Enantioselective conjugate addition of both aromatic ketones and acetone to nitroolefins catalyzed by chiral primary amines bearing multiple hydrogen-bonding donors

Article abstract of DOI:10.1021/jo300011x

A new class of chiral primary amine catalysts bearing multiple hydrogen-bonding donors have been designed and synthesized. The newly developed bifunctional organocatalysts efficiently catalyzed not only enantioselective conjugate addition of aromatic keto

Full text of DOI:10.1021/jo300011x

Note
pubs.acs.org/joc
Enantioselective Conjugate Addition of Both Aromatic Ketones and
Acetone to Nitroolefins Catalyzed by Chiral Primary Amines Bearing
Multiple Hydrogen-Bonding Donors
Zhong-Wen Sun,† Fang-Zhi Peng,*,† Ze-Qian Li,† Li-Wei Zou,† Shao-Xiong Zhang,† Xiang Li,†
and Zhi-Hui Shao*,†,‡
†Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology,
Yunnan University, Kunming 650091, China
‡State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China
S
* Supporting Information
ABSTRACT: A new class of chiral primary amine catalysts bearing multiple hydrogen-bonding donors have been designed and
synthesized. The newly developed bifunctional organocatalysts efficiently catalyzed not only enantioselective conjugate addition
of aromatic ketones to nitroolefins in good yields (up to 87%) with excellent enantioselectivities (97→99% ee) but also
enantioselective conjugate addition of acetone to nitroolefins in excellent yields (90−96%) with high enantioselectivities (up to
97% ee).
esign of new chiral organocatalysts to meet the needs of
challenging asymmetric transformations is one of the
interested in the development of a new class of general chiral
organic catalysts to realize these two most challenging reactions
in this field.
Recently, chiral multifunctional organocatalysts bearing
multiple hydrogen-bonding donors have emerged as promising
catalysts for asymmetric transformations.12 Notably, Wang’s
group has recently developed a new class of bifunctional tertiary
amine−thioureas bearing multiple hydrogen bonding donors
for several catalytic asymmetric reactions via noncovalent
catalysis (Scheme 1).13 Inspired by this seminal work, and
D
most important undertakings in current asymmetric organo-
catalysis.1 Direct conjugate addition of carbonyl compounds to
nitroolefins represents a convenient access to bifunctional chiral
nitroalkanes, which are valuable building blocks in organic
synthesis and medicinal chemistry, and development of the
chiral catalysts for such processes has received much attention.2
Over the past years, impressive progress has been made in the
development of metal-free organic catalysts for the enantiose-
lective addition of 1,3-dicarbonyl compounds,3 aldehydes,4 and
cyclic ketones5 to nitroolefins. Nonetheless, the direct catalytic
asymmetric conjugate addition of aromatic ketones to nitro-
olefins and the catalytic asymmetric conjugate reaction between
acetone and nitroolefins remain the two most important
challenges in this field.
Scheme 1. Two Types of Catalytic Modes in Organocatalysis
Since the pioneering and independent work by Tsogoeva,6
Jacobsen,7 and Ma,8 a few bifunctional chiral primary amines
have been developed as effective organocatalysts for the
asymmetric conjugate addition of acetone to nitroolefins9 and
the asymmetric conjugate reaction between aromatic ketones
and nitroolefins,10 respectively. However, despite these limited
cases, few general catalyst systems with broad substrate scope
have been reported for the asymmetric conjugate addition of
both aromatic aromatic ketones and acetone to nitroolefins
with enantiomeric excesses of over 90%.11 Thus, we became
considering the importance and challenge of the direct catalytic
asymmetric conjugate addition of both aromatic ketones and
acetone to nitroolefins, together with our interest in chiral
primary amine catalysis,14 we envisioned that chiral primary
amines bearing multiple hydrogen-bonding donors might serve
Received: January 6, 2012
Published: March 23, 2012
© 2012 American Chemical Society
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Note
Figure 1. New class of chiral primary amine catalysts.
Scheme 2. Synthesis of Chiral Primary Amine Catalysts Bearing Multiple Hydrogen-Bonding Donors
as a new class of easily tunable bifunctional organic catalysts for
the enantioselective conjugate addition of both aromatic
ketones and acetone to nitroolefins.
protecting group from nitrogen with trifluoroacetic acid
afforded the target catalysts 1e,f.
With these catalysts in hand, we initially investigated the
more challenging asymmetric conjugate addition of aromatic
ketones to nitroolefins. Acetophenone 11a and β-nitrostyrene
12a were selected as the model substrates for initial
optimization studies. To our delight, the newly designed
catalysts 1a prompted the desired reaction, providing the
desired product 13a in 72% yield and >99% ee (Table 1, entry
1). Interestingly, its diastereoisomer 1b afforded the same level
of asymmetric induction but moderate yield (entry 2). This
seems to indicate that the (R,R)-1,2-diphenylethenediamine
moiety matched the (R,R)-cyclohexanediamine moiety, and the
configuration of the product was determined mainly by the
latter, but the catalytic activity could be greatly enhanced by the
former. Replacing the Ts group of 1a with a less bulky group
(Ms) decreased the catalytic activity significantly (26% yield)
(entry 3). In order to investigate the effects of the chiral
diamine scaffolds on the catalytic activities, the α-amino acid
derived chiral primary amine catalysts bearing multiple
hydrogen-bonding donors 1e,f were evaluated. These catalysts
promoted the desired reaction in moderate selectivity (entries 5
As part of our interest in asymmetric organocatalysis,14,15
herein we report a new class of general chiral primary amine
catalysts bearing multiple hydrogen bonding donors which
efficiently catalyzed enantioselective conjugate addition of
aromatic ketones to nitroolefins and enantioselective conjugate
reaction of acetone to nitroolefins which are two of the most
challenging reactions in this field in good yields (up to 96%)
with high to excellent enantioselectivities (up to >99% ee).
Designed chiral primary amine catalysts bearing multiple
hydrogen-bonding donors (Figure 1) were readily synthesized
by the following procedures described in Scheme 2. The
organocatalysts 1a−d were prepared from monoprotected
chiral diamine 316 in three steps. The preparation of chiral
primary amine catalysts 1e,f started with α-amino acids 7. The
treatment of Boc-protected chiral diamine 817 with CS2/Et3N/
TsCl provided the corresponding isothiocyanates 9.18 Then the
condensation of isothiocyanates 3 with the amine 5 in DCM
gave the corresponding thioureas 10. Removing the Boc
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Note
a
Table 1. Conjugate Addition of Acetophenone to β-Nitrostyrene
b
c
entry
catalyst
solvent
additive
yield (%)
ee (%)
1
2
1a
1b
1c
1d
1e
1f
DCM
DCM
DCM
DCM
DCM
DCM
CHCl3
DCE
PhCO2H
72
50
>99
>99
>99
>99
76
PhCO2H
3
PhCO2H
26
4
PhCO2H
27
5
PhCO2H
30
6
PhCO2H
22
72
7
1a
1a
1a
1a
1a
1a
1a
1a
PhCO2H
60
>99
95
8
PhCO2H
14
9
THF
PhCO2H
14
97
10
11
12
13
14
toluene
DCM
DCM
DCM
DCM
PhCO2H
45
97
4-NO2C6H4CO2H
4-MeOC6H4CO2H
PhCO2H
32
>99
>99
58
d
61
>99
none
trace
N.D.
a
Reactions carried out on a 0.2 mmol scale. General conditions: β-nitrostyrene (0.2 mmol), acetophenone (0.6 mmol), PhCO2H (0.03 mmol), and
b
c
catalyst (15 mol %) were stirred in 0.2 mL of solvent at rt for 96 h. Isolated yield. Enantiomeric excess (ee) was determined by HPLC analysis
using a chiral stationary phase. 5 mol % of PhCO2H was used.
d
a
Table 2. Conjugate Addition of Aromatic Ketones to Nitroolefins
b
c
entry
Ar
R
13
yield (%)
ee (%)
1
2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
13a
13b
13c
13d
13e
13f
72
75
73
81
87
80
75
72
71
77
71
80
79
83
71
>99
98
4-Me-C6H4
3
4-MeO-C6H4
98
4
4-NO2-C6H4
>99
98
5
4-CF3-C6H4
6
4-Br-C6H4
98
7
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4-Me-C6H4
4-MeO-C6H4
4-Cl-C6H4
4-Br-C6H4
2-Br-C6H4
4-CF3-C6H4
3-CF3-C6H4
2-CF3-C6H4
2-furyl
13g
13h
13i
>99
>99
>99
>99
99
8
9
10
11
12
13
14
15
13j
13k
13l
97
13m
13n
13o
98
>99
98
a
Reactions carried out on a 0.2 mmol scale. General conditions: nitroolefin (0.2 mmol), aromatic ketone (0.6 mmol), PhCO2H (0.03 mmol), and
b
c
catalyst (15 mol %) were stirred in 0.2 mL of CH2Cl2 at rt for 96 h. Isolated yield. Enantiomeric excess (ee) was determined by HPLC analysis
using a chiral stationary phase.
and 6); however, this represents the first example of chiral
primary amine−thiourea-type catalysts derived from acyclic α-
amino acids. In order to evaluate the role the multiple
hydrogen-bonding donors played in this system, a control
experiment was performed with the catalyst 1d in which the
sulfonamide NMeSO2Ts was methylated. The use of the
catalyst 1d led to poor catalytic activity (27% yield after 96 h)
(entry 4). This indicates that the third NH of sulfonamide on
the 1,2-diphenylethenediamine moiety played a significant role
in this conjugate addition reaction.
of ClCH2CH2Cl led to the conjugate adduct in only 14% yield
(entry 8).
The presence of acid additives was also crucial for the
reaction to occur. Without any additive, the reaction became
sluggish (entry 14). Among the acids examined, benzoic acid
was found to be the best additive.
Under the optimized reaction conditions, the substrate scope
with respect to both aromatic ketones and nitroolefins was
examined. As shown in Table 2, the reaction has a broad
substrate scope with respect to both aromatic ketones and
nitroolefins. A wide range of electron-rich and electron-
deficient aromatic ketones underwent smoothly the conjugate
addition reactions of β-nitrostyrene in good yield (73−87%)
The solvents have a remarkable effect on the catalytic activity
(entry 1 and entries 7−10). The chlorocarbon solvents seem to
be promising (entries 1 and 7). Interestingly, however, the use
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Note
with excellent enantioselectivities (98→99% ee) (entries 2−6,
Table 2). With regard to nitroolefins, it appears that the
position and the electronic property of the substituents for
aromatic rings of nitroalkenes are well tolerated by the
conjugate addition reactions. Whether electron-withdrawing
(entries 9−14, Table 2), -donating (entries 7−8, Table 2), or
-neutral (entry 1, Table 2) groups on aromatic rings were used,
the reactions proceeded smoothly to give the desired adducts in
good yields (71−83%) with excellent enantioselectivities (97→
99% ee). Moreover, a heteroaromatic nitroolefin was also a
suitable substrate for this nitro-Michael addition (entry 15).19
Notably, the products of the Michael addition of aromatic
ketones are useful intermediates for a variety of further
elaborated structures such as chiral pyrrolidines,10a γ-lactams,
and γ-amino acids.20 For example, the product 13i can be
transformed into the therapeutically useful GABAB receptor
agonist (R)-baclofen hydrochloride through a three-step route
involving Baeyer−Villiger oxidation followed by reduction and
subsequent hydrolysis.20
to investigate the direct conjugate addition of acetone to
nitroolefins with the chiral catalyst 1a. Acetone is still one of
the most problematic substrates for the nitro-Michael addition.
Acetone and β-nitrostyrene 12a were selected as the model
substrates in the preliminary screening. In the presence of 15
mol % of catalyst 1a and DCM as solvent, the desired conjugate
prodcut 14a was obtained in 90% yield and 84% ee. Then we
investigated the effects of the solvents on the conjugate
reaction. As summarized in Table 3, the use of CHCl3 led to
the best results (92% yield, 96% ee, entry 2). The acid additives
were also examined. Among the acid additives examined,
PhCO2H was still the optimal additive.
With the optimized reaction conditions in hand, the scope of
the reaction was investigated (Table 4). It appears that the
position and the electronic property of the substituents for
aromatic rings of nitroolefins have little effects on the conjugate
addition. A wide range of nitroolefins underwent the conjugate
addition reactions of acetone in high yields (90−96%) with
good enantioselectivities (84−97% ee) (entries 1−8).
In summary, we have developed a new class of easily tunable
chiral primary amine catalysts bearing multiple hydrogen-
bonding donors. These chiral primary amines as general
catalysts efficiently catalyzed enantioselective conjugate addi-
tion of aromatic ketones to nitroolefins and conjugate reaction
of acetone to nitroolefins, which are two of the most
challenging reactions in this field in good to excellent yields
and high to excellent enantioselectivities. The corresponding
products are useful intermediates for a variety of further
elaborated structures such as chiral pyrrolidines, γ-lactams, and
γ-amino acids.
To gain insight into the reaction mechanism, we performed
the reaction between acetophenone 11a and β-nitrostyrene 12a
with Wang’s catalyst. The catalytic asymmetric Michael
addition did not occur after 96 h (eq 1).
EXPERIMENTAL SECTION
■
1H NMR and 13C NMR spectra were recorded on a 300 MHz
spectrophotometer. Chemical shifts (δ) are expressed in ppm, and J
values are given in Hz. The enantiomeric excess was determined by
HPLC using Chiralpak AD-H and Chiralpak AS-H columns with n-
hexane and 2-propanol as eluents. High-resolution mass spectrometry
(HRMS) was recorded on a spectrometer. Optical rotations were
measured on a polarimeter. Flash column chromatography was
performed on silica gel (230−400 mesh). All chemicals and solvents
were used as received without further purification unless otherwise
stated.
On the basis of the above results, a bifunctional mechanism
involving hydrogen bonding and enamine formation has been
proposed to account for the enantioselectivity observed (Figure
2). The primary amine activates the aromatic ketone through
Preparation of Chiral Primary Amines 1a−d. The isothiocya-
nate 416 (1.0 mmol) and the amine 5 (1.0 mmol) were placed in a 25
mL vial equipped with a Teflon-coated stir bar. Dry CH2Cl2 (10 mL)
was added. The resulting solution was stirred at room temperature
overnight until the reaction was complete (monitored by TLC). After
removal of the solvent, the crude product was dissolved in MeOH (2
mL), and N2H4·H2O (5 mmol) was added. The resulting mixture was
stirred under reflux until the reaction was complete (monitored by
TLC). After filtration, the filtrate was evaporated under vacuum and
purified through column chromatography on silica gel (petroleum
ether/ethyl acetate as the eluents) to afford the desired catalyst 1a−d
as a white solid.
Data for 1a. Amorphous solid, 408 mg, 78% yield. [α]20D = +114.7
Figure 2. Proposed transition-state model for the Michael addition of
aromatic ketones with β-nitrostyrene.
1
(c 1.0 CHCl3). H NMR (300 MHz, CD3OD): δ = 7.88 (s, 2H),
7.42−7.45 (d, J = 8.4 Hz, 2H), 7.11 (s, 3H), 7.04−7.07(d, J = 7.5 Hz,
4H), 6.94−7.01 (dd, J = 6.3, 5.7 Hz, 3H), 6.85−6.87 (d, J = 6.3 Hz,
2H), 5.79−5.82 (d, J = 9.9 Hz, 1H), 4.62−4.65 (d, J = 9.9 Hz, 1H),
4.06−4.13 (dd, J = 7.2, 7.2 Hz, 1H), 2.50 (s, 1H), 2.27 (s, 3H), 1.95−
2.00 (m, 3H), 1.73 (s, 2H), 1,07−1.33 (m, 6H). 13C NMR (75 MHz,
CD3OD): δ = 184.5, 144.2, 140.1, 139.9, 139.5, 130.3, 129.4, 129.1,
129.0, 128.9, 128.7, 128.5, 127.8, 65.0, 63.8, 61.1, 56.5, 34.6, 33.0, 26.1,
25.9, 21.4. HRMS: calcd for C28H35N4O2S2 [M]+ 523.2201, found
523.2217.
the formation of an enamine intermediate promoted by the acid
additive, while the multiple hydrogen-bonding functionality
interacts with the nitro group to enhance the electrophilicity of
nitroolefin.
Having proven excellent stereocontrol performance of the
chiral primary amine catalyst 1a, we next turned our attention
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Note
a
Table 3. Conjugate Addition of Acetone to Nitrostyrene
b
c
entry
solvent
additive
yield (%)
ee (%)
1
2
DCM
PhCO2H
90
92
84
CHCl3
DCE
PhCO2H
96
3
PhCO2H
85
95
4
toluene
m-xylene
Et2O
PhCO2H
77
80
5
PhCO2H
75
86
6
PhCO2H
68
88
7
THF
PhCO2H
80
75
8
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CH3CO2H
CF3CO2H
4-NO2C6H4CO2H
4-MeOC6H4CO2H
PhOH
93
92
9
trace
84
N.D.
88
10
11
12
89
90
trace
N.D.
a
Reactions carried out on a 0.2 mmol scale. General conditions: nitroolefin (0.2 mmol), acetone (2 mmol), PhCO2H (0.03 mmol), and catalyst (15
b
c
mol %) were stirred in 0.2 mL of solvent at rt for 72 h. Isolated yield. Enantiomeric excess (ee) was determined by HPLC analysis using a chiral
stationary phase.
a
Table 4. Conjugate Addition of Acetone to Various Nitroolefins
b
c
entry
R
14
yield (%)
ee (%)
1
2
3
4
5
6
7
8
Ph
14a
14b
14c
14d
14e
14f
92
90
91
94
93
92
91
96
96
97
93
96
93
90
84
94
4-Me-C6H4
4-MeO-C6H4
4-Br-C6H4
4-Cl-C6H4
2-Br-C6H4
3-CF3-C6H4
2-furyl
14g
14h
a
Reactions carried out on a 0.2 mmol scale. General conditions: nitroolefin (0.2 mmol), acetone (2 mmol), PhCO2H (0.03 mmol), and catalyst (15
b
c
mol %) were stirred in 0.2 mL of CHCl3 at rt for 72 h. Isolated yield. Enantiomeric excess (ee) was determined by HPLC analysis using a chiral
stationary phase.
Data for 1b. Amorphous solid, 397 mg, 76% yield. [α]20
=
3H), 2.02−2.03 (d, J = 4.5 Hz, 2H), 1.19 (s, 1H), 1.78 (s, 2H), 0.99−
1.35 (m, 5H). 13C NMR (75 MHz, CD3OD): δ = 184.1, 144.9, 140.8,
138.4, 135.9, 130.7, 130.6, 129.5, 129.4, 129.2, 128.6, 128.4, 65.9, 59.7,
58.7, 56.2, 33.6, 33.1, 31.3, 25.9, 25.6, 21.5. HRMS: calcd for
C29H37N4O2S2 [M]+ 537.2357, found 537.2347.
D
1
−153.3 (c 1.0 CHCl3). H NMR (300 MHz, CD3OD): δ = 7.88 (s,
2H), 7.42−7.45 (d, J = 8.4 Hz, 2H), 7.11 (s, 3H), 7.04−7.07 (d, J = 7.5
Hz, 4H), 6.94−7.01 (dd, J = 6.3, 5.7 Hz, 3H), 6.85−6.87 (d, J = 6.3
Hz, 2H), 5.79−5.82 (d, J = 9.9 Hz, 1H), 4.62−4.65 (d, J = 9.9 Hz,
1H), 4.06−4.13 (dd, J = 7.2, 7.2 Hz, 1H), 2.50 (s, 1H), 2.27 (s, 3H),
1.95−2.00 (m, 3H), 1.73 (s, 2H), 1,07−1.33 (m, 6H). 13C NMR (75
MHz, CD3OD): δ = 184.5, 144.2, 140.1, 139.9, 139.5, 130.3, 129.4,
129.1, 129.0, 128.9, 128.7, 128.5, 127.8, 65.0, 63.8, 61.1, 56.5, 34.6,
33.0, 26.1, 25.9, 21.4. HRMS: calcd for C28H35N4O2S2 [M]+ 523.2201,
found 523.2217.
Preparation of Chiral Primary Amines 1e,f. The isothiocyanate
918 (1.0 mmol) and the amine 5 (1.0 mmol) were placed in a 50 mL
vial equipped with a Teflon-coated stir bar. Dry CH2Cl2 (10 mL) was
added. The resulting solution was stirred at room temperature
overnight until the reaction was complete (monitored by TLC). After
removal of the solvent, the crude product was dissolved in CH2Cl2 (20
mL), and CF3CO2H (9 mL) was added dropwise at 0 °C. The
resulting mixture was stirred under at room temperature until the
reaction was complete (monitored by TLC). The reaction mixture was
evaporated under vacuum. The resulting residue was extracted with
CH2Cl2, and the separated organic phase was washed by saturated
aqueous NaHCO3. The combined organic phase was dried over
anhydrous Na2SO4. After removal of solvent, the crude product was
purified through column chromatography on silica gel (petroleum
ether/ethyl acetate as the eluents) to afford the desired catalysts 1e,f.
Data for 1e. Amorphous solid, 380 mg, 68% yield. [α]20D = +26.5
(c 1.0 CHCl3). 1H NMR (300 MHz, CD3OD): δ = 7,49−7.51 (d, J =
7.5 Hz, 2H), 7.21−7.29 (m, 6H), 7.03−7.09 (m, 8H), 6.93−6.97 (m,
5H), 5.79−5.81 (d, J = 6.9 Hz, 1H), 4.69−4.72 (d, J = 9.3 Hz, 1H),
Data for 1c. Amorphous solid, 317 mg, 71% yield. [α]20D = +81.2
1
(c 0.9 CHCl3). H NMR (300 MHz, CD3OD): δ = 7.90 (s, 1H),
7.17−7.21 (d, J = 13.8 Hz, 10H), 5.85−5.87 (d, J = 8.7 Hz, 1H), 4.80−
4.83 (d, J = 9.9 Hz, 2H), 4.10 (s, 1H), 2.71 (s, 3H), 2.56 (s, 1H), 1.98
(s, 2H), 1,74 (s, 2H), 1.12−1.30 (m, 5H). 13C NMR (75 MHz,
CD3OD): δ = 184.4, 140.6, 140.1, 129.6, 129.4, 129.2, 129.1, 128.9,
128.7, 64.7, 63.8, 61.0, 56.1, 41.9, 34.6, 33.1, 26.0, 25.8. HRMS: calcd
for C22H31N4O2S2 [M]+ 447.1888, found 447.1893.
Data for 1d. Amorphous solid, 403 mg, 75% yield. [α]20D = +51.4
(c 0.4 CHCl3). 1H NMR (300 MHz, CD3OD): δ = 7.60−7.62 (d, J =
7.5 Hz, 2H), 7.33−7.35 (d, J = 7.8 Hz, 2H), 7.25−7.27 (d, J = 7.8 Hz,
2H), 7.08−7.18 (m, 8H), 6.44−6.48 (d, J = 11.4 Hz, 1H), 5.50−5.51
(d, J = 11.4 Hz, 1H), 4.25 (s, 1H), 2.85 (s, 3H), 2.72 (s, 1H), 2.37 (s,
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1H NMR (300 MHz, CDCl3): δ = 7.75−7.78 (d, J = 8.4 Hz, 2H),
7.57−7.60 (d, J = 8.7 Hz, 2H), 7.26−7.36 (m, 5H), 4.78−4.84 (dd, J =
6.9, 6.9 Hz, 1H), 4.65−4.71 (dd, J = 7.8, 7.8 Hz, 1H), 4.16−4.25 (m,
1H), 3.34−3.49 (m, 2H). 13C NMR (75 Hz, CDCl3): δ = 195.9, 138.9,
132.1, 129.5, 129.1, 128.8, 128.0, 127.4, 79.5, 41.5, 39.2. HPLC
(Chiralpak AD-H, 2-propanol/hexane = 15/85, flow rate 1.0 mL/min,
λ = 254 nm): tmajor = 18.6 min, tminor = 24.4 min.
3.67 (s, 1H), 3.37−3.41 (d, J = 12.6 Hz, 1H), 3.29−3.32 (d, J = 11.1
Hz, 1H), 2.76−2.79 (d, J = 8.1 Hz, 1H), 2.56−2.62 (d, J = 7.2 Hz,
1H), 2.24 (s, 3H). 13C NMR (75 MHz, CD3OD): δ = 184.9, 144.2,
139.9, 139.7, 139.6, 139.5, 130.5, 130.4, 129.8, 129.5, 129.1, 129.0,
128.8, 128.5, 128.0, 127.8, 65.1, 64.1, 53.7, 50.5, 41.7, 21.7. HRMS:
calcd for C31H34N4O2S2 [M]+ 558.2123, found 558.2092.
Data for 1f. Amorphous solid, 343 mg, 63% yield. [α]20 = +27.0
D
(c 1.0 CHCl3). 1H NMR (300 MHz, CD3OD): δ = 7.47−7.50 (d, J =
7.8 Hz, 2H), 7.18−7.41 (m, 6H), 6.79−7.10 (m, 13H), 5.745(s, 1H),
4.64−4.68 (d, J = 9.6 Hz, 1H), 4.20−4.24 (t, J = 6.3 Hz, 1H), 3.72−
3.74 (d, J = 6.3 Hz, 2H), 2.28 (s, 3H). 13C NMR (75 MHz, CD3OD):
δ = 184.8, 144.2, 143.8, 139.9, 139.6, 130.3, 129.8, 129.4, 129.1, 129.0,
128.7, 128.4, 127.9, 127.9, 127.2, 64.9, 64.0, 56.1, 52.8, 21.5. HRMS:
calcd for C30H32N4O2S2 [M]+ 544.1967, found 544.1957.
(S)-4-Nitro-1-phenyl-3-p-tolylbutan-1-one (13g).10c 42.5 mg, 75%
1
yield. [α]20 = −22.0 (c = 0.8 M, CHCl3). H NMR (300 MHz,
D
CDCl3): δ = 7.89−7.92 (d, J = 7.2 Hz, 2H), 7.53−7.58 (t, J = 8.1 Hz,
1H), 7.41−7.46 (t, J = 7.8 Hz 2H), 7.10−7.18 (dd, J = 8.4, 8.4 Hz,
4H), 4.76−4.83 (dd, J = 6.6, 6.6 Hz, 1H), 4.16−4.68 (dd, J = 7.8, 8.1
Hz, 1H), 4.13−4.22 (m, 1H), 3.34−3.50 (m, 2H), 2.30 (s, 1H). HPLC
(Chiralpak AD-H, 2-propanol/hexane = 15/85, flow rate 1.0 mL/min,
λ = 254 nm): tmajor = 11.0 min, tminor (not found).
General Procedure for 1a-Catalyzed Asymmetric Michael
Addition of Aromatic Ketones to Nitroolefins. The nitroolefin
(0.2 mmol), aromatic ketone (0.6 mmol), PhCO2H (0.03 mmol), and
catalyst 1a (0.03 mmol) were placed in a 1.5 mL vial equipped with a
Teflon-coated stir bar. DCM (0.2 mL) was added under air. The vial
was capped with a white polyethylene stopper, and the resulting
mixture was stirred at room temperature until the reaction was
complete (monitored by TLC). Then the mixture was purified by
column chromatography on silica gel (petroleum ether/ethyl acetate as
the eluents) to afford the desired product. The enantiomeric excess of
the pure product was determined by chiral HPLC analysis.
(S)-3-(4-Methoxyphenyl)-4-nitro-1-phenylbutan-1-one (13h).10d
1
43.0 mg, 72% yield. [α]20 = −22.7 (c = 1.0 M, CHCl3). H NMR
D
(300 MHz, CDCl3): δ = 7.90−7.92 (d, J = 8.4 Hz, 2H), 7.54−7.59 (t, J
= 6.9 Hz 1H), 7.42−7.47 (t, J = 7.2 Hz, 2H), 7.18−7.21 (d, J = 8.4 Hz,
2H), 6.83−6.86 (d, J = 8.4 Hz, 2H), 4.76−4.82 (dd, J = 6.9, 6.3 Hz,
1H), 4.60−4.67 (dd, J = 8.1, 8.1 Hz, 1H), 4.08−4.22 (m, 1H), 3.76 (s,
3H), 3.34−3.52 (m, 2H). HPLC (Chiralpak AD-H, 2-propanol/
hexane = 15/85, flow rate 1.0 mL/min, λ = 254 nm): tmajor = 16.7 min,
tminor (not found).
(S)-3-(4-Chlorophenyl)-4-nitro-1-phenylbutan-1-one (13i).10d
(S)-4-Nitro-1,3-diphenylbutan-1-one (13a).8 38.8 mg, 72% yield.
[α]20D = −26.2 (c = 1.0 M, CHCl3). 1H NMR (300 MHz, CDCl3): δ =
7.90−7.93 (d, J = 8.4 Hz, 2H), 7.55−7.59 (t, J = 7.2 Hz, 1H) 7.42−
7.47 (t, J = 7.5 Hz, 2H), 7.29−7.35 (m, 5H), 4.80−4.86 (dd, J = 6.6,
6.6 Hz, 1H), 4.65−4.72 (dd, J = 8.1, 8.1 Hz, 1H), 4.18−4.27 (m, 1H),
3.37−3.53 (m, 2H). HPLC (Chiralpak AD-H, 2-propanol/hexane =
10/90, flow rate 1.0 mL/min, λ = 254 nm): tmajor= 15.9 min, tminor (not
found).
1
43.0 mg, 71% yield. [α]20 = −24.7 (c = 0.9 M, CHCl3). H NMR
D
(300 MHz, CDCl3): δ = 7.89−7.92 (d, J = 8.4 Hz, 2H), 7.56−7.61 (t, J
= 7.2 Hz, 1H), 7.44−7.49 (t, J = 7.2 Hz, 2H), 7.21−7.32 (m, 4H),
4.78−4.85 (dd, J = 6.6, 6.6 Hz, 1H), 4.63−4.69 (dd, J = 8.1, 8.1 Hz,
1H), 4.17−4.26 (m, 1H), 3.35−3.50 (m, 2H). HPLC (Chiralpak AD-
H, 2-propanol/hexane =10/90, flow rate 1.0 mL/min, λ = 254 nm):
tmajor = 18.5 min, tminor (not found).
(S)-3-(4-Bromophenyl)-4-nitro-1-phenylbutan-1-one (13j).10d
(S)-4-Nitro-3-phenyl-1-p-tolylbutan-1-one (13b).8 42.5 mg, 75%
1
53.6 mg, 77% yield. [α]20 = −25.3 (c = 1.0 M, CHCl3). H NMR
D
1
yield. [α]20 = −34.0 (c = 0.6 M, CHCl3). H NMR (300 MHz,
D
(300 MHz, CDCl3): δ = 7.82−7.84 (d, J = 7.2 Hz, 1H), 7.34−7.53 (m,
5H), 7.08−7.11 (d, J = 8.4 Hz, 2H), 4.70−4.77 (dd, J = 6.3, 6.3 Hz,
1H), 4.55−4.62 (dd, J = 8.1, 8.4 Hz, 1H), 4.08−4.17 (m, 1H), 3,28−
3.42 (m, 2H). HPLC (Chiralpak AD-H, 2-propanol/hexane = 10/90,
flow rate 1.0 mL/min, λ = 254 nm): tmajor = 19.1 min, tminor = 28.4 min.
CDCl3): δ = 7.80−7.85 (d, J = 8.1 Hz, 2H), 6.99−7.59 (m, 7H), 4.80−
4.86 (dd, J = 6.6, 6.6 Hz, 1H), 4.64−4.71 (dd, J = 8.1, 8.1 Hz, 1H),
4.17−4.26 (m, 1H), 3.31−3.49 (m, 2H), 2.19 (s, 3H). HPLC
(Chiralpak AD-H, 2-propanol/hexane =10/90, flow rate 1.0 mL/min,
λ = 254 nm): tmajor = 18.6 min, tminor = 30.2 min.
(S)-3-(2-Bromophenyl)-4-nitro-1-phenylbutan-1-one (13k).10d
(S)-1-(4-Methoxyphenyl)-4-nitro-3-phenylbutan-1-one (13c).8
1
49.4 mg, 71% yield. [α]20 = −33.3 (c = 1.0 M, CHCl3). H NMR
D
1
43.7 mg, 73% yield. [α]20 = −27.7 (c = 0.6 M, CHCl3). H NMR
D
(300 MHz, CDCl3): δ = 7.93−7.96 (d, J = 7.2 Hz, 2H), 7.26−7.62 (m,
4H), 7.11−7.29 (m, 3H), 4.85−4.87 (d, J = 6.6 Hz, 2H), 4.65−4.74
(m, 1H), 3.47−3.62 (m, 2H). HPLC (Chiralpak AD-H, 2-propanol/
hexane = 10/90, flow rate 1.0 mL/min, λ = 254 nm): tmajor = 15.8 min,
tminor = 19.1 min.
(300 MHz, CDCl3): δ = 7.88−7.91 (d, J = 7.2 Hz, 2H), 7.23−7.35 (m,
5H), 6.90−6.92 (d, J = 6.9 Hz, 2H), 4.80−4.87 (dd, J = 6.6, 6.3 Hz,
1H), 4.64−4.71 (dd, J = 8.1, 8.1 Hz, 1H), 4.10−4.25 (m, 2H), 3.86 (s,
3H), 3.31−3.46 (m, 2H). HPLC (Chiralpak AD-H, 2-propanol/
hexane = 15/85, flow rate 1.0 mL/min, λ = 254 nm): tmajor = 23.4 min,
tminor = 37.3 min.
(S)-4-Nitro-1-phenyl-3-(4-(trifluoromethyl)phenyl)butan-1-one
(13l). Amorphous solid, 54.0 mg, 80% yield. [α]20 = −22.2 (c = 0.3
D
1
(S)-4-Nitro-1-(4-nitrophenyl)-3-phenylbutan-1-one (13d). Amor-
phous solid, 51 mg, 81% yield. [α]20D = −27.3 (c = 1.0 M, CHCl3). 1H
NMR (300 MHz, CDCl3): δ = 8.26−8.29 (d, J = 8.7 Hz, 2H), 8.04−
8.07 (d, J = 8.4 Hz, 2H), 7.27−7.36 (m, 5H), 4.78−4.85 (dd, J = 7.2,
6.9 Hz, 1H), 4.67−4.74 (dd, J = 7.2, 7.2 Hz, 1H), 4.18−4.27 (m, 1H),
3.51−5.53 (m, 2H). 13C NMR (75 Hz, CDCl3): δ = 195.5, 150.5,
140.7, 138.6, 129.2, 129.1, 128.1, 127.4, 124.0, 79.4, 42.1, 39.2. HPLC
(Chiralpak AD-H, 2-propanol/hexane = 20/80, flow rate 1.0 mL/min,
λ = 254 nm): tmajor = 43.1 min, tminor (not found). HRMS: calcd for
C16H14N2O5 [M + Na]+ 337.0800, found 337.0798.
M, CHCl3). H NMR (300 MHz, CDCl3): δ = 7.83−7.85 (d, J = 7.2
Hz, 2H), 7.47−7.51 (t, J = 7.2 Hz, 3H), 7.34−7.41 (m, 4H), 4.75−
4.82 (dd, J = 6.3, 6.3 Hz, 1H), 4.60−4.67 (dd, J = 8.4, 8.1 Hz, 1H),
4.19−4.29 (m, 1H), 3.32−3.47 (m, 2H). 13C NMR (75 Hz, CDCl3): δ
= 196.3, 143.2, 136.2, 133.8, 130.4, 130.0, 128.8, 128.0, 126.1, 125.7,
79.1, 41.2, 39.01. HPLC (Chiralpak AD-H, 2-propanol/hexane =10/
90, flow rate 0.9 mL/min, λ = 254 nm): tmajor = 14.9 min, tminor = 23.3
min. HRMS: calcd for C17H14F3NO3 [M + Na]+ 360.0823, found
360.0828.
(S)-4-Nitro-1-phenyl-3-(3-(trifluoromethyl)phenyl)butan-1-one
(S)-4-Nitro-3-phenyl-1-(4-(trifluoromethyl)phenyl)butan-1-one
(13m). Amorphous solid, 53.3 mg, 79% yield. [α]20D = −27.8 (c = 1.0
(13e). Amorphous solid, 58.7 mg, 87% yield. [α]20 = −24.8 (c = 1.0
1
M, CHCl3). H NMR (300 MHz, CDCl3): δ = 7.90−7.93 (d, J = 8.1
D
1
M, CHCl3). H NMR (300 MHz, CDCl3): δ = 7.99−8.02 (d, J = 8.1
Hz, 2H), 7.43−7.61 (m, 7H), 4.83−4.89 (dd, J = 6.3, 6.3 Hz, 1H),
4.47−4.67 (dd, J = 8.1, 8.1 Hz, 1H), 4.26−4.36 (m, 1H), 3.46−3.48
(d, J = 6.9 Hz, 2H). 13C NMR (75 Hz, CDCl3): δ = 196.3, 140.3,
136.2, 133.8, 131.6, 131.2, 129.6, 128.8, 128.0, 125.7, 124.9, 124.3,
79.1, 41.3, 39.0. HPLC (Chiralpak AD-H, 2-propanol/hexane = 10/90,
flow rate 0.9 mL/min, λ = 254 nm): tmajor = 12.2 min, tminor = 13.8 min.
HRMS: calcd for C17H14F3NO3 [M + Na]+ 360.0823, found 360.0828.
(S)-4-Nitro-1-phenyl-3-(2-(trifluoromethyl)phenyl)butan-1-one
(13n). Colorless liquid, 56.0 mg, 83% yield. [α]20D = −26.5 (c = 0.8 M,
CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.90−7.93 (d, J = 6.9 Hz,
Hz, 2H), 7.70−7.73 (d, J = 8.1 Hz, 2H), 7.26−7.43 (m, 5H), 4.78−
4.85 (dd, J = 6.9, 7.2 Hz, 1H), 4.67−4.73 (dd, J = 7.5, 7.2 Hz, 1H),
4.18−4.27 (m, 1H), 3.43−3.56 (m, 2H). 13C NMR (75 Hz, CDCl3): δ
= 196.0, 139.1, 138.8, 135.0, 134.6, 129.2, 128.4, 128.0, 127.4, 125.8,
79.4, 41.8, 39.2. HPLC (Chiralpak AD-H, 2-propanol/hexane =15/85,
flow rate 1.0 mL/min, λ = 254 nm): tmajor = 14.8 min, tminor = 18.4 min.
HRMS: calcd for C17H14F3NO3[M + Na]+ 360.0823, found 360.0828.
(S)-1-(4-Bromophenyl)-4-nitro-3-phenylbutan-1-one (13f). Amor-
phous solid, 55.7 mg, 80% yield. [α]20 = −32.6 (c = 1.0 M, CHCl3).
D
4108
dx.doi.org/10.1021/jo300011x | J. Org. Chem. 2012, 77, 4103−4110

The Journal of Organic Chemistry
Note
2H), 7.69−7.72 (d, J = 7.8 Hz, 1H), 7.36−7.60 (m, 6H), 4.77−4.91
(m, 2H), 4.63−4.69 (dd, J = 6.6, 6.9 Hz, 1H), 3.40−3.58 (m, 2H). 13C
NMR (75 Hz, CDCl3): δ = 196.4, 138.0, 136.2, 133.7, 132.5, 128.8,
128.0, 127.9, 127.6, 126.9, 126.0, 122.4, 78.4, 41.6, 34.7. HPLC
(Chiralpak AD-H, 2-propanol/hexane = 10/90, flow rate 0.9 mL/min,
λ = 254 nm): tmajor = 12.1 min, tminor = 14.6 min. HRMS: calcd for
C17H14F3NO3 [M + Na]+ 360.0823, found 360.0828.
(300 MHz, CDCl3): δ = 7.45−7.56 (m, 4H), 4.70−4.77 (dd, J = 6.6,
6.6 Hz, 1H), 4.59−4.66 (dd, J = 8.1, 8.1 Hz, 1H), 4.05−4.14 (m, 1H),
2.94−2.96 (d, J = 6.9 Hz, 2H), 2.14 (s, 3H). 13C NMR (75 Hz,
CDCl3): δ = 204.7, 140.1, 131.6, 131.1, 129.6, 125.6, 124.8, 124.1,
78.9, 45.8, 38.7, 30.3. HPLC (Chiralpak AS-H, 2-propanol/hexane
=15/85, flow rate 0.9 mL/min, λ = 210 nm): tmajor = 14.8 min, tminor
=
26.9 min.
(R)-4-(Furan-2-yl)-5-nitropentan-2-one (14h).9f 37.9 mg, 96%
(R)-3-(Furan-2-yl)-4-nitro-1-phenylbutan-1-one (13o).10d 36.8
yield. [α]20 = +6.2 (c = 1.0 M, CHCl3). 1H NMR (300 MHz,
1
mg, 71% yield. [α]20 = −20.2 (c = 1.0 M, CHCl3). H NMR (300
D
D
CDCl3): δ = 7.34 (s, 1H), 6.29−6.30 (d, J = 3.3 Hz, 1H), 6.14−6.15
(d, J = 3.3 Hz, 1H), 4.62−4.73 (m, 2H), 4.06−4.14 (m, 1H), 2.85−
3.02 (m, 2H), 2.17 (s, 3H). HPLC (Chiralpak AD-H, 2-propanol/
hexane = 10/90, flow rate 0.9 mL/min, λ = 254 nm): tmajor = 12.4 min,
tminor = 14.2 min.
MHz, CDCl3): δ = 7.94−7.96 (d, J = 8.4 Hz, 2H), 7.56−7.93 (m, 1H),
7.45−7.50 (m, 2H), 7.33−7.34 (m, 1H), 6.28−6.230 (d, J = 4.8 Hz,
1H), 6.18−6.19 (d, J = 5.1 Hz, 1H), 4.71−4.84 (m, 2H), 4.29−4.38
(m, 1H), 3.27−3.57 (m, 2H). HPLC (Chiralpak AD-H, 2-propanol/
hexane =10/90, flow rate 1.0 mL/min, λ = 254 nm): tmajor = 14.4 min,
tminor = 17.5 min.
General Procedure for 1a-Catalyzed Asymmetric Michael
Addition of Acetone to Nitroolefins. The nitroolefin (0.2 mmol),
PhCO2H (0.03 mmol), and catalyst 1a (0.03 mmol) were placed in a
1.5 mL vial equipped with a Teflon-coated stir bar. Acetone (2 mmol)
was added followed by CHCl3 (0.2 mL) under air. The vial was capped
with a white polyethylene stopper and the resulting mixture was stirred
at room temperature until the reaction was complete (monitored by
TLC). Then the mixture was purified by column chromatography on
silica gel (petroleum ether/ethyl acetate as the eluents) to afford the
desired product. The enantiomeric excess of the pure product was
determined by chiral HPLC analysis.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H NMR spectra of the compounds 1a−f, 13a−o, 14a−h and
13C NMR spectra of the compounds 1a−f, 13d−f, and 13l−n.
This material is available free of charge via the Internet at
http://pubs.acs.org/.
AUTHOR INFORMATION
■
Corresponding Author
(S)-5-Nitro-4-phenylpentan-2-one (14a)7. 38.1 mg, 92% yield.
[α]20D = +3.6 (c = 0.8 M, CHCl3). 1H NMR (300 MHz, CDCl3): δ =
7.20−7.35 (m, 5H), 4.66−4.72 (dd, J = 6.9, 6.9 Hz, 1H), 4.56−4.62
(dd, J = 7.8, 7.8 Hz, 1H), 3.95−4.05 (m, 1H), 2.90−2.92 (d, J = 7.2
Hz, 2H), 2.11 (s, 3H). HPLC (Chiralpak AD-H, 2-propanol/hexane =
*Tel: (+86)871-5031119. Fax: (+86)871-5035538. E-mail: (Z.-
H.S.) zhihui_shao@hotmail.com, (F.-Z.P.) pengfangzhi@ynu.
edu.cn.
Notes
10/90, flow rate 0.9 mL/min, λ = 254 nm): tmajor = 12.8 min, tminor
=
The authors declare no competing financial interest.
13.8 min.
(S)-5-Nitro-4-p-tolylpentan-2-one (14b)7. 39.8 mg, 90% yield.
[α]20D = −1.7 (c = 1.0 M, CHCl3). 1H NMR (300 MHz, CDCl3): δ =
7.08−7.14 (dd, J = 8.1, 8.1 Hz, 4H), 4.63−4.69 (dd, J = 6.9 Hz, 1H),
4.53−4.59 (dd, J = 7.8 Hz, 1H), 3.91−4.00 (m, 1H), 2.87−2.90 (d, J =
6.6 Hz, 2H), 2.31 (s, 3H), 2.11 (s, 3H). HPLC (Chiralpak AD-H, 2-
ACKNOWLEDGMENTS
■
We gratefully acknowledge financial support from the NSFC
(20962023, 21162034), the Program for New Century
Excellent Talents in University (NCET-10-0907), and the
Education Department of Yunnan Province (2010Y241).
propanol/hexane = 10/90, flow rate 0.9 mL/min, λ = 254 nm): tmajor
11.5 min, tminor = 12.8 min.
=
(S)-4-(4-Methoxyphenyl)-5-nitropentan-2-one (14c)7. 43.2 mg,
REFERENCES
1
91% yield. [α]20 = −1.3 (c = 1.1 M, CHCl3). H NMR (300 MHz,
■
D
(1) For a recent review on organocatalysis, see: Bertelsen, S.;
Jørgensen, K. A. Chem. Soc. Rev. 2009, 38, 2178.
CDCl3): δ = 7.11−7.14 (d, J = 8.7 Hz, 2H), 6.83−6.86 (d, J = 8.7 Hz,
2H), 4.62−4.69 (dd, J = 6.9, 6.9 Hz, 1H), 4.51−4.58 (dd, J = 7.8, 7.8
Hz, 1H), 3.90−4.01 (m, 1H), 3.77 (s, 3H), 2.86−2.89 (d, J = 7.2 Hz,
2H), 2.10 (s, 3H). HPLC (Chiralpak AD-H, 2-propanol/hexane = 10/
90, flow rate 0.9 mL/min, λ = 254 nm): tmajor = 17.4 min, tminor = 19.3
min.
(2) For recent reviews on catalytic asymmetric Michael addition of
nitroolefins, see: (a) Sulzer-Moss, S.; Alexakis, A. Chem. Commun.
2007, 3123. (b) Roca-Lopez, D.; Sadaba, D.; Delso, I.; Herrera, R. P.;
Tejero, T.; Merino, P. Tetrahedron: Asymmetry 2010, 21, 2561.
(3) For selected examples, see: (a) Okino, T.; Hoashi, Y.; Takemoto,
Y. J. Am. Chem. Soc. 2003, 125, 12672. (b) McCooey, S. H.; Connon,
S. J. Angew. Chem., Int. Ed. 2005, 44, 6367. (c) Li, H.; Wang, Y.; Tang,
L.; Wu, F.; Liu, X.; Guo, C.; Foxman, B. M.; Deng, L. Angew. Chem.,
Int. Ed. 2005, 44, 105.
(4) For selected examples, see: (a) Betancort, J. M.; Barbas, C. F. III.
Org. Lett. 2001, 3, 3737. (b) Mase, N.; Thayumanavan, R.; Tanaka, F.;
Barbas, C. F. III. Org. Lett. 2004, 6, 2527. (c) Wang, W.; Wang, J.; Li,
H. Angew. Chem., Int. Ed. 2005, 44, 1369. (d) Zhu, S.; Yu, S; Ma, D.
Angew. Chem., Int. Ed. 2008, 47, 545.
(5) For selected examples, see: (a) List, B.; Pojarliev, P.; Martin, H. J.
Org. Lett. 2001, 3, 2423. (b) Wang, W.; Wang, J.; Li, H. Angew. Chem.,
Int. Ed. 2005, 44, 1369. (c) Luo, S.; Mi, X.; Zhang, L.; Liu, S.; Xu, H.;
Cheng, J. Angew. Chem., Int. Ed. 2006, 45, 3093. (d) Chen, J.; Fu, L.;
Zou, Y.; Chang, N.; Rong, J.; Xiao, W. Org. Biomol. Chem. 2011, 9,
5280.
(S)-4-(4-Bromophenyl)-5-nitropentan-2-one (14d).9f 53.8 mg,
1
94% yield. [α]20 = +2.3 (c = 1.0 M, CHCl3). H NMR (300 MHz,
D
CDCl3): δ = 7.44−7.46 (d, J = 8.1 Hz, 2H), 7.09−7.12 (d, J = 8.4 Hz,
2H), 4.64−4.71 (dd, J = 6.6, 6.6 Hz, 1H), 4.53−4.60 (dd, J = 7.8, 8.1
Hz, 1H), 2.87−2.90 (d, J = 6.9 Hz, 2H), 2.12 (s, 3H). HPLC
(Chiralpak AD-H, 2-propanol/hexane = 10/90, flow rate 0.9 mL/min,
λ = 254 nm): tmajor = 16.4 min, tminor = 18.9 min.
(S)-4-(4-Chlorophenyl)-5-nitropentan-2-one (14e).9f 46.1 mg, 93%
yield. [α]20 = +2.5 (c = 1.0 M, CHCl3). 1H NMR (300 MHz,
D
CDCl3): δ = 7.29−7.31 (d, J = 8.4 Hz, 2H), 7.15−7.17 (d, J = 8.4 Hz,
2H), 4.65−4.71 (dd, J = 6.6, 6.6 Hz, 1H), 4.53−4.60 (dd, J = 8.1, 7.8
Hz, 1H), 2.88−2.90 (d, J = 7.2 Hz, 2H), 2.12 (s, 3H). HPLC
(Chiralpak AD-H, 2-propanol/hexane = 10/90, flow rate 0.9 mL/min,
λ = 254 nm): tmajor = 15.0 min, tminor = 17.1 min.
(S)-4-(2-Bromophenyl)-5-nitropentan-2-one (14f).9f 52.6 mg, 92%
yield. [α]20 = +16.4 (c = 1.0 M, CHCl3). 1H NMR (300 MHz,
D
(6) (a) Tsogoeva, S. B.; Wei, S. Chem. Commun. 2006, 1451.
(b) Yalalov, D. A.; Tsogoeva, S. B.; Schmatz, S. Adv. Synth. Catal.
2006, 348, 826.
(7) Huang, H.; Jacobsen, E. N. J. Am. Chem. Soc. 2006, 128, 7170.
(8) Liu, K.; Cui, H.; Nie, J.; Dong, K.; Li, X.; Ma, J. Org. Lett. 2007, 9,
923.
CDCl3): δ = 7.58−7.61 (d, J = 7.8 Hz, 1H), 7.12−7.31 (m, 3H), 4.69−
4.80 (d, J = 6.6 Hz, 2H), 4.42−4.51 (m, 1H), 2.91−3.08 (m, 2H), 2.16
(s, 3H). HPLC (Chiralpak AS-H, 2-propanol/hexane = 15/85, flow
rate 0.9 mL/min, λ = 254 nm): tmajor = 16.3 min, tminor = 20.1 min.
(S)-5-Nitro-4-(3-(trifluoromethyl)phenyl)pentan-2-one (14g).9g
1
50.1 mg, 91% yield. [α]20 = +2.0 (c = 1.0 M, CHCl3). H NMR
D
4109
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The Journal of Organic Chemistry
Note
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(11) To our knowledge, there is only one report (ref 10c) concerning
catalytic asymmetric addition of both aromatic ketones and acetone to
various nitroolefins (four nitroolefins); however, only one aromatic
ketone (acetophenone) was examined. Moreover, for β-4-MeOC6H4-
substituted nitroolefin, the reaction yield was moderate (43%). Wang’s
report (ref 9c) describes catalytic asymmetric addition of acetone to a
variety of nitroolefins and catalytic asymmetric addition of two
aromatic ketones to one nitroolefin (β-nitrostyrene); however, for the
addition products of acetone, the enantioselectivities are generally
below 90% ee; for the addition products of two aromatic ketones, the
enantioselectivities are below 90% ee and the yields are moderate
(46% and 33%).
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4110
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