, 924, 899, 828 cm−1.
MS (ESI) m/z (%): 469.0 (100) [M+ + 1]. HRMS (ESI) calcd for
C21H23Br1O7Na+ (M+ + Na) requires 489.0519, found 489.0537.
(2S,3S,4R)-Dimethyl 2-(4-chlorophenyl)-3-(2-ethoxy-2-oxoa-
cetyl)-4-vinylcyclopentane-1,1-dicarboxylate, 6e: colorless oil,
61% yield (26 mg). The ee was determined by chiral HPLC (Daicel
CHIRALPACK IC-H, hexane/iPrOH, 95:5, 0.7 mL/min, 214 nm).
(2S,3S,4R)-Dimethyl 3-(2-ethoxy-2-oxoacetyl)-2-m-tolyl-4-vi-
nylcyclopentane-1,1-dicarboxylate, 6i: colorless oil, 97% yield
(39 mg). The ee was determined by chiral HPLC (Daicel
CHIRALPACK IC-H, hexane/iPrOH, 97:3, 0.7 mL/min, 214 nm).
Main product: tmajor = 85.7 min, tminor = 58.1 min. [α]20 = −51.8 (c
D
2.00, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): δ 1.30 (t, J = 6.9
Hz, 3H, CH3), 2.05 (dd, J = 5.1 Hz, 13.8 Hz, 1H, CH2), 2.30 (s, 3H,
CH3), 3.04 (dd, J = 7.5 Hz, 13.8 Hz, 1H, CH2), 3.24 (s, 3H, CH3),
3.62−3.71 (m, 1H, CH), 3.74 (s, 3H, CH3), 4.24 (q, J = 6.9 Hz, 2H,
CH2), 4.44 (dd, J = 8.4 Hz, 11.1 Hz, 1H, CH), 4.57 (d, J = 11.1 Hz,
1H, CH), 5.00 (d, J = 10.5 Hz, 1H, CH2), 5.06 (d, J = 17.1 Hz, 1H,
CH2), 5.53−5.66 (m, 1H, CH), 6.99 (d, J = 6.9 Hz, 1H, ArH),
7.03−7.15 (m, 3H, ArH). 13C NMR (CDCl3, 75 MHz, TMS): δ 13.8,
21.4, 41.0, 44.8, 49.9, 52.1, 52.7, 56.0, 62.4, 64.3, 117.5, 125.3, 127.9,
128.1, 129.3, 137.1, 137.48, 137.53, 160.5, 171.1, 171.9, 192.6. IR
(CH2Cl2): ν 3024, 2980, 2952, 2914, 2837, 1725, 1608, 1434, 1254,
1210, 1175, 1070, 928, 859, 812, 782, 703 cm−1. MS (ESI) m/z (%):
403.1 (100) [M+ + 1]. HRMS (MALDI): calcd for C22H26O7Na+ (M+
+ Na) requires 425.1569, found 425.1571.
Main product: tmajor = 23.9 min, tminor = 18.9 min. [α]20 = −19.9 (c
D
1.10, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): δ 1.31 (t, J = 6.9
Hz, 3H, CH3), 2.05 (dd, J = 4.8 Hz, 14.1 Hz, 1H, CH2), 3.03 (dd, J =
7.5 Hz, 14.1 Hz, 1H, CH2), 3.30 (s, 3H, CH3), 3.62−3.71 (m, 1H,
CH), 3.74 (s, 3H, CH3), 4.26 (q, J = 6.9 Hz, 2H, CH2), 4.43 (dd, J =
8.7 Hz, 11.7 Hz, 1H, CH), 4.55 (d, J = 11.7 Hz, 1H, CH), 5.01 (d, J =
8.7 Hz, 1H, CH2), 5.05 (d, J = 15.9 Hz, 1H, CH2), 5.50−5.63 (m,
1H, CH), 7.23 (br, 4H, ArH). 13C NMR (CDCl3, 75 MHz, TMS):
δ 13.9, 40.9, 44.5, 49.3, 52.3, 52.8, 55.8, 62.5, 64.1, 117.8, 128.2, 129.9,
133.2, 136.0, 136.8, 160.4, 170.9, 171.8, 192.4. IR (CH2Cl2): ν 2976,
2953, 2917, 2848, 1725, 1493, 1435, 1250, 1366, 1209, 1175, 1090,
1070, 1015, 925, 843, 819, 746, 717 cm−1. MS (ESI) m/z (%): 423.0
(100) [M+ + 1]. HRMS (ESI): calcd for C21H23Cl1O7Na+ (M+ + Na)
requires 445.1025, found 445.1022.
(2S,3S,4R)-Dimethyl 2-(2,5-dimethoxyphenyl)-3-(2-ethoxy-
2-oxoacetyl)-4-vinylcyclopentane-1,1-dicarboxylate, 6j: color-
less oil, 90% yield (40 mg). The ee was determined by chiral HPLC
(Daicel CHIRALPACK AD-H, hexane/iPrOH, 90:10, 1.0 mL/min,
214 nm). Main product: tmajor = 25.6 min, tminor = 21.1 min. [α]20
=
D
1
−46.6 (c 1.20, CH2Cl2). H NMR (CDCl3, 300 MHz, TMS): δ 1.30
(t, J = 6.9 Hz, 3H, CH3), 2.10 (dd, J = 6.6 Hz, 13.8 Hz, 1H, CH2), 2.96
(dd, J = 7.5 Hz, 13.8 Hz, 1H, CH2), 3.37 (s, 3H, CH3), 3.57−3.66 (m,
1H, CH), 3.70 (s, 3H, CH3), 3.74 (s, 3H, CH3), 3.75 (s, 3H, CH3),
4.23 (q, J = 6.9 Hz, 2H, CH2), 4.64 (dd, J = 9.0 Hz, 10.5 Hz, 1H, CH),
4.80 (d, J = 10.5 Hz, 1H, CH), 4.99 (d, J = 9.9 Hz, 1H, CH2), 5.07
(d, J = 16.8 Hz, 1H, CH2), 5.57−5.70 (m, 1H, CH), 6.67−6.75
(m, 2H, ArH), 6.89 (d, J = 1.8 Hz, 1H, ArH). 13C NMR (CDCl3, 75
MHz, TMS): δ 13.8, 41.1, 44.9, 46.4, 52.0, 52.6, 55.3, 55.6, 56.0, 62.3,
63.4, 111.6, 112.8, 116.8, 117.4, 127.5, 137.1, 152.3, 153.1, 160.6,
170.6, 171.7, 193.4. IR (CH2Cl2): ν 3090, 2983, 2952, 2837, 1726,
1590, 1502, 1432, 1368, 1225, 1176, 1094, 1071, 1050, 1024, 927, 860,
804, 734 cm−1. MS (MALDI) m/z (%): 471.1 (100) [M+ + Na].
HRMS (MALDI): calcd for C23H28O9Na+ (M+ + Na) requires
471.1633, found 471.1626.
(2S,3S,4R)-Dimethyl 3-(2-ethoxy-2-oxoacetyl)-2-(2-methoxy-
phenyl)-4-vinylcyclopentane-1,1-dicarboxylate, 6g: colorless
oil, 96% yield (40 mg). The ee was determined by chiral HPLC
(Daicel CHIRALPACK AD-H, hexane/iPrOH, 90:10, 1.0 mL/min,
20
214 nm). Main product: tmajor = 22.0 min, tminor = 23.6 min. [α]D
=
1
−43.2 (c 1.90, CH2Cl2). H NMR (CDCl3, 300 MHz, TMS): δ 1.29
(t, J = 6.9 Hz, 3H, CH3), 2.11 (dd, J = 6.3 Hz, 13.8 Hz, 1H, CH2), 2.97
(dd, J = 7.8 Hz, 13.8 Hz, 1H, CH2), 3.32 (s, 3H, CH3), 3.58−3.67 (m,
1H, CH), 3.70 (s, 3H, CH3), 3.79 (s, 3H, CH3), 4.23 (q, J = 6.9 Hz,
2H, CH2), 4.66 (dd, J = 9.3 Hz, 10.8 Hz, 1H, CH), 4.87 (d, J = 10.8
Hz, 1H, CH), 4.99 (d, J = 10.2 Hz, 1H, CH2), 5.07 (d, J = 14.1 Hz,
1H, CH2), 5.59−5.72 (m, 1H, CH), 6.79 (d, J = 7.5 Hz, 1H,
ArH), 6.86 (t, J = 7.5 Hz, 1H, ArH), 7.17 (dt, J = 1.5 Hz, 7.5 Hz, 1H,
ArH), 7.29 (d, J = 7.5 Hz, 1H, ArH). 13C NMR (CDCl3, 75 MHz,
TMS): δ 13.8, 41.1, 45.3, 46.3, 51.9, 52.6, 55.2, 55.4, 62.2, 63.4, 110.5,
117.4, 120.3, 126.4, 128.4, 130.7, 137.1, 158.0, 160.1, 170.7, 171.8,
193.4. IR (CH2Cl2) ν 2987, 2952, 2921, 2833, 1726, 1601, 1495, 1461,
1434, 1245, 1174, 1071, 1027, 927, 858, 755 cm−1. MS (ESI) m/z (%):
419.2 (100) [M+ + 1]. HRMS (MALDI): calcd for C22H26 O8Na+ (M+
+ Na) requires 441.1524, found 441.1520.
(2S,3S,4R)-Dimethyl 3-(2-ethoxy-2-oxoacetyl)-2-(3,4,5-trime-
thoxyphenyl)-4-vinylcyclopentane-1,1-dicarboxylate, 6k: color-
less oil, 88% yield (42 mg). The ee was determined by chiral HPLC
(Daicel CHIRALPACK AD-H, hexane/iPrOH, 90:10, 0.7 mL/min,
230 nm). Main product: tmajor = 52.2 min, tminor = 33.8 min. [α]20
=
D
1
−41.3 (c 2.00, CH2Cl2). H NMR (CDCl3, 300 MHz, TMS): δ 1.32
(t, J = 6.9 Hz, 3H, CH3), 2.07 (dd, J = 4.2 Hz, 14.1 Hz, 1H, CH2), 3.07
(dd, J = 7.5 Hz, 14.1 Hz, 1H, CH2), 3.30 (s, 3H, CH3), 3.59−3.68 (m,
1H, CH), 3.75 (s, 3H, CH3), 3.78 (s, 3H, CH3), 3.84 (s, 6H, CH3),
4.27 (q, J = 6.9 Hz, 2H, CH2), 4.43 (dd, J = 8.1 Hz, 11.7 Hz, 1H, CH),
4.55 (d, J = 11.7 Hz, 1H, CH), 5.01 (d, J = 5.4 Hz, 1H, CH2), 5.05
(d, J = 11.7 Hz, 1H, CH2), 5.53−5.66 (m, 1H, CH), 6.53 (d, J =
5.7 Hz, 2H, ArH). 13C NMR (CDCl3, 75 MHz, TMS): δ 13.8, 40.9,
44.6, 50.2, 52.3, 52.7, 55.99, 56.01, 60.7, 62.5, 64.1, 105.5, 117.5, 133.2,
136.9, 137.1, 152.6, 160.6, 171.1, 172.0, 192.5. IR (CH2Cl2): ν 2955,
2924, 2853, 1725, 1589, 1509, 1461, 1244, 1208, 1125, 1094, 1071,
924, 848, 803, 701 cm−1. MS (ESI) m/z (%): 479.1 (100) [M+ + 1].
(2S,3S,4R)-Dimethyl 3-(2-ethoxy-2-oxoacetyl)-2-(3-methoxy-
phenyl)-4-vinylcyclopentane-1,1-dicarboxylate, 6h: colorless
oil, 86% yield (36 mg). The ee was determined by chiral HPLC
(Daicel CHIRALPACK PC-2, hexane/iPrOH, 90:10, 0.5 mL/min, 230
nm). Main product: tmajor = 39.1 min, tminor = 48.3 min. [α]20D = −48.5
1
(c 1.65, CH2Cl2). H NMR (CDCl3, 300 MHz, TMS): δ 1.31 (t, J =
7596
dx.doi.org/10.1021/om300896z | Organometallics 2012, 31, 7591−7599

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HRMS (MALDI): calcd for C24H30O10Na+ (M+ + Na) requires
501.1718, found 501.1731.
MHz, TMS): δ 4.0, 4.2, 12.4, 13.9, 41.1, 45.2, 50.7, 52.3, 52.6, 56.3,
62.4, 63.0, 117.3, 136.7, 160.8, 171.6, 172.1, 194.1. IR (CH2Cl2): ν
2991, 2954, 2859, 1724, 1640, 1434, 1251, 1178, 1072, 1023, 924, 859,
804, 726 cm−1. MS (ESI) m/z (%): 353.2 (100) [M+ + 1]. HRMS
(MALDI): calcd for C18H24O7Na+ (M+ + Na) requires 375.1422,
found 375.1414.
(2S,3S,4R)-Dimethyl 3-(2-ethoxy-2-oxoacetyl)-2-(thiophen-
2-yl)-4-vinylcyclopentane-1,1-dicarboxylate, 6l: colorless oil,
90% yield (35 mg). The ee was determined by chiral HPLC (Daicel
CHIRALPACK AD-H, hexane/iPrOH, 80:20, 0.5 mL/min, 230 nm).
Main product: tmajor = 28.1 min, tminor = 42.6 min. [α]20 = −41.5 (c
(2S,3S,4R)-Dimethyl 3-(2-isopropoxy-2-oxoacetyl)-2-phenyl-
4-vinylcyclopentane-1,1-dicarboxylate, 6p: colorless oil, 87%
yield (35 mg). The ee was determined by chiral HPLC (Daicel
CHIRALPACK IC-H, hexane/iPrOH, 97:3, 0.7 mL/min, 214 nm).
D
1.60, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): δ 1.33 (t, J = 7.2
Hz, 3H, CH3), 2.03 (dd, J = 5.7 Hz, 14.1 Hz, 1H, CH2), 2.99 (dd, J =
7.8 Hz, 14.1 Hz, 1H, CH2), 3.38 (s, 3H, CH3), 3.63−3.69 (m, 1H,
CH), 3.78 (s, 3H, CH3), 4.28 (q, J = 7.2 Hz, 2H, CH2), 4.49 (dd, J =
9.0 Hz, 11.7 Hz, 1H, CH), 4.79 (d, J = 11.7 Hz, 1H, CH), 5.01 (d, J =
9.6 Hz, 1H, CH2), 5.05 (d, J = 16.2 Hz, 1H, CH2), 5.48−5.60 (m,
1H, CH), 6.87 (dd, J = 3.3 Hz, 4.8 Hz, 1H, ArH), 6.93 (d, J = 3.3
Hz, 1H, ArH), 7.12 (dd, J = 1.2 Hz, 4.8 Hz, 1H, ArH). 13C NMR
(CDCl3, 75 MHz, TMS): δ 13.8, 40.6, 44.0, 45.5, 52.4, 52.7, 56.7, 62.5,
64.2, 117.6, 124.3, 125.8, 126.4, 136.9, 140.2, 160.2, 170.8, 171.4,
192.1. IR (CH2Cl2): ν 2980, 2953, 2914, 1723, 1640, 1434, 1253,
1205, 1177, 1092, 1067, 924, 856, 700 cm−1. MS (ESI) m/z (%): 395.0
(100) [M+ + 1]. HRMS (ESI): calcd for C19H22S1O7Na+ (M+ + Na)
requires 417.0978, found 417.0987.
Main product: tmajor = 57.8 min, tminor = 45.8 min. [α]20 = −44.6 (c
D
1.65, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): δ 1.27 (d, J = 1.5
Hz, 3H, CH3), 1.29 (d, J = 1.5 Hz, 3H, CH3), 2.06 (dd, J = 5.1 Hz,
14.1 Hz, 1H, CH2), 3.05 (dd, J = 7.8 Hz, 14.1 Hz, 1H, CH2), 3.22 (s,
3H, CH3), 3.62−3.70 (m, 1H, CH), 3.74 (s, 3H, CH3), 4.47 (dd, J =
8.7 Hz, 11.7 Hz, 1H, CH), 4.62 (d, J = 11.7 Hz, 1H, CH), 4.99−5.11
(m, 3H, CH2, CH), 5.54−5.67 (m, 1H, CH), 7.17−7.31 (m, 5H,
ArH). 13C NMR (CDCl3, 75 MHz, TMS): δ 21.37, 21.40, 40.9, 44.8,
49.9, 52.1, 52.7, 55.9, 64.4, 70.5, 117.5, 127.2, 128.0, 128.5, 137.0,
137.7, 160.1, 171.0, 171.9, 192.8. IR (CH2Cl2): ν 3082, 3024, 2983,
2953, 1724, 1455, 1435, 1254, 1210, 1177, 1093, 1068, 927, 837, 700
cm−1. MS (ESI) m/z (%): 425.1 (100) [M+ + Na]. HRMS (ESI):
calcd for C22H26O7Na+ (M+ + Na) requires 425.1571, found 425.1556.
(2S,3S,4R)-Dimethyl 3-(2-tert-butoxy-2-oxoacetyl)-2-phenyl-
4-vinylcyclopentane-1,1-dicarboxylate, 6q: colorless oil, 86%
yield (36 mg). The ee was determined by chiral HPLC (Daicel
CHIRALPACK IC-H, hexane/iPrOH, 95:5, 0.7 mL/min, 214 nm).
(2S,3S,4R)-Dimethyl 3-(2-ethoxy-2-oxoacetyl)-2-(furan-2-yl)-
4-vinylcyclopentane-1,1-dicarboxylate, 6m: colorless oil, 90%
yield (34 mg). The ee was determined by chiral HPLC (Daicel
CHIRALPACK IC-H, hexane/iPrOH, 95:5, 1.0 mL/min, 214 nm).
Main product: tmajor = 64.8 min, tminor = 73.6 min. [α]20 = −7.5 (c
D
1.25, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): δ 1.33 (t, J = 6.9
Hz, 3H, CH3), 1.95 (dd, J = 6.0 Hz, 13.8 Hz, 1H, CH2), 2.95 (dd, J =
7.5 Hz, 13.8 Hz, 1H, CH2), 3.47 (s, 3H, CH3), 3.61−3.73 (m, 1H,
CH), 3.76 (s, 3H, CH3), 4.28 (q, J = 6.9 Hz, 2H, CH2), 4.46 (dd, J =
9.6 Hz, 11.4 Hz, 1H, CH), 4.63 (d, J = 11.4 Hz, 1H, CH), 5.00 (d, J =
10.2 Hz, 1H, CH2), 5.06 (d, J = 17.1 Hz, 1H, CH2), 5.46−5.59
(m, 1H, CH), 6.25 (d, J = 2.1 Hz, 2H, ArH), 7.25 (br, 1H, ArH).
13C NMR (CDCl3, 75 MHz, TMS): δ 13.9, 40.4, 44.2, 44.3, 52.8, 53.4,
Main product: tmajor = 33.0 min, tminor = 27.3 min. [α]20 = −41.9 (c
D
1
1.70, CH2Cl2). H NMR (CDCl3, 300 MHz, TMS): δ 1.48 (s, 9H,
CH3), 2.05 (dd, J = 4.8 Hz, 14.1 Hz, 1H, CH2), 3.03 (dd, J = 7.5 Hz,
14.1 Hz, 1H, CH2), 3.21 (s, 3H, CH3), 3.60−3.69 (m, 1H, CH), 3.74
(s, 3H, CH3), 4.43 (dd, J = 8.7 Hz, 11.1 Hz, 1H, CH), 4.60 (d, J = 11.1
Hz, 1H, CH), 5.02 (d, J = 11.4 Hz, 1H, CH2), 5.07 (d, J = 18.0 Hz,
1H, CH2), 5.55−5.68 (m, 1H, CH), 7.18−7.30 (m, 5H, ArH).
13C NMR (CDCl3, 75 MHz, TMS): δ 27.6, 40.9, 44.8, 50.0, 52.0, 52.7,
55.8, 64.4, 83.7, 117.3, 127.2, 128.0, 128.5, 137.1, 137.8, 159.8, 171.0,
171.9, 193.4. IR (CH2Cl2): ν 2981, 2952, 1724, 1456, 1434, 1250,
1208, 1161, 1092, 1067, 922, 838, 746, 699 cm−1. MS (ESI) m/z (%):
439.0 (100) [M+ + Na]. HRMS (ESI): calcd for C23H28O7Na+ (M+ +
Na) requires 439.1727, found 439.1715.
53.9, 62.5, 62.9, 108.2, 110.5, 117.8, 136.9, 141.6, 151.1, 160.3, 170.7,
171.2, 192.4. IR (CH2Cl2): ν 3141, 2983, 2954, 2910, 1727, 1504,
1435, 1256, 1206, 1176, 1072, 1013, 926, 831, 741 cm−1. MS (ESI) m/
z (%): 379.0 (100) [M+ + 1]. HRMS (MALDI): calcd for
C19H22O8Na+ (M+ + Na) requires 401.1218, found 401.1207.
(2S,3S,4R)-Dimethyl 3-(2-ethoxy-2-oxoacetyl)-2-(naphtha-
len-2-yl)-4-vinylcyclopentane-1,1-dicarboxylate, 6n: colorless
oil, 87% yield (38 mg). The ee was determined by chiral HPLC
(Daicel CHIRALPACK IC-H, hexane/iPrOH, 95:5, 1.0 mL/min, 214
nm). Main product: tmajor = 60.7 min, tminor = 26.3 min. [α]20D = −27.3
(2S,3S,4R)-Dimethyl 3-(2-(benzyloxy)-2-oxoacetyl)-2-phe-
nyl-4-vinylcyclopentane-1,1-dicarboxylate, 6r: colorless oil,
71% yield (32 mg). The ee was determined by chiral HPLC (Daicel
CHIRALPACK AD-H, hexane/iPrOH, 80:20, 0.5 mL/min, 230 nm).
1
(c 0.50, CH2Cl2). H NMR (CDCl3, 400 MHz, TMS): δ 1.29 (t, J =
Main product: tmajor = 36.7 min, tminor = 43.8 min. [α]20 = −36.8 (c
D
7.2 Hz, 3H, CH3), 2.10 (dd, J = 4.8 Hz, 14.4 Hz, 1H, CH2), 3.10 (dd, J
= 8.0 Hz, 14.4 Hz, 1H, CH2), 3.13 (s, 3H, CH3), 3.70−3.78 (m, 4H,
CH3, CH), 4.23 (q, J = 7.2 Hz, 2H, CH2), 4.61 (dd, J = 8.8 Hz, 11.6
Hz, 1H, CH), 4.76 (d, J = 11.6 Hz, 1H, CH), 5.03 (d, J = 10.0 Hz, 1H,
CH2), 5.08 (d, J = 17.6 Hz, 1H, CH2), 5.59−5.68 (m, 1H, 
CH), 7.40−7.45 (m, 3H, ArH), 7.71−7.79 (m, 4H, ArH). 13C NMR
(CDCl3, 100 MHz, TMS): δ 13.9, 41.1, 44.8, 50.2, 52.2, 52.8, 56.1,
62.5, 64.4, 117.7, 125.8, 125.9, 126.9, 127.2, 127.4, 127.6, 127.9, 132.7,
133.0, 135.2, 137.1, 160.5, 171.1, 172.0, 192.6. IR (CH2Cl2): ν 3053,
2980, 2951, 2840, 1723, 1601, 1508, 1434, 1250, 1206, 1176, 1069,
925, 859, 746, 700, 655 cm−1. MS (ESI) m/z (%): 439.1 (100) [M+ +
1]. HRMS (MALDI): calcd for C25H26O7Na+ (M++Na) requires
461.1580, found 461.1571.
1.40, CH2Cl2). 1H NMR (CDCl3, 400 MHz, TMS): δ 2.04 (dd, J = 5.2
Hz, 14.0 Hz, 1H, CH2), 3.02 (dd, J = 7.6 Hz, 14.0 Hz, 1H, CH2), 3.20
(s, 3H, CH3), 3.58−3.67 (m, 1H, CH), 3.73 (s, 3H, CH3), 4.46 (dd, J
= 8.4 Hz, 11.6 Hz, 1H, CH), 4.61 (d, J = 11.6 Hz, 1H, CH), 4.87 (d, J
= 9.6 Hz, 1H, CH2), 4.90 (d, J = 6.0 Hz, 1H, CH2), 5.205 (s, 1H,
CH2), 5.208 (s, 1H, CH2), 5.49−5.60 (m, 1H, CH), 7.15−7.29 (m,
5H, ArH), 7.35 (br, 5H, ArH). 13C NMR (CDCl3, 100 MHz, TMS): δ
40.9, 44.8, 49.9, 52.1, 52.7, 56.1, 64.4, 67.9, 117.6, 127.3, 128.1, 128.5,
128.57, 128.64, 128.7, 134.4, 136.8, 137.6, 160.3, 171.0, 171.9, 192.2.
IR (CH2Cl2): ν 2952, 2924, 2853, 1725, 1497, 1455, 1434, 1252, 1210,
1175, 1093, 1067, 926, 810, 749, 698 cm−1. MS (MALDI) m/z (%):
473.0 (100) [M+ + 1]. HRMS (MALDI): calcd for C26H26O7Na+ (M+
+ Na) requires 473.1584, found 473.1571.
(2S,3S,4R)-Dimethyl 2-phenyl-3-(1H-pyrrole-1-carbonyl)-4-
vinylcyclopentane-1,1-dicarboxylate, 8a: colorless solid, 63%
yield (24 mg), mp 92−95 °C. The ee was determined by chiral
HPLC (Daicel CHIRALPACK IC-H, hexane/iPrOH, 90:10, 0.5 mL/
min, 230 nm). Main product: tmajor = 50.4 min, tminor = 19.5 min.
[α]20D = −9.9 (c 0.6, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): δ
2.19 (dd, J = 5.1 Hz, 14.1 Hz, 1H, CH2), 3.04 (dd, J = 7.2 Hz, 14.1 Hz,
1H, CH2), 3.25 (s, 3H, CH3), 3.45−3.57 (m, 1H, CH), 3.75 (s, 3H,
CH3), 4.21 (dd, J = 9.0 Hz, 10.8 Hz, 1H, CH), 4.77 (d, J = 10.8 Hz,
1H, CH), 4.91 (d, J = 17.1 Hz, 1H, CH2), 4.93 (d, J = 9.6 Hz, 1H,
CH2), 5.64−5.76 (m, 1H, CH), 6.25 (br, 2H, ArH), 7.16−7.33
(m, 7H, ArH). 13C NMR (CDCl3, 75 MHz, TMS): δ 40.8, 45.3, 51.3,
(2S,3S,4R)-Dimethyl 2-cyclopropyl-3-(2-ethoxy-2-oxoace-
tyl)-4-vinylcyclopentane-1,1-dicarboxylate, 6o: colorless oil,
83% yield (29 mg). The ee was determined by chiral HPLC (Daicel
CHIRALPACK IC-H, hexane/iPrOH, 97:3, 1.0 mL/min, 214 nm).
Main product: tmajor = 25.8 min, tminor = 32.0 min. [α]20 = −10.7 (c
D
1
1.00, CH2Cl2). H NMR (CDCl3, 300 MHz, TMS): δ 0.25−0.29 (m,
1H, CH2), 0.34−0.42 (m, 3H, CH2), 0.64−0.72 (m, 1H, CH), 1.35 (t,
J = 6.9 Hz, 3H, CH3), 2.07 (dd, J = 7.5 Hz, 13.2 Hz, 1H, CH2), 2.64−
2.75 (m, 2H, CH, CH2), 3.36−3.48 (m, 1H, CH), 3.75 (s, 3H, CH3),
3.76 (s, 3H, CH3), 3.98 (dd, J = 8.7 Hz, 9.3 Hz, 1H, CH), 4.29 (q, J =
6.9 Hz, 2H, CH2), 4.96 (d, J = 9.9 Hz, 1H, CH2), 5.02 (d, J = 16.8
Hz, 1H, CH2), 5.42−5.55 (m, 1H, CH). 13C NMR (CDCl3, 75
7597
dx.doi.org/10.1021/om300896z | Organometallics 2012, 31, 7591−7599

Organometallics
Article
52.2, 52.5, 52.7, 64.2, 113.1, 117.2, 118.9, 127.4, 128.2, 128.3, 136.5,
137.4, 168.6, 171.5, 171.7. IR (CH2Cl2): ν 3156, 3079, 2951, 2914,
1724, 1603, 1468, 1434, 1266, 1210, 1178, 1105, 1075, 921, 891, 744,
700, 663−1. MS (ESI) m/z (%): 382.1 (100) [M+ + 1]. HRMS (ESI):
calcd for C22H23N1O5Na+ (M+ + Na) requires 404.1468, found
404.1465.
(CCDC 895309). This material is available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: Mshi@mail.sioc.ac.cn. Fax 86-21-64166128.
■
Ethyl 2-((1S,2S,5R)-3,3-dicyano-2-phenyl-5-vinylcyclopen-
tyl)-2-oxoacetate, 8b: white solid, 94% yield (30 mg), mp 110−
112 °C. The ee was determined by chiral HPLC (Daicel
CHIRALPACK IC-H, hexane/iPrOH, 98:2, 0.6 mL/min, 214 nm).
Notes
The authors declare no competing financial interest.
Main product: tmajor = 66.7 min, tminor = 73.9 min. [α]20 = −20.6 (c
D
ACKNOWLEDGMENTS
1.30, CH2Cl2). 1H NMR (CDCl3, 400 MHz, TMS): δ 1.32 (t, J = 7.2
Hz, 3H, CH3), 2.39 (dd, J = 9.6 Hz, 14.0 Hz, 1H, CH2), 2.93 (dd, J =
7.6 Hz, 14.0 Hz, 1H, CH2), 3.69−3.79 (m, 1H, CH), 4.16 (d, J = 11.2
Hz, 1H, CH), 4.28 (q, J = 7.2 Hz, 2H, CH2), 4.69 (dd, J = 11.2 Hz,
11.2 Hz, 1H, CH), 5.17 (dd, J = 0.8 Hz, 9.6 Hz, 1H, CH2), 5.23 (d,
J = 16.8 Hz, 1H, CH2), 5.48−5.58 (m, 1H, CH), 7.39−7.48 (m,
5H, ArH). 13C NMR (CDCl3, 100 MHz, TMS): δ 13.8, 41.5, 43.2,
43.8, 51.7, 54.9, 63.0, 113.9, 114.4, 120.3, 128.0, 129.2, 129.5, 132.4,
134.1, 159.9, 191.1. IR (CH2Cl2): ν 2965, 2923, 1726, 1443, 1370,
1296, 1260, 1210, 1094, 1063, 1043, 933, 856, 740, 700 cm−1. MS
(ESI) m/z (%): 323.0 (100) [M+ + H]. HRMS (ESI): calcd for
C19H18N2O3Na+ (M+ + Na) requires 345.1210, found 345.1225.
General Procedure for the Synthesis of 9. To a solution of
(2S,3S,4R)- dimethyl 3-(2-tert-butoxy-2-oxoacetyl)-2-phenyl-4-vinyl-
cyclopentane-1,1-dicarboxylate (6q; 1.0 equiv) in DCM (0.1 M) was
added CF3COOH (10 equiv) slowly at room temperature, and the
reaction was stirred at room temperature for 24 h. The mixture was
concentrated in vacuo to yield the crude product, which was purified
by flash chromatography on silica gel (eluent: PE/EtOAc, 2:1) to
furnish the desired acid as a colorless oil.
■
We thank the Shanghai Municipal Committee of Science and
Technology (11JC1402600), National Basic Research Program
of China (973-2010CB833302), the Fundamental Research
Funds for the Central Universities, and the National Natural
Science Foundation of China for financial support (20902019,
20872162, 20672127, 21121062, 20732008, 20772030, and
20702059).
REFERENCES
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(2S,3S,4R)-Dimethyl 3-(2-(4-bromobenzylamino)-2-oxoace-
tyl)-2-phenyl-4-vinylcyclopentane-1,1-dicarboxylate, 9: white
solid, 51% yield (24 mg), mp 102−105 °C. The ee was determined by
chiral HPLC (Daicel CHIRALPACK OJ-H, hexane/iPrOH, 70:30, 0.5
mL/min, 230 nm). Main product: tmajor = 23.8 min, tminor = 32.9 min.
[α]20D = −8.5 (c 0.8, CH2Cl2). 1H NMR (CDCl3, 400 MHz, TMS): δ
2.09 (dd, J = 4.4 Hz, 14.0 Hz, 1H, CH2), 3.13 (dd, J = 7.6 Hz, 14.0 Hz,
1H, CH2), 3.18 (s, 3H, CH3), 3.69−3.735 (m, 1H, CH), 3.74 (s, 3H,
CH3), 4.29 (dd, J = 6.4 Hz, 14.8 Hz, 1H, CH2), 4.42 (dd, J = 6.4 Hz,
14.8 Hz, 1H, CH2), 4.62 (d, J = 11.6 Hz, 1H, CH), 4.70 (dd, J = 8.4
Hz, 11.6 Hz, 1H, CH), 4.94 (d, J = 10.0 Hz, 1H, CH2), 5.01 (d, J =
16.8 Hz, 1H, CH2), 5.54−5.63 (m, 1H, CH), 7.07 (d, J = 8.4 Hz,
2H, ArH), 7.18−7.30 (m, 5H, ArH), 7.42 (d, J = 8.4 Hz, 2H, ArH).
13C NMR (CDCl3, 100 MHz, TMS): δ 40.9, 42.6, 45.2, 49.9, 52.2,
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52.8, 54.0, 64.4, 117.1, 121.7, 127.3, 128.1, 128.5, 129.4, 131.8, 135.9,
137.3, 137.8, 159.7, 170.8, 172.3, 197.1. IR (CH2Cl2): ν 3349, 2952,
2925, 2853, 1726, 1678, 1522, 1488, 1456, 1434, 1254, 1209, 1175,
1103, 1071, 1011, 923, 795, 736, 700 cm−1. MS (ESI) m/z (%): 528.1
(7) Goldberg, A. F. G.; Stoltz, B. M. Org. Lett. 2011, 13, 4474−4476.
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Hayashi, T. Tetrahedron: Asymmetry 1998, 9, 1779−1787. (b) Deng,
H.-P.; Wei, Y.; Shi, M. Adv. Synth. Catal. 2009, 351, 2897−2902.
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+
(100) [M+ + 1]. HRMS (ESI): calcd for C26H27BrNO6 (M+ + H)
requires 527.0944, found 527.0932.
ASSOCIATED CONTENT
■
S
* Supporting Information
Spectroscopic data and chiral HPLC traces of the compounds
shown in Tables 1−3 and Schemes 2 and 3, detailed
descriptions of experimental procedures, and the crystal
structure of 8a (CCDC 872181), 8b (CCDC 883008), and 9
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