Cobalt-catalyzed reductive carboxylation of α,β-unsaturated compounds with carbon dioxide

Article abstract of DOI:10.1246/bcsj.20150043

The gaseous carbon dioxide incorporation reaction with α,β-unsaturated compounds was examined in the presence of a catalytic amount of bis(acetylacetonato)cobalt(II) and using diethylzinc as a reductant. After screening with various electron-withdrawing g

Full text of DOI:10.1246/bcsj.20150043

Cobalt-Catalyzed Reductive Carboxylation of
α,β-Unsaturated Compounds with Carbon Dioxide
Chika Hayashi, Takuo Hayashi, and Tohru Yamada*
Department of Chemistry, Keio University, Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522
E-mail: yamada@chem.keio.ac.jp
Received: February 2, 2015; Accepted: March 4, 2015; Web Released: June 15, 2015
The gaseous carbon dioxide incorporation reaction with α,β-unsaturated compounds was examined in the presence
of a catalytic amount of bis(acetylacetonato)cobalt(II) and using diethylzinc as a reductant. After screening with various
electron-withdrawing groups, both α,β-unsaturated nitriles and carboxamides were found to efficiently capture carbon
dioxide to provide the corresponding carboxylates or malonates in good to excellent yields under mild conditions.
Carbon-carbon bond formation is one of the most important
subjects in organic synthetic chemistry. In 1973, Mukaiyama
reported the Lewis acid catalyzed crossed aldol reaction1 using
silyl enol ether as a metal enolate analogue, which has been
employed as a standard method in organic synthesis as it
does not require the use of strong bases. Much effort has been
exploited for the reaction to improve the catalytic efficiency
and stereoselectivity by screening metal elements.2 Also,
improvement of the enantioselectivity has been achieved by
optimizing the ligand design.3
Employing conjugate addition to provide the metal enolate
equivalent makes it possible to exclude base species from the
reaction by using a catalytic amount of metal catalysts and a
stoichiometric amount of reducing agent for α,β-unsaturated
carbonyl compounds. Isayama and Mukaiyama reported the
reductive aldol reaction for α,β-unsaturated nitriles catalyzed
by bis(acetylacetonato)cobalt(II) with phenylsilane in 1989.4
They proposed the reaction mechanism as follows (Scheme 1):
the phenylsilane reducing agent would promote the cobalt
catalyst to a cobalt-hydride equivalent, which would add α,β-
unsaturated compounds by 1,4-addition to form the cobalt
enolate equivalent. It would capture electrophiles to afford the
corresponding aldol adducts with exclusive regioselectivity at
the α-position of the electron-withdrawing group.
2-propanol with molecular oxygen, the oxidation-reduction-
hydration of alkenes was proposed.5 With use of sodium
borohydride,6 the catalytic enantioselective reduction of vari-
ous carbonyl compounds into optically active secondary
alcohols7 or amines8 was proposed. Under similar conditions,
the enantioselective 1,4-reduction of α,β-unsaturated carbox-
amides was reported.9
In order to construct frameworks for various complicated
organic compounds, small molecules with effective functional
groups, which are commonly obtained from the petrochemical
industry have usually been employed. On the other hand,
currently, renewable carbon resources, such as bio-ethanol or
carbon dioxide, have attracted much attention for organic
syntheses,10 from the viewpoint of sustainability with respect to
the limitations of petroleum resources. Also, from our research
group, the reaction of carbon dioxide with epoxides catalyzed
by cobalt(II) complexes11a and the reactions propargyl alcohols
and amines catalyzed by silver(I) salts11b,11c,11f-11j have been
reported. In these reactions, an oxygen or nitrogen nucleo-
phile attacked carbon dioxide to afford cyclic carbonates or
oxazolidinones as products. Whereas these products tend to
release carbon dioxide by hydrolysis, the corresponding
carboxylates produced by the carbon-carbon bond-forming
reaction with carbon dioxide should be stable enough to be
employed as further synthetic intermediates for carbon-carbon
frameworks. Among an array of methods for the carbon-carbon
bond-forming reaction with carbon dioxide,10,12 our group has
During the course of our continuing studies on cobalt(II)
complex catalysts with the combined use of reducing agents, a
number of synthetic reactions were reported; in the presence of
Ph
OH
E+ : PhCHO
cat. Co(II) complex
R
R
EWG
R
Hydride equivalent
EWG
Reductive aldol reaction
Co(II)
E+
E
O
OH
E+ : CO2
C
R
EWG
EWG
R
EWG
H
H
Reductive carboxylation
Scheme 1. Cobalt-catalyzed C-C bond formations via enolate equivalents.
862 | Bull. Chem. Soc. Jpn. 2015, 88, 862–870 | doi:10.1246/bcsj.20150043
© 2015 The Chemical Society of Japan

Table 1. Examination of Various Reductants for Reductive
Carboxylation
proposed the reactions of enolates with carbon dioxide. In the
presence of a silver(I) catalyst, various ketones containing an
alkyne group at the appropriate position afforded the corre-
sponding γ-lactone derivatives11d or dihydroisobenzofuran
derivatives11e in good to high yields under mild conditions.
As another way to form new carbon-carbon bonds with
carbon dioxide, carbon nucleophiles generated from various
olefins in the presence of transition metals with appropriate
reducing agents were reported. From styrene derivatives, the
combined use of a nickel catalyst and diethylzinc,13 or an iron
catalyst and Grignard reagent14 are examined to afford the
corresponding carboxylates effectively. The nickel catalyst
combined with diethylzinc also activated alkyne to trap carbon
dioxide regioselectively.15 Under the conditions using the palla-
dium pincer complex and triethylaluminum, allenes reacted
with carbon dioxide to give the carboxylate product regio-
selectively in high yield.16 In these studies on hydrocarbox-
ylation of olefins, metal-hydride species generated from the
catalyst and reducing agent, which is the common key inter-
mediate, produced the carbon nucleophiles from the substrates
to attack carbon dioxide. However, as for α,β-unsaturated com-
pounds of electron-deficient olefins, only a study on a photo-
reaction system using aluminum catalyst and diethylzinc was
reported12a to obtain the alkylcarboxylate products regioselec-
tively, but the substrate scope was not wide enough.
COOH
cat.Co(acac)2, CO2
Ph
Ph
CN
CN
Reductant (2.0 equiv)
1a
2a
Amount of Co(II) CO2 pressure Yield
Entrya) Reductant
complex/mol %
/MPa
/%
1b)
2b)
3
4
5
PhSiH3
PhSiH3
Et3B
Et2AlCl
Et2Zn
5
100
100
100
100
5
1.0
1.0
1.0
1.0
1.3
1.0
0.1
0
10
10
26
62
6
7
Et2Zn
Et2Zn
87c)
>99c)
5
a) Reactions were carried out on a 0.25 mmol scale with 1.5
mL of THF at 20 °C. b) Reaction was carried out in 1.5 mL of
1,2-dichloroethane at 70 °C. c) Yield after methylation with
TMS diazomethane.
the 5 mol % of cobalt(II) complex, the desired product 2a was
obtained in 87% with some dicarboxylate detected as a side
product. The side product seems to be generated by hydrolysis
of desired cyanocarboxylate in the reaction system. Eventually
the desired cyanocarboxylate was isolated in quantitative yield
under very mild conditions at ambient temperature under
atmospheric pressure of carbon dioxide probably because the
amount of water in the reaction solution decreased by heating
the reactor vessel before use (Entry 7).18
Based on these prior studies of the reductive aldol reaction
and carbon dioxide incorporative reaction, we examined the
reductive carboxylation reaction of α,β-unsaturated compounds
with carbon dioxide in the presence of cobalt(II) catalysts and
reducing agents.
The optimized conditions were successfully applied to vari-
ous α,β-unsaturated nitriles to afford the carboxylation products
(Table 2). New carbon-carbon bond formations with carbon
dioxide were exclusively observed at the α-position for all
the substrates in Table 2. 5-Phenylpent-2-enenitrile (1a) and its
derivatives with general substituents, such as alkyls, ethers,
esters, and halogens showed good reactivity to produce the
corresponding carboxylates 3a-3f after methyl esterification in
good-to-excellent yields (Entries 1-6). Carboxylic acids were
obtained as products of the reaction. Methyl esterification was
performed in order to make analysis easy as well as to confirm
if the product was correctly formed. The substrates with a
naphthyl group, benzyl group and shortened alkyl chain 1g-1i
also gave the products in high yields (Entries 7-9). From
cinnamonitrile, the corresponding product 3j was obtained in
81% yield (Entry 10). The β-methyl-substituted derivative was
found not to be a suitable substrate for this reaction (Entry 12),
in accordance with the 1,4-addition manner,17b,19 while the α-
methyl-substituted (Entry 11) and γ-methyl-substituted (Entry
13) α,β-unsaturated nitriles reacted with carbon dioxide to
afford the desired carboxylates in moderate-to-good yields. The
α-phenyl-substituted α,β-unsaturated nitrile could react with
carbon dioxide to give the carboxylated product in good yield
(Entry 14). The dihydronaphthalenes with a nitrile at the α-
position 1o and 1p reacted with carbon dioxide to afford the
products in good-to-high yield (Entries 15 and 16), while no
reaction proceeded for the corresponding β-methyl-substituted
nitrile 1q (Entry 17).
Results and Discussion
Cobalt-Catalyzed Reductive Carboxylation of α,β-Unsat-
urated Nitriles with Carbon Dioxide. According to an earlier
study of the reductive aldol reaction,4 5-phenylpent-2-enenitrile
(1a) was subjected to the reported conditions then reacted with
benzaldehyde to afford the corresponding aldol adduct in 88%
yield. Under the same reaction conditions with gaseous carbon
dioxide as an electrophile instead of aldehydes, the desired
product 2a was not obtained at all while the corresponding
saturated product was produced (Table 1, Entry 1). Since it
was assumed that the obtained saturated product was derived
from the 1,4-reduction of the starting α,β-unsaturated nitrile, we
presumed that the corresponding enolate equivalent should be
properly generated, but could not capture carbon dioxide. When
a stoichiometric amount of the cobalt complex was actually
employed to cover the low reactivity of the intermediate, the
desired product 2a was obtained in 10% yield (Entry 2). Thus
we confirmed that the desired reductive carboxylation actually
proceeds in the presence of the cobalt complex and a reducing
agent. Various reducing agents were then examined to improve
the product yield. Triethylborane, diethylaluminum chloride,
and diethylzinc were employed as reducing agents (Entries 3, 4,
and 5).17 Based on this examination, it was found that diethyl-
zinc is the most suitable reducing agent to capture carbon
dioxide in the reaction. Triethylborane showed a reactivity simi-
lar to that of phenylsilane. Diethylaluminum chloride showed
a better yield than those of the silane and borane, and above
all, diethylzinc gave the best yield. By using diethylzinc and
Based on the GC-MS analysis of the obtained products, a
small amount of the corresponding β-ethyl-substituted carbox-
Bull. Chem. Soc. Jpn. 2015, 88, 862–870 | doi:10.1246/bcsj.20150043
© 2015 The Chemical Society of Japan | 863

Table 2. Various α,β-Unsaturated Nitriles for Reductive Carboxylation
COOMe
cat.Co(acac)2
R
TMSCHN2
CN
R
CO2, Et2Zn
CN
1
3
Entrya)
Substrate
Product
Yield/%d)
1
2
Ar = Ph
3a
>99
COOMe
CN
= 4-Me-Ph
3b
3c
77
85e)
Ar
CN
Ar
3
= 4-CO2Et-Ph
4
5
6
7
8
= 4-Br-Ph
= 4-Cl-Ph
= 4-OMe-Ph
= OBn
3d
3e
3f
3g
3h
>99
>99
98
72
>99
= 1-Naph
CN
COOMe
9
3i
78
81
38
CN
Ph
Ph
Ph
Ph
COOMe
10b)
11b)
3j
3k
CN
Me
CN
COOMe
Me
CN
Ph
Ph
Ph
CN
COOMe
12b)
3l
9f)
HS
CN
CN
CN
Me
Me
Me
Me COOMe
13b)
14b)
3m
3n
67
66
Ph
Ph
CN
CN
COOMe
CN
Ph
Ph
CN
NC COOMe
15b)
16c)
R¤ = H
3o
3p
91
56
R¤ = OMe
R'
R'
CN
NC COOMe
Me
17b)
3q
0
Me
a) Reactions were carried out on a 0.25 mmol scale with 1.5 mL of THF at 20 °C under atmospheric
pressure of CO2 with 2 equiv of Et2Zn (ca. 1.0 M in n-hexane) in the presence of 5 mol % of
Co(acac)2. b) 10 mol % of Co(acac)2 and 4 equiv of Et2Zn were employed. c) 15 mol % of Co(acac)2
and 8 equiv of Et2Zn were employed. d) Isolated yield. e) 1.0 MPa of CO2. f) Diastereomer ratio =
60:40.
CN
NC COOMe
Et
1) CO2
Co(acac)2
Et2Zn
(1)
Et2Zn
2) TMSCHN2
R'
CN
R'
1
4
EtCo L
NC COOMe
Co
H
1) CO2
R'
R
(2)
HCo L
EWG
1o
1p
R' = H
2) TMSCHN2
R'
H
= OMe
3
Scheme 2. Cobalt-hydride 1,4-addition mechanism.
864 | Bull. Chem. Soc. Jpn. 2015, 88, 862–870 | doi:10.1246/bcsj.20150043
© 2015 The Chemical Society of Japan

Table 3. Scope of the Electron-Withdrawing Group
cat.Co(acac)2
CO2 (balloon)
COOMe
+
Et2Zna
TMSCHN2
Ph
Ph
EWG
EWG
THF, 20 °C
1
3
Entry
EWG
Conditions
Product
Yield/%
>99
20
1
2
3
A
A
B
3a
3r
CN
OEt
35
O
O
O
N(CH3)OCH3
N(CH3)Ph
4
B
3s
3t
complex
5
6
A
B
21
>99
7
8
9
R1 = Me, R2 = Bn
R1 = Et, R2 = Et
R1 = iPr, R2 = iPr
R1 = Ph, R2 = Ph
B
B
B
B
3u
3v
3w
3x
64
62
13
9
NR1R2
O
O
10
O
N
11
B
3y
82
a) Condition A involves 5 mol % of bis(acetylacetonato)cobalt(II) and 2 equiv of diethylzinc.
Condition B involves 10 mol % of bis(acetylacetonato)cobalt(II) and 4 equiv of diethylzinc.
ylate was detected under some conditions. From the α,β-
urated nitrile 1a, the corresponding carboxylated product 3a
was obtained in quantitative yield after methylation (Entry 1).
The ethyl α,β-unsaturated carboxylate 1r was subjected to these
conditions to afford the corresponding product 3r in only 20%
yield (Entry 2). When 10 mol % of the cobalt complex with 4
equivalents of zinc reagent (Conditions B) was reacted with
the carboxylate 1r, only 35% of the product was obtained
(Entry 3). At the end of the reaction, the substrate 1r was
almost consumed as determined by TLC analysis. The side
product was confirmed as the corresponding saturated ester.
To the Weinreb amide22 1s, the present carboxylation reac-
tion could not be applied (Entry 4). For N-methylanilide, the
corresponding carboxylated product 3t was obtained in only
21% yield under conditions A (Entry 5), while conditions B
afforded the carboxylated product in quantitative yield (Entry
6). Several carboxamides were examined under conditions B to
afford the products 3u-3x in moderate yields (Entries 7-10).
Conditions B were also effective for the morpholine amide 1y
to give the product 3y in 82% yield (Entry 11).
unsaturated nitrile 1p, the ethyl-substituted carboxylate 4p was
isolated in 12% yield. Then, we tried to perform the reaction
without the cobalt complex to find that the ethyl-substituted
carboxylate was detected in the GC-MS analysis whereas the
desired β-hydrogenated product was not detected (Scheme 2,
eq 1). This observation provided clear evidence that the
presence of the cobalt catalyst is crucial in order to generate
the desired metal enolate intermediate which is hydrated at the
β-position, via interposition of the generated cobalt-hydride
(eq 2). As one example, in regard to the bis(acetylacetonato)-
nickel(II) complex, the generation of nickel-hydride species
was reported as the result of the transmetalation between the
complex and alkylaluminum which would generate alkyl nickel
species followed by β-elimination.13-16,20 With respect to the
present reaction, the cobalt-hydride species generated by the
same process would add the α,β-unsaturated nitrile in the
1,4-addition manner to afford the resulting metal enolate
equivalent.
Cobalt-Catalyzed Reductive Carboxylation of α,β-Unsat-
urated Carboxamides with Carbon Dioxide. As long as
the cobalt-hydride equivalent could attack the substrates via
the 1,4-addition sequence, not only nitriles, but also other α,β-
unsaturated compounds with electron-withdrawing groups,
such as ketones, esters, and amides could be employed in
these carboxylation reactions. The derived malonate derivatives
from these substrates would be widely applied as useful build-
ing blocks in organic syntheses, especially for natural com-
pounds.21 For widening the application of the reaction, several
substrates with other electron-withdrawing groups were exam-
ined (Table 3). When the standard conditions involving 5
mol % of bis(acetylacetonato)cobalt(II) with 2 equivalents of
diethylzinc (Conditions A) was employed for the α,β-unsat-
After the electron-withdrawing group screening, we next
examined a variety of carboxylic substituents in the substrates.
As shown in Tables 4 and 5, substrates with both aliphatic and
aromatic carboxylic substituents could be used for the reac-
tion (Entries 1, 3, and 7). The methoxy, methyl, chloro, and
trifuluoromethyl group substituents well tolerated the reaction
conditions to give good-to-excellent product yields (Entries 2,
3, 5, and 6). Based on a comparison between Tables 4 and 5,
the yields of the anilides tended to be higher than those of
the corresponding morpholides overall, except for the sub-
strates with methyl and chloro substituents on the aromatic
ring (Entries 3 and 5) and the substrate with long alkyl chain
(Entry 8). As for the substrate with N-methyl anilide, a long
alkyl chain with the substrate tends to decrease the yield
Bull. Chem. Soc. Jpn. 2015, 88, 862–870 | doi:10.1246/bcsj.20150043
© 2015 The Chemical Society of Japan | 865

probably due to steric hindrance during the 1,4-addition step of
the cobalt-hydride (Table 4, Entry 8).
position would not disturb the reaction compared with the
substitution at the α-position (Entries 12 and 13).
The substrates with some substitutions close to the reactive
olefin site were screened to examine the limitation of the reac-
tion (Table 6). The substitution on both the α-position and β-
positions would almost entirely prevent the reaction to proceed
(Entries 2, 3, 6, and 7). The products were obtained in only
low-to-moderate yields from the phenyl substituted derivatives
at the α-position (Entries 4 and 5). In common with the conju-
gated addition reaction with nitriles, the methyl substitution at
the β-position prohibited the cobalt-hydride addition to itself
(Entries 10 and 11). The methyl substitution at the α-position
would reduce the accessibility from the metal enolate equiv-
alent to carbon dioxide, which eventually decreased the product
yields (Entries 8 and 9). The methyl substitution at the γ-
It is worth noting that geometric isomerization was observed
when we employed the substrate 1ba with a phenyl substituent
at the α-position of the carboxamide (Scheme 3). This result
may be explained as follows; during the reaction, the cobalt-
hydride intermediate could attack the substrate to form the
cobalt enolate equivalent but it could not trap carbon dioxide
due to its bulkiness around the reactive α-position. Also the
cobalt-hydride was kicked out via β-hydride elimination from
the enolate equivalent because of repulsion between the phenyl
group and amine group with isomerization of geometry.
We also tried to use the carboxamide conjugated with a triple
bond 1bb for the reaction. Actually, it was consumed in the
system like the α,β-unsaturated compound, but the product 5bb
was obtained in fully-saturated state (Scheme 4). Presumably,
once the product 2bb including the conjugated double bond
was generated by the first reaction, it could be attacked again
by another cobalt-hydride intermediate for it still contained a
reactive site to give the fully-saturated product.
Table 4. Scope of the N-Methylanilide Derivatives
O
OMe
N
cat.Co(acac)2
Et2Zna
Me
N
Me
Ph
TMSCHN2
R1
R1
Ph
balloon CO2
THF, 20 °C
1
3
O
O
Conclusion
Entry
R1
Product
Yield/%
We studied the reductive carboxylation of α,β-unsaturated
nitriles and carboxamides with gaseous carbon dioxide. A
1
2
3
4
5
6
7
8
PhCH2CH2
4-MeOPh
4-MePh
Ph
4-ClPh
4-CF3Ph
Me
3t
3z
>99
77
65
88
67
98
80
20
3aa
3ab
3ac
3ad
3ae
3af
Table 6. Limitation of Substrates
cat.Co(acac)2
Et2Zna
COOMe
TMSCHN2
R
CONR1R2
R
CONR1R2
balloon CO2
THF, 20 °C
1
3
C5H11
Entry
1
Substrate
R1
Me
Me
R2
Bn
Ph
Product Yield/%
a) 10 mol % of bis(acetylacetonato)cobalt(II) and 4 equiv of
diethylzinc were used (condition B).
O
3an
78
Ph
NR1R2
Table 5. Scope of the Morpholine Amide Derivatives
O
2
3
4
5
6
3ao
3ap
3aq
3ar
3as
trace
trace
37
O
OMe
N
cat.Co(acac)2
Et2Zna
Ph
NR1R2
O
O
morpholine
Me Ph
morpholine
Me Ph
morpholine
Me Ph
morpholine
Me Ph
morpholine
Me Ph
morpholine
Me
TMSCHN2
R1
N
R1
O
balloon CO2
THF, 20 °C
NR1R2
NR1R2
NR1R2
1
3
O
O
40
Ph
O
Entry
R1
Product
Yield/%
trace
1
2
3
4
5
6
7
8
PhCH2CH2
4-MeOPh
4-MePh
Ph
4-ClPh
4-CF3Ph
Me
3y
92
70
90
68
75
63
44
53
7
8
3at
trace
17
3ag
3ah
3ai
3aj
3ak
3al
3au
3av
3aw
3ax
3ay
3az
O
9
10
10
11
12
13
12
15
O
NR1R2
NR1R2
O
94
50
C5H11
3am
a) 10 mol % of bis(acetylacetonato)cobalt(II) and 4 equiv of
diethylzinc were used (condition B).
a) 10 mol % of bis(acetylacetonato)cobalt(II) and 4 equiv of
diethylzinc were used (condition B).
O
10 mol% Co(acac)2
O
Ph
O
4 eq. Et2Zn
(E)
(E)
+
Ph
N
Ph
N
N
(Z)
balloon CO2
THF, 20 °C
Ph
O
Ph
1ba-E
O
Ph
O
24:76
80% yield in total
1ba-E
1ba-Z
Scheme 3. Stereochemical isomerization of the substrate with α-phenyl substitution.
866 | Bull. Chem. Soc. Jpn. 2015, 88, 862–870 | doi:10.1246/bcsj.20150043
© 2015 The Chemical Society of Japan

O
10 mol% Co(acac)2
4 eq. Et2Zn
O
TMSCHN2
N
N
balloon CO2
THF, 20 °C
O
O
O
OMe
O
1bb
5bb
24% yield
N
O
2bb
O
OM
Scheme 4. Employing the substrate with a triple bond.
catalytic amount of the cobalt complex and the combined use
of diethylzinc as the reducing agent realized the smooth reac-
tion process to give the desired product in moderate to excellent
yields at room temperature under atmospheric pressure of
carbon dioxide.
(0.25 mmol) and bis(acetylacetonato)cobalt(II) (conditions A:
3.2 mg, 5 mol %; conditions B: 6.4 mg, 10 mol %) was added a
1.0 M n-hexane solution of diethylzinc (conditions A: 0.5 mL,
2 equiv; conditions B: 1.0 mL, 4 equiv) at 0 °C, then the reac-
tion mixture was stirred at 20 °C for 1-48 h. After checking the
completed reaction by TLC analysis, the reaction mixture was
quenched with a 1.0 M hydrochloric acid diethyl ether solution
(conditions A: 1.5 mL, 6 equiv; conditions B: 3.0 mL, 12 equiv)
at 0 °C. The organic layer was extracted with diethyl ether,
washed with brine, dried over sodium sulfate and concentrated
in vacuum. The residue was purified by silica gel column chro-
matography (Hexanes:AcOEt:HCOOH = 1:1:0.003) to afford
the desired carboxylic acid 2. The resulting compound was
diluted with a mixed solution (6.25 mL, diethyl ether:MeOH =
5:1) and methylated with trimethylsilyldiazomethane in n-
hexane (ca. 0.6 M solution, (1.04 mL, 2.5 equiv)). After purifi-
cation by chromatography on silica gel, the corresponding
methyl carboxylate was isolated.
Experimental
1
General. The H and 13C NMR spectra were recorded on
a JEOL model AL-400, alpha-400, or ECX-400 spectrometer
using CDCl3 as the solvent. The IR spectra were measured on a
Thermo Electron Corporation model NICOLET 6700 FT-IR
spectrometer. The melting points were measured with a Stanford
Research Systems MPA100 or SHIMADZU DSC-60. The ESI
high resolution mass spectra were obtained using a Waters LCT
Premier XE mass spectrometer. Column chromatography was
conducted on silica gel (Kanto 60 N). The diethyl ether and
anhydrous THF were purchased from Kanto Chemical Co., Inc.,
and used without further purification. Carbon dioxide (99.5%)
was purchased from Sagami Acetylene Co., Ltd. Sodium sulfate
anhydrous, diethyl aluminum chloride in n-hexane (ca. 1.0 M
solution) and triethyl borane in n-hexane (ca. 1.0 M solution)
were purchased from Kanto Chemical Co., Inc., and used
without further purification. Diethylzinc in n-hexane (ca. 1.0 M
solution) was purchased from Tokyo Chemical Industry Co.,
Ltd., and repackaged into a smaller size to avoid degradation,
then used without further purification. Trimethylsilyldiazo-
methane in n-hexane (ca. 0.6 M solution) was purchased from
Tokyo Chemical Industry Co., Ltd., and used without further
purification. Unless otherwise noted, all reactor vessels and
syringes were dried by heating before use.
Synthesis of the Starting Materials. The starting materials
1a-1i and 1k-1m were synthesized from the corresponding
aldehydes by Wittig reaction or Horner-Wadsworth-Emmons
reaction. The corresponding aldehydes of the substrates 1b-1f
and 1h were prepared by a reported procedure.23 The corre-
sponding aldehyde of the substrate 1g was prepared by a
reported procedure.24 Cinnamonitrile 1j was purchased from
Tokyo Chemical Industry Co., Ltd., and purified by silica gel
column chromatography before use. The substrates 1n-1q were
synthesized from the butyrophenone or tetralone derivatives by
a reported procedure.25 The substrates 1r-1bb were synthe-
sized from the corresponding carboxylic acids via acid chloride
intermediates. The corresponding carboxylic acids of the sub-
strates 1r-1z, 1ac, 1ad, 1ag, 1aj, and 1ak were prepared from
aldehydes by reported procedure.26
2-Cyano-5-phenylpentanoate Methyl Ester (3a): Color-
1
less oil; H NMR (400 MHz, CDCl3): ¤ 1.76-1.90 (m, 2H),
1.93-2.03 (m, 2H), 2.69 (t, J = 7.6 Hz, 2H), 3.51 (t, J = 7.1 Hz,
1H), 3.81 (s, 3H), 7.16-7.23 (m, 3H), 7.30 (t, J = 7.6 Hz, 2H);
13C NMR (100 MHz, CDCl3): ¤ 28.3, 29.2, 34.9, 37.2, 53.4,
116.3, 126.1, 128.3, 128.5, 140.7, 166.6; IR (KBr): 2954, 2251,
1766, 1733, 1263, 1212, 751, 701; HRMS (ESI): [M + H]+
calcd for C13H16NO2+, 218.1176; found, m/z 218.1178.
Procedure for the Synthesis of 4p: Using the same pro-
cedure as previously described, to a THF solution of 1p (43.4
mg, 0.23 mmol) and the cobalt catalyst (10 mol %) was added a
1.0 M n-hexane solution of diethylzinc (1.0 mL, 4 equiv). After
methylation and purification, the ethyl-substituted product at
the β-position 4p was isolated (9.4 mg, 12%).
Methyl 1-Cyano-2-ethyl-6-methoxy-1,2,3,4-tetrahydro-
naphthalene-1-carboxylate (4p):
Colorless solid; mp:
120 °C; 1H NMR (400 MHz, CDCl3): ¤ 1.03 (t, J = 7.6 Hz,
3H), 1.60 (t, J = 7.3 Hz, 2H), 1.63-1.68 (m, 1H), 2.07-2.31 (m,
2H), 2.88 (dd, J = 8.3, 3.9 Hz, 2H), 3.78 (s, 3H), 3.88 (s, 3H),
6.66 (d, J = 2.4 Hz, 1H), 6.76 (dd, J = 8.5, 2.7 Hz, 1H), 7.14
(d, J = 8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): ¤ 11.6,
23.8, 25.4, 29.1, 43.0, 53.7, 54.4, 55.3, 113.6, 114.2, 118.2,
123.3, 128.9, 137.9, 159.7, 170.2; IR (KBr): 2935, 2238, 1736,
1609, 1263, 1035, 597; HRMS (ESI): [M + H]+ calcd for
C16H20NO3+, 274.1438; found, m/z 274.1433.
Methyl 2-Cyano-5-(p-tolyl)pentanoate (3b):
Colorless
1
oil; H NMR (400 MHz, CDCl3): ¤ 1.79-1.86 (m, 2H), 1.94-
2.00 (m, 2H), 2.32 (s, 3H), 2.64 (t, J = 7.6 Hz, 2H), 3.50
(t, J = 6.8 Hz, 1H), 3.80 (s, 3H), 7.05-7.12 (m, 4H); 13C NMR
(100 MHz, CDCl3): ¤ 21.0, 28.5, 29.3, 34.5, 37.3, 53.5,
General Procedure for the Reductive Carboxylation. In
a Schlenck flask filled with gaseous carbon dioxide, to a stirred
THF (1.5 mL) solution of the α,β-unsaturated compound 1
Bull. Chem. Soc. Jpn. 2015, 88, 862–870 | doi:10.1246/bcsj.20150043
© 2015 The Chemical Society of Japan | 867

+
116.3, 128.2, 129.2, 135.7, 137.6, 166.5; IR (KBr): 2928, 2250,
1750, 1259, 807, 543; HRMS (ESI): [M + H]+ calcd for
C14H18NO2+, 232.1333; found, m/z 232.1337.
730, 698; HRMS (ESI): [M + H]+ calcd for C13H16NO2
218.1176; found, m/z 218.1177.
Methyl
,
1-Cyano-1,2,3,4-tetrahydronaphthalene-1-
Methyl 2-Cyano-5-benzyloxypentanoate (3g): Colorless
oil; H NMR (400 MHz, CDCl3): ¤ 1.79-1.86 (m, 2H), 2.01-
carboxylate (3o): Colorless oil; 1H NMR (400 MHz, CDCl3):
¤ 1.98-2.07 (m, 2H), 2.38-2.53 (m, 2H), 2.87 (t, J = 6.0 Hz,
2H), 3.86 (s, 3H), 7.15-7.38 (m, 4H); 13C NMR (100 MHz,
CDCl3): ¤ 19.2, 28.4, 32.9, 47.6, 53.9, 120.1, 126.9, 128.7,
129.0, 129.7, 130.1, 136.6, 169.4; IR (KBr): 2954, 2241, 1736,
1240, 1099, 1017, 759; HRMS (ESI): [M + H]+ calcd for
C13H14NO2+, 216.1020; found, m/z 216.1023.
1
2.18 (m, 2H), 3.51-3.56 (m, 2H), 3.60 (dd, J = 8.3, 5.9 Hz,
1H), 3.81 (s, 3H), 4.50 (s, 2H), 7.28-7.38 (m, 5H); 13C NMR
(100 MHz, CDCl3): ¤ 26.8, 27.1, 37.1, 53.4, 68.8, 73.0, 116.5,
127.6, 127.7, 128.4, 138.1, 166.6; IR (KBr): 2955, 2864, 2250,
1747, 1259, 1101, 742, 699; HRMS (ESI): [M + H]+ calcd for
C14H18NO3+, 248.1282; found, m/z 248.1283.
Methyl 2-Cyano-4-phenylbutanoate (3i): Colorless oil;
1H NMR (400 MHz, CDCl3): ¤ 2.25-2.32 (m, 2H), 2.77-2.94
(m, 2H), 3.46 (t, J = 6.3 Hz, 1H), 3.79 (s, 3H), 7.20-7.34
(m, 5H); 13C NMR (100 MHz, CDCl3): ¤ 31.3, 32.6, 36.5,
53.5, 116.2, 126.8, 128.5, 128.8, 138.9, 166.5; IR (KBr): 2956,
2251, 1747, 1259, 750, 700; HRMS (ESI): [M + H]+ calcd for
C12H14NO2+, 204.1020; found, m/z 204.1024.
Methyl 1-Cyano-6-methoxy-1,2,3,4-tetrahydronaphtha-
1
lene-1-carboxylate (3p): Colorless oil; H NMR (400 MHz,
CDCl3): ¤ 1.92-2.08 (m, 2H), 2.35-2.50 (m, 2H), 2.84 (t, J =
6.3 Hz, 2H), 3.79 (s, 3H), 3.86 (s, 3H), 6.65 (d, J = 2.4 Hz,
1H), 6.79 (dd, J = 8.8, 2.4 Hz, 1H), 7.29 (d, J = 2.4 Hz, 1H);
13C NMR (100 MHz, CDCl3): ¤ 19.3, 28.8, 32.9, 47.1, 53.8,
55.3, 113.4, 114.3, 120.2, 121.8, 129.9, 138.1, 159.7, 169.6; IR
(KBr): 2955, 2240, 1743, 1609, 1244, 1124, 1038, 841; HRMS
(ESI): [M + H]+ calcd for C14H16NO2+, 246.1125; found, m/z
246.1129.
Methyl 2-Cyano-4-phenylpropanoate (3j):
Colorless
1
oil; H NMR (400 MHz, CDCl3): ¤ 3.17-3.32 (m, 2H), 3.72-
3.76 (m, 1H), 3.80 (s, 3H), 7.28-7.38 (m, 5H); 13C NMR (100
MHz, CDCl3): ¤ 35.7, 39.5, 53.6, 116.0, 127.8, 128.9, 129.0,
1-Ethyl 3-Methyl 2-(3-phenylpropyl)malonate (3r):
1
Colorless oil; H NMR (400 MHz, CDCl3): ¤ 1.24 (t, J = 7.3
135.2, 166.0; IR (KBr): 3032, 2957, 2252, 1743, 1267, 1213,
Hz, 3H), 1.61-1.69 (m, 2H), 1.95 (dd, J = 15.9, 7.6 Hz, 2H),
2.64 (t, J = 7.6 Hz, 2H), 3.36 (t, J = 7.6 Hz, 1H), 3.73 (s, 3H),
4.19 (q, J = 7.0 Hz, 2H), 7.16-7.30 (m, 5H); 13C NMR (100
MHz, CDCl3): ¤ 14.1, 28.4, 29.1, 51.8, 52.4, 61.4, 125.9,
128.2, 128.4, 141.7, 169.3, 169.9; IR (KBr): 2954, 1734, 1454,
1244, 1148, 1028, 750, 700; HRMS (ESI): [M + H]+ calcd for
C15H21O4+, 265.1434; found, m/z 265.1433.
+
750, 701; HRMS (ESI): [M + H]+ calcd for C11H12NO2
190.0863; found, m/z 190.0863.
,
Methyl 2-Cyano-2-methyl-5-phenylpentanoate (3k):
1
Yellow oil; H NMR (400 MHz, CDCl3): ¤ 1.58 (s, 3H), 1.68-
2.01 (m, 4H), 2.66 (t, J = 7.3 Hz, 2H), 3.81 (s, 3H), 7.16-7.32
(m, 5H); 13C NMR (100 MHz, CDCl3): ¤ 23.5, 27.0, 30.9, 35.2,
37.7, 43.7, 53.5, 119.9, 126.1, 128.3, 128.5, 140.9; IR (KBr):
2955, 2244, 1743, 1262, 751, 701; HRMS (ESI): [M + H]+
calcd for C14H18NO2+, 232.1333; found, m/z 232.1338.
Methyl 2-Cyano-3-methyl-5-phenylpentanoate (3l): Yel-
Methyl
noate (3t):
2-[Methyl(phenyl)carbamoyl]-5-phenylpenta-
Colorless oil; 1H NMR (400 MHz, CDCl3):
¤ 1.49-1.53 (m, 2H), 1.84-1.96 (m, 2H), 2.49-2.54 (m, 2H),
3.30 (s, 3H), 3.34 (dd, J = 8.3, 6.3 Hz, 1H), 3.66 (s, 3H), 7.10-
7.43 (m, 10H); 13C NMR (100 MHz, CDCl3): ¤ 29.1, 29.2,
35.6, 37.7, 49.0, 52.3, 125.8, 127.6, 128.2, 128.3, 128.4, 129.9,
141.9, 143.4, 169.0, 170.5; IR (KBr): 2950, 1747, 1661, 1453,
1383, 1201, 701, 563; HRMS (ESI): [M + H]+ calcd for
C20H24NO3+, 326.1751; found, m/z 326.1750.
1
low oil; diastereomers mixture; H NMR (400 MHz, CDCl3):
¤ 1.13 or 1.19 (d, J = 6.8 Hz, 3H), 1.67-1.86 (m, 2H), 2.26-
2.32 (m, 1H), 2.53-2.78 (m, 2H), 3.48 or 3.58 (d, J = 5.6 or
4.8 Hz, 1H), 3.79 or 3.81 (s, 3H), 7.16-7.32 (m, 5H); 13C NMR
(100 MHz, CDCl3): ¤ 16.4, 17.6, 32.9, 33.1, 34.0, 34.1,
34.8, 36.4, 43.6, 44.3, 53.3, 53.4, 115.1, 115.5, 126.1, 126.2,
128.3, 128.5, 128.6, 140.8, 166.2, 166.4; IR (KBr): 2933, 2249,
1747, 1257, 750, 701; HRMS (ESI): [M + H]+ calcd for
C14H18NO2+, 232.1333; found, m/z 232.1338.
Methyl 2-(4-Methoxybenzyl)-3-[methyl(phenyl)amino]-3-
oxopropanoate (3z):
Colorless oil; 1H NMR (400 MHz,
CDCl3): ¤ 3.03 (dd, J = 13.4, 5.1 Hz, 1H), 3.13-3.15 (m, 1H),
3.19 (s, 3H), 3.54 (dd, J = 10.3, 5.4 Hz, 1H), 3.70 (s, 3H), 3.81
(s, 3H), 6.79 (d, J = 8.8 Hz, 3H), 6.94 (d, J = 8.3 Hz, 2H),
7.27-7.29 (m, 4H); 13C NMR (100 MHz, CDCl3): ¤ 34.4, 37.4,
51.0, 52.4, 55.3, 113.7, 127.5, 128.0, 129.5, 130.2, 130.3,
143.2, 158.3, 168.5, 169.9; IR (KBr): 2953, 1747, 1655, 1513,
1442, 1248, 1035, 775, 549; HRMS (ESI): [M + H]+ calcd for
C19H22NO4+, 328.1543; found, m/z 328.1544.
Methyl 2-[Methyl(phenyl)carbamoyl]butanoate (3ae):
Yellow oil; 1H NMR (400 MHz, CDCl3): ¤ 0.83 (t, J = 7.3
Hz, 3H), 1.84-1.94 (m, 2H), 3.27 (t, J = 7.3 Hz, 1H), 3.32
(s, 3H), 3.67 (s, 3H), 7.23-7.46 (m, 5H); 13C NMR (100 MHz,
CDCl3): ¤ 11.9, 22.8, 37.6, 50.5, 52.2, 127.7, 128.2, 129.9,
143.5, 169.1, 170.5; IR (KBr): 2969, 1746, 1661, 1497, 1384,
1280, 1200, 1125, 776, 703, 563; HRMS (ESI): [M + H]+
calcd for C13H18NO3+, 236.1281; found, m/z 236.1281.
Methyl 2-(Morpholine-4-carbonyl)octanoate (3af): Yel-
low oil; 1H NMR (400 MHz, CDCl3): ¤ 0.85 (t, J = 7.1 Hz, 3H),
1.10-1.25 (br m, 8H), 1.79-1.89 (m, 2H), 3.31 (s, 3H), 3.33-
Methyl 2-Cyano-4-methyl-5-phenylpentanoate (3m):
Yellow oil; diastereomers mixture (diastereomer ratio =
1
53:47); H NMR (400 MHz, CDCl3): ¤ 0.95 or 0.96 (d, J =
6.0 or 7.2 Hz, 3H), 1.71-1.78 or 1.83-1.89 (m, 1H), 1.96-2.11
(m, 2H), 2.43-2.70 (m, 2H), 3.49-3.52 or 3.55-3.59 (m, 1H),
3.80 (s, 3H), 7.14-7.32 (m, 5H); 13C NMR (100 MHz, CDCl3):
¤ 18.4, 19.4, 32.6, 32.9, 35.6, 35.7, 36.1, 36.5, 42.6, 43.3, 53.5,
53.5, 116.2, 116.5, 126.3, 126.3, 128.4, 129.1, 139.5, 139.5,
166.7, 166.9; IR (KBr): 2956, 2249, 1747, 1251, 746, 702;
HRMS (ESI): [M + H]+ calcd for C14H18NO2+, 232.1333;
found, m/z 232.1339.
Methyl 2-Cyano-2-phenyl-pentanoate (3n): Yellow oil;
1H NMR (400 MHz, CDCl3): ¤ 0.97 (t, J = 7.2 Hz, 3H), 1.38-
1.53 (m, 2H), 2.07-2.14 (m, 1H), 2.32-2.39 (m, 1H), 3.79
(s, 3H), 7.35-7.43 (m, 3H), 7.54-7.56 (m, 2H); 13C NMR (100
MHz, CDCl3): ¤ 13.7, 18.9, 40.2, 53.9, 54.1, 118.4, 126.0,
128.8, 129.1, 134.5, 168.3; IR (KBr): 2964, 2245, 1751, 769,
868 | Bull. Chem. Soc. Jpn. 2015, 88, 862–870 | doi:10.1246/bcsj.20150043
© 2015 The Chemical Society of Japan

3.35 (m, 1H), 3.67 (s, 3H), 7.23 (d, J = 8.3 Hz, 2H), 7.35-7.46
(m, 3H); 13C NMR (100 MHz, CDCl3): ¤ 14.0, 22.5, 27.3, 29.0,
29.5, 31.5, 37.7, 49.0, 52.2, 127.6, 128.2, 129.8, 143.5, 169.2,
170.7; IR (KBr): 2927, 2857, 1747, 1663, 1596, 1496, 1383,
1261, 1117, 1027, 775, 702, 563; HRMS (ESI): [M + H]+ calcd
for C17H26NO3+, 292.1907; found, m/z 292.1904.
Methyl 2-Methyl-2-[methyl(phenyl)carbamoyl]butanoate
(3au): Colorless oil; 1H NMR (400 MHz, CDCl3): ¤ 0.83
(t, J = 7.6 Hz, 3H), 1.34 (s, 3H), 1.80 (br s, 2H), 3.24 (s, 3H),
3.50 (br s, 3H), 7.16-7.40 (m, 5H); 13C NMR (100 MHz,
CDCl3): ¤ 8.5, 21.7, 29.8, 40.2, 51.8, 53.9, 128.3, 128.3, 128.8,
129.2, 171.1, 173.8; IR (KBr): 2948, 1736, 1655, 1496, 1455,
1361, 1243, 1146, 776, 704, 575; HRMS (ESI): [M + H]+
calcd for C14H20NO3+, 250.1438; found, m/z 250.1435.
Methyl 2-Methyl-2-(morpholine-4-carbonyl)butanoate
(3av): Colorless oil; 1H NMR (400 MHz, CDCl3): ¤ 0.87
(t, J = 7.6 Hz, 3H), 1.40 (s, 3H), 1.80-2.02 (m, 2H), 3.62-3.64
(br m, 8H), 3.74 (s, 3H); 13C NMR (100 MHz, CDCl3): ¤ 8.5,
20.9, 29.6, 52.4, 52.6, 66.6, 169.9, 174.9; IR (KBr): 2974,
2857, 1422, 1302, 1251, 1117, 1040, 858, 593; HRMS (ESI):
[M + H]+ calcd for C11H20NO4+, 230.1387; found, m/z
230.1387.
Methyl 2-(4-Methoxybenzyl)-3-morpholino-3-oxopropa-
noate (3ag):
Colorless oil; 1H NMR (400 MHz, CDCl3):
¤ 3.19-3.23 (m, 4H), 3.40-3.65 (m, 6H), 3.72 (s, 3H), 3.78
(s, 3H), 3.82 (t, J = 7.6 Hz, 1H), 6.80-6.83 (m, 2H), 7.10-7.13
(m, 2H); 13C NMR (100 MHz, CDCl3): ¤ 34.3, 42.5, 46.5, 50.2,
52.5, 55.2, 66.3, 66.6, 113.9, 130.0, 130.1, 158.4, 166.9, 169.7;
IR (KBr): 2957, 2858, 1743, 1641, 1514, 1437, 1247, 1114,
1033, 918, 847, 757, 564; HRMS (ESI): [M + H]+ calcd for
C16H22NO5+, 308.1492; found, m/z 308.1493.
Methyl 2-(Morpholine-4-carbonyl)butanoate (3al): Col-
1
orless oil; H NMR (400 MHz, CDCl3): ¤ 0.96 (t, J = 7.3 Hz,
Methyl 2-(Morpholine-4-carbonyl)hexanoate (5bb):
1
3H), 1.98 (dq, J = 17.1, 7.3 Hz, 2H), 3.45-3.69 (m, 9H), 3.73
(s, 3H); 13C NMR (100 MHz, CDCl3): ¤ 12.1, 22.5, 42.6, 46.4,
50.4, 52.4, 66.6, 66.8, 167.1, 170.3; IR (KBr): 2969, 2859,
1743, 1636, 1437, 1271, 1116, 1034, 865, 571; HRMS (ESI):
[M + H]+ calcd for C10H18NO4+, 216.1230; found, m/z
216.1226.
Colorless oil; H NMR (400 MHz, CDCl3): ¤ 0.90 (t, J = 7.1
Hz, 3H), 1.26-1.37 (m, 4H), 1.90-1.98 (m, 2H), 3.51-3.72 (m,
9H), 3.73 (s, 3H); 13C NMR (100 MHz, CDCl3): ¤ 13.9, 22.5,
28.8, 29.7, 42.6, 46.4, 48.8, 52.5, 66.6, 66.8, 167.3, 170.4;
IR (KBr): 3489, 2959, 2922, 2858, 1736, 1647, 1435, 1253,
1116, 1033; HRMS (ESI): [M + H]+ calcd for C12H22NO4
244.1543; found, m/z 244.1544.
,
+
Methyl 2-(Morpholine-4-carbonyl)octanoate (3am):
1
Colorless oil; H NMR (400 MHz, CDCl3): ¤ 0.87 (t, J = 6.8
Supporting Information
Hz, 3H), 1.28 (s, 8H), 1.93 (s, 2H), 3.45-3.68 (m, 9H), 3.73
(s, 3H); 13C NMR (100 MHz, CDCl3): ¤ 14.0, 22.5, 27.5, 29.0,
29.1, 31.5, 42.6, 46.4, 48.9, 52.5, 66.6, 66.8, 167.3, 170.4; IR
(KBr): 3478, 2925, 2857, 1743, 1648, 1436, 1271, 1116, 1029;
HRMS (ESI): [M + H]+ calcd for C14H26NO4+, 272.1856;
found, m/z 272.1858.
1
The material data, the H NMR, 13C NMR spectra data of
the substrates and products are provided. These materials are
available free of charge on J-STAGE.
References
Methyl 2-Benzyl-3-[benzyl(methyl)amino]-3-oxopropa-
noate (3an): Colorless oil; regioisomers mixture; H NMR
1
1011.
2
T. Mukaiyama, K. Narasaka, K. Banno, Chem. Lett. 1973,
1
(400 MHz, CDCl3): ¤ 2.77 or 2.90 (s, 3H), 3.21-3.37 (m, 2H),
3.70 or 3.74 (d, J = 1.0 Hz, 3H), 3.88 or 3.99 (dd, J = 8.9,
6.0 Hz, 1H), 4.25-4.71 (m, 2H), 6.86-7.27 (m, 10H); 13C NMR
(100 MHz, CDCl3): ¤ 25.6, 34.3, 35.1, 35.4, 50.6, 50.8,
51.2, 52.5, 52.5, 53.3, 99.6, 126.2, 126.6, 127.3, 127.5, 127.8,
128.5, 128.5, 128.8, 129.0, 129.2, 135.9, 136.6, 138.4, 155.9,
a) Y. Ito, M. Sawamura, T. Hayashi, J. Am. Chem. Soc.
1986, 108, 6405. b) G. A. Slough, R. G. Bergman, C. H.
Heathcock, J. Am. Chem. Soc. 1989, 111, 938. c) J. Nokami, T.
Mandai, H. Watanabe, H. Ohyama, J. Tsuji, J. Am. Chem. Soc.
1989, 111, 4126. d) T. Naota, H. Taki, M. Mizuno, S. Murahashi,
J. Am. Chem. Soc. 1989, 111, 5954.
3
a) E. M. Carreira, R. A. Singer, W. Lee, J. Am. Chem. Soc.
168.4, 169.8; IR (KBr): 3029, 2952, 1746, 1648, 1454, 1266,
+
753, 700; HRMS (ESI): [M + H]+ calcd for C19H22NO3
312.1594; found, m/z 312.1593.
,
1994, 116, 8837. b) M. Sodeoka, K. Ohrai, M. Shibasaki, J. Org.
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Methyl 2-Methyl-3-[Methyl(phenyl)amino]-3-oxo-2-phen-
4
5
S. Isayama, T. Mukaiyama, Chem. Lett. 1989, 2005.
a) T. Mukaiyama, S. Isayama, S. Inoki, K. Kato, T. Yamada,
ylpropanoate (3aq):
Colorless oil; 1H NMR (400 MHz,
CDCl3): ¤ 1.74 (br s, 3H), 3.24 (br s, 3H), 3.70 (s, 3H), 6.59
(s, 1H), 7.01-7.52 (m, 9H); 13C NMR (100 MHz, CDCl3):
¤ 27.5, 40.1, 52.3, 58.7, 126.5, 126.9, 127.5, 127.8, 128.1,
128.3, 128.8, 129.5, 170.9, 172.2; IR (KBr): 3002, 2950, 1740,
1655, 1447, 1372, 1247, 1198, 1106, 766, 699, 539; HRMS
(ESI): [M + H]+ calcd for C18H20NO3+, 298.1438; found, m/z
298.1439.
T. Takai, Chem. Lett. 1989, 449. b) K. Kato, T. Yamada, T. Takai,
S. Inoki, S. Isayama, Bull. Chem. Soc. Jpn. 1990, 63, 179.
6
T. Nagata, K. Yorozu, T. Yamada, T. Mukaiyama, Angew.
Chem., Int. Ed. Engl. 1995, 34, 2145.
T. Yamada, T. Nagata, K. D. Sugi, K. Yorozu, T. Ikeno, Y.
7
Ohtsuka, D. Miyazaki, T. Mukaiyama, Chem.®Eur. J. 2003, 9,
4485.
Methyl
noate (3ar):
2-Methyl-3-morpholino-3-oxo-2-phenylpropa-
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870 | Bull. Chem. Soc. Jpn. 2015, 88, 862–870 | doi:10.1246/bcsj.20150043
© 2015 The Chemical Society of Japan