Asymmetric Allylation of 2-Oxocycloalkanecarboxylates

Article abstract of DOI:10.1055/s-0036-1588095

In this study, the highly enantioselective α-allylation of α-substituted β-ketoesters, particularly 2-oxocycloalkanecarboxylates, is achieved by synergistic catalysis with an achiral palladium complex and a chiral primary amino acid. Various α-allylated β-ketoesters containing a quaternary carbon stereogenic center are synthesized in high yields (up to 97%) with excellent enantioselectivity (up to 99% ee).

Full text of DOI:10.1055/s-0036-1588095

SYNTHESIS
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©
Georg Thieme Verlag Stuttgart · New York
2016, 48, A–F
A
paper
Synthesis
M. Yoshida et al.
Paper
Asymmetric Allylation of 2-Oxocycloalkanecarboxylates
Masanori Yoshida*a
Shohei Yanob
Shoji Harab
HO2C
NH2
O
(
CO2R1
O
OAc
OTBDPS
1
2
CO R
+
)n
Pd(OAc)2
P(4-FC6H4)3
(
)n
R2
a
Faculty of Mathematics and Science, National Institute of Technology,
R2
Asahikawa College, 2-1-6, Shunko-dai 2-jo, Asahikawa, Hokkaido
0
71-8142, Japan
yield up to 97%
ee up to 99%
b
Molecular Chemistry and Engineering Course, Graduate School of Chemical
Sciences and Engineering, Hokkaido University, Kita 13-jo Nishi 8, Kita-ku,
Sapporo, Hokkaido 060-8628, Japan
9
examples
yoshida@edu.asahikawa-nct.ac.jp
Received: 24.09.2016
Accepted: 21.10.2016
Published online: 24.11.2016
ciphylline B type alkaloid, isodaphlongamine H, using 1-
prop-2-enyl)-2-oxocyclopentanecarboxylate.7 Thus, α-al-
(
DOI: 10.1055/s-0036-1588095; Art ID: ss-2016-f0664-op
lylated β-ketoesters, particularly 1-(prop-2-enyl)-2-oxocy-
cloalkanecarboxylates, are potentially attractive as synthet-
ic intermediates. Although the asymmetric α-allylation of
Abstract In this study, the highly enantioselective α-allylation of α-
substituted β-ketoesters, particularly 2-oxocycloalkanecarboxylates, is
achieved by synergistic catalysis with an achiral palladium complex and
a chiral primary amino acid. Various α-allylated β-ketoesters containing
a quaternary carbon stereogenic center are synthesized in high yields
2-oxocycloalkanecarboxylates is straightforward for obtain-
ing 1-(prop-2-enyl)-2-oxocycloalkanecarboxylates in a ste-
reoselective manner, it is still challenging to achieve allyla-
(
up to 97%) with excellent enantioselectivity (up to 99% ee).
8
tion with high enantioselectivity by asymmetric catalysis.
Indeed, enantiopure 1-(prop-2-enyl)-2-oxocyclopentan-
ecarboxylate is generally prepared by kinetic reduction of
the racemate with baker’s yeast.6 Recently, we reported
that synergistic catalysis using an achiral palladium com-
plex and a chiral primary amino acid was effective for the
asymmetric α-allylation of α-branched aldehydes, and a
quaternary carbon stereogenic center possessing four sub-
Key words allylation, amino acids, asymmetric catalysis, ketones, pal-
ladium
,7,9
The stereoselective construction of quaternary carbon
stereogenic centers is frequently required in the total syn-
thesis of complex organic molecules, such as natural organ-
ic compounds; nevertheless, it remains one of the challeng-
stituents (allyl, alkyl, aryl, and formyl groups) was con-
1,2
10–12
ing topics in organic synthesis. Furthermore, for accurate-
ly synthesizing a target molecule, it is imperative to
introduce functional groups into synthetic intermediates,
as well as for additional carbon–carbon bond formation re-
actions. For furnishing synthetic intermediates with a qua-
ternary carbon stereogenic center and functional groups,
the α-allylation of α-substituted β-ketoesters is attractive
as both a quaternary carbon stereogenic center and multi-
ple functional groups, such as carbonyl, alkoxycarbonyl,
structed with high enantioselectivity.
In this study, the
α-allylation of α-substituted β-ketoesters, particularly 2-
oxocycloalkanecarboxylates, via synergistic catalysis using
an achiral palladium complex and a chiral primary amino
acid is described.
Pohmakotr et al.
F
OH
F
R2
3
O
and allyl, are simultaneously obtained. By employing 2-
CO2R1
CO2R1
oxocycloalkanecarboxylates as β-ketoester substrates for al-
lylation, synthetically useful 1-(prop-2-enyl)-2-oxocycloal-
kanecarboxylates, which can be converted into various
complex cyclic compounds, such as fused-ring and spiro
compounds, are obtained. For example, the groups of
Keay et al.
N3
O
Scheme 1 Transformation of 1-(prop-2-enyl)-2-oxocyclopentanecar-
boxylate into bicyclo[3,3,0]octane and spiro[4.4]nonane
4
5
Pohmakotr and Keay have successfully synthesized bicy-
clo[3,3,0]octane and spiro[4.4]nonane, respectively, from 1-
(
prop-2-enyl)-2-oxocyclopentanecarboxylate (Scheme 1).6
Hanessian et al. have reported the total synthesis of a caly-
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

B
Synthesis
M. Yoshida et al.
Paper
For optimizing the reaction conditions for the allylation,
ethyl 2-oxocyclopentanecarboxylate (2a) and allyl acetate
3a) were chosen as model substrates. The screening of cat-
alysts with amino acids 4 was performed in the presence of
reaction vessel at the end of each experiment. As expected,
lipophilic primary amino acids 4f–k, which contain a siloxy
group in the side chain, afforded allylated product 1a in
moderate-to-good enantioselectivity.13 Finally, the use of
O-tert-butyldiphenylsilyl L-threonine (4k) as the catalyst
afforded a better enantioselectivity compared with those
observed for the other amino acids.
Next, the reaction conditions were optimized with re-
spect to the amount of allyl acetate (3a), the reaction tem-
perature, and the concentration of 2a in toluene; Table 2
shows the results obtained. By decreasing the amount of 3a,
the enantioselectivity of the allylation was improved to 90%
ee, although the reaction was slow (Table 2, entries 1 and
2). The concentration of the substrates in the solvent also
affected the reaction rate, with the allylation proceeding at
a more rapid rate in a reduced amount of the solvent (Table
2, entries 3 and 4). When the allylation was conducted at
40 °C, the reaction rate was improved without significant
loss of the enantioselectivity, although the reaction termi-
nated in a short time at 60 °C (Table 2, entries 5–7). Hence,
further investigation of the allylation was conducted using
2a (0.5 mmol) in toluene (0.6 mL) at 40 °C (Table 2, entry 6).
(
tetrakis(triphenylphosphine)palladium(0) [Pd(PPh ) ] in
3
4
toluene at 25 °C, and Table 1 summarizes the results ob-
tained. The reaction time was maintained constant at 16
hours for evaluating the activity of the amino acid catalysts.
Allylation in the presence of a catalytic amount of naturally
occurring amino acids, such as proline (4a), alanine (4b),
valine (4c), leucine (4d), and phenylalanine (4e), afforded
ethyl 1-(prop-2-enyl)-2-oxocyclopentanecarboxylate (1a)
in 32–46% yields, albeit with very low enantioselectivity
(
0–5% ee). As allylation in the absence of an amino acid cat-
alyst gave a similar result (46%, 0% ee), amino acids 4a–e
were not found to be effective as catalysts for allylation. The
results with low enantioselectivity can be explained by the
low solubility of amino acids 4a–e in an organic solvent, as
white solids due to the amino acids were observed in the
Table 1 Screening of Amino Acid Catalysts 4 for the Allylation of Ethyl
2
-Oxocyclopentanecarboxylate (2a) with Allyl Acetate (3a) in the Pres-
a
ence of Pd(PPh3)
4
Table 2 Optimization of the Reaction Conditions Relative to the
Amount of Allyl Acetate (3a), Reaction Temperature, and Concentration
of Ketoester 2a in Toluenea
O
O
OAc
4
CO2Et
CO2Et
+
Pd(PPh3)4
toluene
Entry
Temp (°C)
Concn (M)
b
Yield (%)
c
ee (%)
d
2
a
3a
1a
1e
2
25
25
25
25
40
40
60
0.50
0.50
0.83
1.30
0.50
0.83
0.83
66
41
86
84
52
91
23f
64
90
78
76
85
87
31
Amino acid catalyst 4, yield of 1a,b eec
3
CO2H
NH2
CO2H
none
4
N
H
5
46%, 0% ee
4a, 32%, 2% ee
CO2H
4b, 44%, 2% ee
6
CO H
2
7
CO2H
NH2
a
NH2
NH2
Ph
Unless otherwise mentioned, the reaction was carried out with 2a (0.5
mmol), 3a (1.0 mmol), 4k (0.1 mmol), and Pd(PPh ) (0.025 mmol) in tolu-
3 4
ene for 16 h.
b
Concentration of 2a in toluene. The amount of toluene used was 1.0 mL
0.50 M), 0.60 mL (0.83 M), and 0.40 mL (1.30 M).
Yield of isolated product 1a.
4
c, 44%, 2% ee
4d, 46%, 0% ee
4e, 46%, 5% ee
(
c
CO2H
CO2H
d
e
f
Determined by chiral HPLC analysis.
NH2
NH2
CO2H
An increased amount of 3a (1.25 mmol) was used.
A large amount of unreacted 2a remained.
NH2
OTBS
OTBS
OTBDPS
Next, the screening of ligands on the palladium catalysts
4
f, 76%, 48% ee
CO2H
4g, 72%, 60% ee
4h, 36%, 41% ee
was conducted using palladium(II) acetate [Pd(OAc) ] and
2
various organophosphines; Table 3 shows the results ob-
tained. The use of triphenylphosphine (PPh ) with Pd(OAc)
CO2H
CO2H
3
2
NH2
NH2
NH2
furnished results similar to those obtained with Pd(PPh ) ,
3
4
OTBDPS
OTBS
OTBDPS
and the use of two equivalents of PPh relative to Pd(OAc)
was found to be optimum (Table 3, entries 1–6). Although
3
2
4
i, 54%, 52% ee
4j, 78%, 61% ee
4k, 66%, 64% ee
a
The reaction was carried out with 2a (0.5 mmol), 3a (1.25 mmol), 4 (0.1
(0.025 mmol) in toluene (1 mL) at 25 °C for 16 h.
tris(o-tolyl)phosphine [P(2-CH C H ) ] and tris(pentafluo-
3
6
4 3
3 4
mmol), and Pd(PPh )
b
Yield of isolated product 1a.
rophenyl)phosphine [P(C F ) ] were not effective for allyla-
6 5 3
c
Determined by chiral HPLC analysis.
tion, tris(4-fluorophenyl)phosphine [P(4-FC H ) ] afforded
6
4 3
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

C
Synthesis
M. Yoshida et al.
Paper
1
a in 90% yield and 95% ee (Table 3, entries 7–9). Bidentate
ligands such as 1,2-bis(diphenylphosphino)ethane (dppe),
,3-bis(diphenylphosphino)propane (dppp), 1,4-bis(di-
entries 1 and 2). The effect of the alkoxycarbonyl group of
2-oxocyclopentanecarboxylates 2a–c on the allylation was
investigated, and the results indicated that the bulkiness of
the alkoxycarbonyl group did not significantly affect the
yields and enantiomeric excesses of the allylated products
1a–c (Table 4, entries 2–4). On the other hand, the struc-
tures of the β-ketoesters 2 significantly affected their reac-
tivity. For example, cyclohexanonecarboxylate 2d, which
has a ring size greater than that of cyclopentanone, re-
quired a reaction time longer than that required by 2a (Ta-
ble 4, entry 5). By increasing the catalyst loading of the Pd
complex, the reaction time was considerably reduced (Table
4, entry 6),14 and cycloheptanonecarboxylate 2e also afford-
ed allylated product 1e in high yield and with excellent en-
antioselectivity (Table 4, entry 7). The allylation of an acy-
clic β-ketoester, ethyl 2-methyl-3-oxobutanoate (2f), was
very sluggish, affording allylated product 1f in 42% yield,
with a significant amount of unreacted substrates even
when the reaction was conducted for 120 hours with an in-
creased catalyst loading of the Pd complex (Table 4, entry
8). Next, the effect of the α-substituents of β-ketoesters 2f–
h on the allylation was investigated, and the results indicat-
ed that the allylation was sensitive to steric hindrance at
the α-carbon atom (Table 4, entries 8–10). Although the al-
lylation of 2-ethoxycarbonyl-1-indanone (2i) using 3a af-
forded allylated product 1i in 87% yield, no enantioselectivi-
ty was observed (Table 4, entry 11). The reaction between
aromatic ketones and the amino acid catalyst probably af-
forded insufficient enamine, which is a possible intermedi-
ate in the allylation.15 The current allylation of 2a can be ap-
plied to the reaction with trans-cinnamyl acetate (3b), af-
fording the corresponding allylated product 1j in high yield
and with excellent enantioselectivity (Table 4, entry 12).
By comparing the spectroscopic data with those report-
ed previously, both cyclic product 1a and acyclic product 1f
were found to be R-enantiomers.16 With these results, a
plausible mechanism was proposed for the stereocontrol of
the allylation (Scheme 2). By the formation of an intramo-
lecular hydrogen bond between NH and CO, enamine Im-1,
generated from β-ketoester 2 and amino acid 4k, possibly
adopts Z-geometry. Next, the acetate ion of a π-allylpalladi-
um complex, generated from Pd(OAc) , P(4-FC H ) , and al-
1
phenylphosphino)butane (dppb), 1,1′-bis(diphenylphosphi-
no)ferrocene (dppf), and 2,2′-bis(diphenylphosphino)-1,1′-
binaphthyl (BINAP) furnished results that were worse than
those obtained with the use of PPh and P(4-FC H ) (Table
3
6
4 3
3, entries 10–14). As both racemic and chiral forms of
BINAP furnished the same enantiomer with similar enan-
tiomeric excess, the stereocontrol for the current allylation
significantly depends on the chirality of the amino acid cat-
alyst used (Table 3, entries 14–16). Thus, P(4-FC H ) was
chosen as the ligand on the palladium catalyst for the allyla-
tion reactions.
6
4 3
Table 3 Screening of Ligands on the Palladium Catalyst for the Allyla-
tion of Ketoester 2a with Allyl Acetate (3a) in the Presence of Amino
Acid Catalyst 4k
a
Entry
Ligand (mol%)
Yield (%)b
ee (%)c
1d
none
none
91
nr
87
nd
nd
86
87
88
nd
nd
95
nd
nd
84
84
57
66
60
2
3
4
5
6
7
8
9
PPh
PPh
PPh
PPh
3
3
3
3
(5)
trace
94
92
81
nr
(10)
(15)
(20)
P(2-MeC
6 4 3
H ) (10)
P(C (10)
6
F
5
)
3
nr
P(4-FC
6
H
4
)
3
(10)
90
nr
e
1
1
1
1
1
1
0
1
2
3
4
5
6
dppe (5)
f
dppp (5)
trace
8
dppbg (5)
dppfh (5)
72
44
60
44
i
(±)-BINAP (5)
(R)-BINAP (5)
(S)-BINAP (5)
1
a
Unless otherwise mentioned, the reaction was carried out with 2a (0.5
2
mmol), 3a (1.0 mmol), 4k (0.1 mmol), and Pd(OAc) (0.025 mmol) in tolu-
ene (0.6 mL) at 40 °C for 16 h.
b
Yield of isolated product 1a. nr = no reaction.
Determined by chiral HPLC analysis. nd = not determined.
2
6
4 3
c
lyl acetate 3a, is exchanged with the carboxyl group of Im-
d
e
f
Pd(PPh
,2-Bis(diphenylphosphino)ethane.
,3-Bis(diphenylphosphino)propane.
3 4 2
) was used instead of Pd(OAc) .
1, affording Im-2.1
0,17
As the Re-face of the α-carbon atom of
1
1
the enamine comes closer to the π-allylpalladium moiety as
compared to the Si-face, allylation predominantly occurs at
the Re-face, furnishing an R-enantiomer.
g
h
i
1
,4-Bis(diphenylphosphino)butane.
,1′-Bis(diphenylphosphino)ferrocene.
,2′-Bis(diphenylphosphino)-1,1'-binaphthyl.
1
2
In conclusion, a primary amino acid, O-TBDPS L-thre-
onine (4k), is an effective asymmetric catalyst for the α-al-
lylation of α-substituted β-ketoesters, particularly 2-oxocy-
cloalkanecarboxylates. Allylation proceeds under mild reac-
tion conditions, furnishing various α-allylated β-ketoesters
possessing a quaternary carbon stereogenic center in high
yields and with excellent enantioselectivities.
Finally, the substrate scope of the present allylation was
investigated; Table 4 shows the results obtained. By de-
creasing the reaction temperature from 40 °C to 25 °C,
higher enantioselectivity was observed, albeit the reaction
took a longer time for completion, and the allylation of 2a
with 3a afforded 1a in 92% yield and with 98% ee (Table 4,
©
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D
Synthesis
M. Yoshida et al.
Paper
Table 4 Substrate Scopea
O
O
CO2R3
CO2R3
R4
4k
R1
R1
+
AcO
Pd(OAc)2, P(4-FC6H4)3
toluene, 25 °C
R2
R2
R4
2
3
1
Entry
Ketoester
Allyl acetate
Time (h)
Product
Yield (%)b
ee (%)c
1d
2
2a [R –R = (CH
1
2
)
)
, R3 = Et]
, R3 = Et]
3a (R4 = H)
3a (R4 = H)
3a (R4 = H)
3a (R4 = H)
3a (R4 = H)
3a (R4 = H)
3a (R4 = H)
3a (R4 = H)
3a (R4 = H)
3a (R4 = H)
3a (R4 = H)
16
24
1a
1a
1b
1c
1d
1d
1e
1f
90
92
96
97
87
91
86
42
nr
95
98
98
98
96
96
99
94
nd
nd
0
2
2
3
1
2
2a [R –R = (CH
3
1
2
, R3 = Me]
, R3 = Bn]
3
2b [R –R = (CH
2
)
3
24
1
2
4
2c [R –R = (CH
2
)
3
24
1
2
, R3 = Et]
, R3 = Et]
4
5
2d [R –R = (CH
2
2
)
)
4
120
72
6e
7e
8e
9
2d [R –R = (CH
1
2
1
2
, R3 = Et]
2e [R –R = (CH
2
)
5
120
120
72
2f (R1 = R2 = Me, R3 = Et)
2g (R1 = Me, R2 = Ph, R3 = Et)
2h (R1 = Me, R2 = H, R3 = Et)
1g
1h
1i
10
72
73
87
84
1
1e
2e
2i (2-CO
2
Et-1-indanone)
240
144
1
2
, R3 = Et]
3b (R4 = Ph)
1
2a [R –R = (CH
2
)
3
1j
98
a
2 6 4 3
Unless otherwise mentioned, the reaction was carried out with 2 (0.5 mmol), 3 (1.0 mmol), 4k (0.1 mmol), Pd(OAc) (0.025 mmol), and P(4-FC H ) (0.05
mmol) in toluene (0.6 mL) at 25 °C.
b
Yield of isolated product 1. nr = no reaction.
Determined by chiral HPLC analysis. nd = not determined.
The reaction was carried out at 40 °C.
2 6 4 3
Increased amounts of Pd(OAc) (0.05 mmol) and P(4-FC H ) (0.10 mmol) were used.
c
d
e
Ketoesters 2a,b,d,f,h were purchased and used after distillation; ke-
18a
18b
18c
18d
toesters 2c, 2e, 2g, and 2i were synthesized according to lit-
erature procedures. Allyl acetates 3a,b were purchased and used after
distillation. Amino acids 4a–e were purchased and used without puri-
fication. O-Silylated L-tyrosines 4f,g, L-serines 4h,i, and L-threonines
Y
CO2H
H
H
O
N
R1
AcOPd(Ln)Allyl
AcOH
EtO
13
4j,k were synthesized according to the literature. Palladium cata-
R2
lysts and phosphine ligands were purchased and used without purifi-
cation. Purification of the products was accomplished by column
chromatography on Kanto Chemical Co., Inc. Silicagel 60N (spherical,
neutral; 63–210 μm). Specific rotations were measured using a HORI-
Im-1
Y
CO2Pd(Ln)Allyl
H
H
O
N
1
13
BA SEPA-500 polarimeter. H NMR and C NMR spectra were record-
ed on a JNM-ECS400 FT NMR spectrometer. Chemical shifts (δ) are
referenced with respect to TMS as an internal standard. HPLC was car-
ried out using a JASCO PU-2089 Plus intelligent pump and a UV-2075
Plus UV detector.
EtO
R1
Y = TBDPSO
R2
Im-2
Y
Y
H
H
H
Allyl(Ln)Pd
Allyl(Ln)Pd
O2C
Ethyl (R)-1-(Prop-2-enyl)-2-oxocyclopentanecarboxylate (1a);
Typical Procedure
O2C
EtO2C
H
CO2Et
R1
R1
To a 7 mL vial were added Pd(OAc)2 (5.6 mg, 0.025 mmol), P(4-F-
R2
R2
C H ) (15.6 mg, 0.05 mmol), O-TBDPS L-threonine (4k) (35.7 mg, 0.1
6
4 3
Re-face
Si-face
mmol) and toluene (0.6 mL). After the mixture became homogeneous,
allyl acetate (3a) (100 mg, 1 mmol) and ethyl 2-oxocyclopentanecar-
boxylate (2a) (78 mg, 0.5 mmol) were added and the mixture was
stirred for 24 h at 25 °C. The resulting mixture was filtered through a
O
CO2Et
R2
R1
small plug of silica gel, eluted with Et O (4 × 1 mL) and concentrated
2
under reduced pressure. Ethyl (R)-1-(prop-2-enyl)-2-oxocyclopen-
tanecarboxylate (1a) was isolated by column chromatography (silica
Scheme 2 A plausible mechanism for the stereocontrol
gel, hexane–Et O, 9:1). The enantioselectivity was determined by chi-
2
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

E
Synthesis
M. Yoshida et al.
Paper
ral HPLC analysis. The absolute configuration was determined by
comparison of the specific rotation with that reported in the litera-
ture. Spectroscopic data are in agreement with the published data.
Yield: 38.6 mg (42%); colorless oil; [α]58924 +23.7 (c 1.0, CHCl );
3
ee = 94%; R = 0.37 (n-hexane–EtOAc, 9:1).
f
6a
4
1
H NMR (400 MHz, CDCl ): δ = 1.24 (t, J = 7.2 Hz, 3 H), 1.30 (s, 3 H),
3
Yield: 90.2 mg (92%); colorless oil; [α]58924 –38.4 (c 1.0, CHCl );
2.13 (s, 3 H), 2.45–2.64 (m, 2 H), 4.17 (q, J = 7.2 Hz, 2 H), 5.05–5.10 (m,
3
ee = 98%; R = 0.43 (n-hexane–EtOAc, 4:1).
2 H), 5.57–5.68 (m, 1 H).
f
1
13
H NMR (400 MHz, CDCl ): δ = 1.22 (t, J = 7.2 Hz, 3 H), 1.83–2.06 (m, 3
C NMR (100 MHz, CDCl ): δ = 14.2, 19.0, 26.3, 39.4, 59.5, 61.5, 119.1,
3
3
H), 2.17–2.26 (m, 1 H), 2.31–2.47 (m, 3 H), 2.62–2.67 (m, 1 H), 4.11–
132.7, 172.6, 205.2.
4.17 (m, 2 H), 5.06–5.10 (m, 2 H), 5.61–5.72 (m, 1 H).
13
C NMR (100 MHz, CDCl ): δ = 14.2, 29.6, 32.2, 37.9, 38.2, 60.0, 61.5,
3-Ethoxycarbonylhex-5-en-2-one (1h)
3
Spectroscopic data are in agreement with the published data.19d
119.2, 133.1, 171.0, 214.8.
Yield: 62.1 mg (73%); colorless oil; R = 0.23 (n-hexane–EtOAc, 9:1).
f
Methyl (R)-1-(Prop-2-enyl)-2-oxocyclopentanecarboxylate (1b)
Spectroscopic data are in agreement with the published data.19a
Yield: 87.4 mg (96%); colorless oil; [α]58924 –51.7 (c 1.0, CHCl );
1
H NMR (400 MHz, CDCl ): δ = 1.28 (t, J = 7.0 Hz, 3 H), 2.24 (3H s),
3
2.58–2.62 (m, 2 H), 3.53 (t, J = 7.6 Hz, 1 H), 4.17 (m, 2 H), 5.03–5.13
(m, 2 H), 5.70–5.80 (m, 1 H).
3
ee = 98%; R = 0.46 (n-hexane–EtOAc, 4:1).
13
f
C NMR (100 MHz, CDCl ): δ = 14.2, 29.2, 32.3, 59.3, 61.5, 117.6,
3
1
H NMR (400 MHz, CDCl ): δ = 1.85–2.04 (m, 3 H), 2.18–2.27 (m, 1 H),
134.3, 169.3, 202.7.
3
2.32–2.49 (m, 3 H), 2.62–2.68 (m, 1 H), 3.69 (s, 3 H), 5.06–5.11 (m, 2
H), 5.61–5.71 (m, 1 H).
2
-Ethoxycarbonyl-2-(prop-2-enyl)-1-indanone (1i)
13
Spectroscopic data are in agreement with the published data.8e
C NMR (100 MHz, CDCl ): δ = 19.6, 32.2, 38.0, 38.2, 52.7, 60.1, 119.3,
3
133.0, 171.4, 214.7.
Yield: 106.1 mg (87%); colorless oil; R = 0.51 (n-hexane–EtOAc, 4:1).
f
1
H NMR (400 MHz, CDCl ): δ = 1.21 (t, J = 7.0 Hz, 3 H), 2.58–2.92 (m, 2
3
Benzyl 1-(Prop-2-enyl)-2-oxocyclopentanecarboxylate (1c)
Spectroscopic data are in agreement with the published data.19b
Yield: 125.1 mg (97%); colorless oil; [α]58924 –27.0 (c 1.0, CHCl );
H), 3.12–3.67 (m, 2 H), 4.14–4.20 (m, 2 H), 5.03–5.16 (m, 2 H), 5.59–
5.70 (m, 1 H), 7.38–7.78 (m, 4 H).
3
13
C NMR (100 MHz, CDCl ): δ = 14.2, 36.1, 39.2, 60.1, 61.8, 119.4,
3
ee = 98%; R = 0.51 (n-hexane–EtOAc, 4:1).
f
124.8, 126.5, 127.8, 132.9, 135.3, 135.5, 153.2, 170.8, 202.3.
1
H NMR (400 MHz, CDCl ): δ = 1.84–2.03 (m, 3 H), 2.18–2.27 (m, 1 H),
3
2
.32–2.49 (m, 3 H), 2.65–2.70 (m, 1 H), 5.04–5.09 (m, 2 H), 5.13 (s, 2
Ethyl 1-(3-Phenylprop-2-enyl)-2-oxocyclopentanecarboxylate (1j)
Spectroscopic data are in agreement with the published data.4
H), 5.60–5.71 (m, 1 H), 7.28–7.37 (m, 5 H).
13
C NMR (100 MHz, CDCl ): δ = 19.6, 32.2, 37.9, 38.2, 60.0, 67.2, 119.3,
Yield: 114.2 mg (84%); colorless oil; [α]58924 –60.6 (c 1.0, CHCl );
3
3
128.0, 128.4, 128.7, 133.0, 135.7, 170.9, 214.5.
ee = 98%; R = 0.54 (n-hexane–EtOAc, 4:1).
f
1
H NMR (400 MHz, CDCl ): δ = 1.25 (t, J = 7.2 Hz, 3 H), 1.86–2.08 (m, 3
3
Ethyl (R)-1-(Prop-2-enyl)-2-oxocyclohexanecarboxylate (1d)
Spectroscopic data are in agreement with the published data.8g
Yield: 95.6 mg (91%); colorless oil; [α]58924 +130.3 (c 1.0, CHCl );
H), 2.19–2.29 (m, 1 H), 2.39–2.55 (m, 3 H), 2.78–2.83 (m, 1 H), 4.14–
4.20 (m, 2 H), 6.08 (dt, J = 7.2, 16.0 Hz, 1 H), 6.44 (d, J = 16.0 Hz, 1 H),
7.18–7.33 (m, 5 H).
3
ee = 96%; R = 0.31 (n-hexane–EtOAc, 9:1).
13
f
C NMR (100 MHz, CDCl ): δ = 14.2, 19.7, 32.3, 37.1, 38.2, 60.4, 61.6,
3
1
H NMR (400 MHz, CDCl ): δ = 1.23 (t, J = 7.2 Hz, 3 H), 1.40–1.48 (m, 1
124.6, 126.3, 127.5, 128.6, 134.2, 137.1, 171.1, 214.9.
3
H), 1.55–1.78 (m, 3 H), 1.96–2.03 (m, 1 H), 2.28–2.34 (m, 1 H), 2.42–
2.49 (m, 3 H), 2.57–2.62 (m, 1 H), 4.17 (q, J = 7.2 Hz, 2 H), 5.00–5.04
(
1
m, 2 H), 5.67–5.78 (m, 1 H).
Acknowledgment
3
C NMR (100 MHz, CDCl ): δ = 14.3, 22.6, 27.6, 35.9, 39.4, 41.2, 60.9,
3
This work was supported in part by a Grant-in-Aid for Scientific Re-
search on Innovative Areas ‘Advanced Molecular Transformations by
Organocatalysts’ from MEXT, Japan (KAKENHI No. 24105501).
6
1.3, 118.4, 133.4, 171.6, 207.7.
Ethyl 1-(Prop-2-enyl)-2-oxocycloheptanecarboxylate (1e)
Spectroscopic data are in agreement with the published data.19c
Yield: 96.3 mg (86%); colorless oil; [α]58924 +85.1 (c 1.0, CHCl );
Supporting Information
3
ee = 99%; R = 0.69 (n-hexane–EtOAc, 4:1).
f
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588095.
1
H NMR (400 MHz, CDCl ): δ = 1.23 (t, J = 7.2 Hz, 3 H), 1.34–1.43 (m, 1
3
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p
p
o
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i
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f
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ortioIgnfmr oaitn
H), 1.58–1.81 (m, 6 H), 2.04–2.12 (m, 1 H), 2.29–2.47 (m, 2 H), 2.61–
2.75 (m, 2 H), 4.15 (q, J = 7.2 Hz, 2 H), 5.02–5.06 (m, 2 H), 5.65–5.76
(
1
m, 1 H).
References
3
C NMR (100 MHz, CDCl ): δ = 14.2, 24.6, 25.6, 30.0, 32.1, 39.7, 42.2,
3
61.3, 62.9, 118.7, 133.7, 172.1, 209.3.
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