Enantioselective conjugate addition of 1-bromonitroalkanes to α,β-unsaturated aldehydes catalyzed by chiral secondary amines

Article abstract of DOI:10.1016/j.tetasy.2009.01.003

Highly enantioselective conjugate addition of bromonitromethane to α,β-unsaturated aldehydes catalyzed by chiral secondary amines has been achieved. Diphenylprolinol triethylsilyl ether was found to be the best catalyst for the reaction under MeOH/AcONa s

Full text of DOI:10.1016/j.tetasy.2009.01.003

Tetrahedron: Asymmetry 20 (2009) 355–361
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantioselective conjugate addition of 1-bromonitroalkanes to
a,b-unsaturated aldehydes catalyzed by chiral secondary amines
*
Jun-min Zhang, Zhi-peng Hu, Li-ting Dong, Yi-ning Xuan, Chun-Liang Lou, Ming Yan
The Industrial Institute of Fine Chemicals and Synthetic Drugs, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Highly enantioselective conjugate addition of bromonitromethane to
a,b-unsaturated aldehydes cata-
Received 9 December 2008
Accepted 13 January 2009
Available online 18 March 2009
lyzed by chiral secondary amines has been achieved. Diphenylprolinol triethylsilyl ether was found to
be the best catalyst for the reaction under MeOH/AcONa system. Various b-aryl acroleins afforded nitro-
cyclopropanes with excellent enantioselectivities and in good yields; however, the reaction of b-alkyl
acroleins did not provide the corresponding nitrocyclopropanes. Substituted 1-bromonitromethanes,
such as 1-bromonitroethane and 1-phenyl-1-bromonitromethane, were also applied in the reaction with
excellent enantioselectivities and improved diastereoselectivities. The new methodology is efficient for
preparing highly substituted chiral nitrocyclopropanes.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
vation of
ering mechanism.10 Thus, the conjugate addition of 1-halogenated
nitroalkanes to ,b-unsaturated aldehydes and ketones in the pres-
ence of chiral amine catalysts is also a promising method for asym-
metric synthesis of nitrocyclopropanes. Ley et al. reported the first
a,b-unsaturated aldehydes and ketones, via a LUMO low-
Chiral cyclopropane motifs are widely found in a great number
of drugs and natural products.1 These compounds exhibit various
useful biological activities, such as enzyme inhibition, insecticidal,
antifungal, herbicidal, antimicrobial, antitumor, and antiviral activ-
ities.2 Synthetic methods of chiral cyclopropanes have been exten-
sively studied.3 Among them, the asymmetric conjugate addition
and consequent intramolecular alkylation is extremely powerful
for the synthesis of chiral cyclopropanes (Scheme 1). Various Mi-
chael acceptor and nucleophilic agents with a leaving group could
be applied in this transformation.4
a
organocatalytic nitrocyclopropanation of
a,b-unsaturated ketones
with bromonitromethane using the proline tetrazole catalyst.11
Córdova et al. explored the reaction of a,b-unsaturated aldehydes
with bromonitromethane catalyzed by chiral secondary amines.12
Recently, we studied the conjugate addition of 1-bromonitroalk-
anes to a,b-unsaturated aldehydes catalyzed by several achiral sec-
ondary amines.13 We found that the CHCl3/Et3N system used by
Córdova et al. resulted in complicated mixtures of products, from
which only low yield of nitrocyclopropanes was obtained, and
instead the MeOH/AcONa system provided nitrocyclopropanes in
much better yields. In addition, we also found that the substituted
1-bromonitromethanes could improve the diastereoselectivities of
the reaction efficiently. Encouraged by the results, we explored the
Nitrocyclopropanes are
a special class of cyclopropane
compounds, which are presented in some natural products such
as the peptidolactone hormaomycin5 and the broad spectrum anti-
biotic Trovafloxacin.6 Furthermore, nitrocyclopropanes can be con-
verted into a wide range of useful compounds.7 Asymmetric
synthesis of nitrocyclopropanes has been developed based on the
reaction of nitroalkyl carbene with alkenes,8 conjugate addition
asymmetric nitrocyclopropanation of
a,b-unsaturated aldehydes
of
a
-halogenated nucleophiles to nitroolefins.9 In recent years,
with 1-bromonitroalkanes using chiral secondary amines as the
catalysts. Herein, our new experimental results are reported in
detail.
chiral secondary amines, for example, proline and its derivatives,
imidazolidinones, have been found to be efficient catalysts for acti-
Y
Y
*
X
H 2
C
cat*
GL
X
+
Y
LG
R
*
*
R
X
R
Scheme 1. Asymmetric conjugate addition and consequent intramolecular alkylation.
* Corresponding author. Tel./fax: +86 20 39943049.
E-mail address: yanming@mail.sysu.edu.cn (M. Yan).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.01.003

356
J.-m. Zhang et al. / Tetrahedron: Asymmetry 20 (2009) 355–361
Table 2
2. Results and discussions
Solvent screening for the reaction of 7a and 8aa
NO2
NO2
5 (10 mol%)
A variety of chiral secondary amines were studied in the reaction
(Scheme 2). Initially, the reaction of cinnamaldehyde 7a and bro-
monitromethane 8a was examined in CHCl3/Et3N catalyzed by
diphenylprolinol TMS ether 5 (the reaction conditions used by
Córdova et al.).12 The reaction afforded complicated mixtures of
products, and nitrocyclopropanes 9a/9a0 were obtained in only
36% GC yield and with 85% ee (Table 1, entry 5). Thus, improved reac-
tion conditions were explored based on our previous study.13 The
reaction was re-examined in methanol with a number of acid and
base additives. The results are summarized in Table 1. The reaction
did not occur in the absence of additives, and benzoic acid was an
inefficient additive (Table 1, entries 1–2). NaI provided the nitrocy-
clopropanes 9a/9a0 with good enantioselectivities, however in low
yield. Et3N provided a slightly better yield, but the enantioselectivi-
ties were lower. AcONa was identified as the best additive consider-
ing the improved yield and enantioselectivities. In addition, the
reactionwasfasterthanthatwithother additives. Thecompletecon-
sumption of cinnamaldehyde was achieved after 3 h as indicated by
the TLC analysis. The results undoubtedly demonstrated the superi-
ority of MeOH/AcONa system.
CHO
AcONa (100 mol%)
+
+
Br
NO2
Solvent, r.t., 3h
Ph
CHO
Ph
Ph
CHO
7a
8a
9a
9a'
c
Entry
Solvent
Yieldb (%)
9a:9a0
eed (%) (9a/9a0)
1
2
3
4
5
6
7
MeOH
EtOH
76
66
62
59
46
58
56
60:40 (67:33)e
47:53 (67:33)
50:50 (63:37)
44:56 (50:50)
57:43 (58:42)
52:48 (60:40)
50:50 (62:38)
89/87
84/89
90/85
83/87
60/60
82/86
85/87
i-PrOH
THF
MeCN
CH2Cl2
CHCl3
a
The reactions were carried out at room temperature for 3 h with cinnamalde-
hyde 7a (0.25 mmol), bromonitromethane 8a (0.26 mmol), 5 (0.025 mmol), AcONa
(0.26 mmol), and 1.0 ml solvent.
b
GC yield of combined 9a and 9a0.
The ratios of 9a/9a0 were determined by GC analysis.
c
d
e
The ee values of 9a and 9a0 were determined by chiral GC.
The values in parentheses were determined by GC after leaving the reaction
mixtures for 24 h.
(Table 2, entries 1–7). The result suggests that 9a is thermodynami-
cally favorable product and that 9a0 is kinetically favorable product.
After setting up of the optimized reaction system, chiral second-
ary amines 1–6 were further examined in order to improve the
enantioselectivity of the reaction, and the results are summarized
in Table 3. MacMillan0s catalysts 1–2 were inefficient for the
transformation, and only trace of 9a/9a0 were obtained after 3 h.
The optimization of reaction solvent was studied with AcONa as
the additive and the results are listed in Table 2. EtOH, i-PrOH, THF,
CH2Cl2, and CHCl3 could also be used in the reaction, but lower yields
wereobtainedincomparisonwithMeOH(Table2, entries2–4, 6, and
7 vs entry 1). CH3CN provided nitrocyclopropanes in low yields and
enantioselectivities. It is noted that the ratio of 9a/9a0 increased gen-
erally with the extension of the standby time of reaction mixtures
Proline
3 provided moderate yield of the product, but the
enantioselectivity was negligible. Diphenylprolinol 4 provided
good enantioselectivity, however, in lower yield. The sterically
demanding diphenylprolinol triethylsilyl ether 6 provided better
yield and enantioselectivity than diphenylprolinol TMS ether 5.
Another advantage of 6 is the much better chemical stability than
5. The color change and decomposition of 5 were observed during
the storage; however 6 was highly stable even after the long-term
storage. The effect of the reaction temperature on the reaction was
also studied. The enantioselectivity was improved with the
decrease of the reaction temperature. 96% Ee was achieved under
0 °C; however, the decrease of temperature to ꢀ20 °C did not im-
prove the enantioselectivity furthermore (Table 3, entries 7–8).
The chemical yields of 9a/9a0 were almost consistent under the dif-
ferent reaction temperatures (Table 3, entries 6–8).
CH3
CH3
O
O
N
N
COOH
Ph
N
H
N
N
Ph
Ph
H
H
1
2
3
Ph
Ph
Ph
Ph
OTMS
N
Ph
N
H
N
H
H
OH
OTES
4
5
6
Scheme 2. Chiral secondary amine catalysts.
Table 3
Catalyst screening for the reaction of 7a and 8aa
Table 1
Additive screening for the reaction of 7a and 8a catalyzed by 5a
NO2
NO2
Catalyst (10 mol%)
AcONa (100 mol%)
CHO
NO2
+
+
NO2
Br
NO2
5 (10 mol%)
MeOH, r.t., 3 h
CHO
Ph
CHO
Ph
Ph
CHO
Additive (100 mol%)
+
+
Br
NO2
7a
8a
9a
9a'
MeOH, r.t.
Ph
CHO
Ph
Ph
CHO
7a
8a
9a
9a'
c
Entry
Catalyst
Yieldb (%)
9a:9a0
eed (%) (9a/9a0)
c
Entry
Additive
Time (h)
Yieldb (%)
9a:9a0
eed (%) (9a/9a0)
1
2
3
4
1
2
3
4
5
6
6
6
7
6
23:77
23:77
47:53
57:43
60:40
55:45
44:56
33:67
48/32
11/14
5/10
80/70
89/87
90/94
96/96
96/94
1
2
3
4
5f
6
—
24
24
24
24
12
3
Trace
Trace
14
NDe
ND
70:30
57:43
62:38
60:40
ND
ND
61
48
76
79
79
81
PhCOOH
NaI
83/78
66/65
85/85
89/87
5
Et3N
Et3N
AcONa
28
6
36
7e
8f
76 (65g)
a
Cinnamaldehyde 7a (0.25 mmol), bromonitromethane 8a (0.26 mmol),
5
5
a
The reactions were carried out at room temperature for 3 h with cinnamalde-
hyde 7a (0.25 mmol), bromonitromethane 8a (0.26 mmol), catalyst (0.025 mmol),
AcONa (0.26 mmol), and 1.0 ml methanol.
(0.025 mmol), additive (0.26 mmol), and 1.0 ml methanol were used.
b
GC yield of combined 9a and 9a0.
c
The ratios of 9a/9a0 were determined by GC analysis.
b
GC yield of combined 9a and 9a0.
d
The ee values of 9a and 9a0 were determined by chiral GC.
c
The ratios of 9a/9a0 were determined by GC analysis.
The ee values of 9a and 9a0 were determined by chiral GC.
e
Not determined.
d
f
Cinnamaldehyde 7a (0.25 mmol), bromonitromethane 8a (0.26 mmol),
e
The reaction was carried out at 0 °C for 8 h.
The reaction was carried out at ꢀ20 °C for 22 h.
(0.025 mmol), Et3N (0.26 mmol), and 1.0 ml CHCl3 were used in this case.
f
g
Isolated yield of combined 9a and 9a0.

J.-m. Zhang et al. / Tetrahedron: Asymmetry 20 (2009) 355–361
357
Table 4
Reaction of a
, b -unsaturated aldehydes 7 with bromonitromethane 8a catalyzed by 6a
NO2
NO2
6
(10 mol%)
CHO
AcONa (100 mol%)
+
+
Br
NO2
MeOH, 0°C
R
CHO
R
R
CHO
7
8a
9
9'
Entry
7
Time (h)
Product (9/90)b
Yieldc (%)
eed (%) (9/90)
1
2
3
4
5
6
7
8
9
10
R = Ph 7a
8
9
8
8
16
8
8
8
19
24
9a/9a0 (55/45)
9b/9b0 (50/50)
9c/9c0 (66/34)
9d/9d0 (63/37)
9e/9e0 (68/32)
9f/9f0 (65/35)
9g/9g0 (67/33)
9h/9h0 (71/29)
9i/9i0 (67/33)
9j/9j0 (67/33)
68
63
63
67
61
65
68
61
48
46
96/96
98/92
91/95
94/94
89/96
96/96
88/96
95/89
89/92
88/86e
R = 4-NO2C6H4 7b
R = 4-ClC6H4 7c
R = 4-CH3C6H4 7d
R = 4-OMeC6H4 7e
R = 3-ClC6H4 7f
R = 2-ClC6H4 7g
R = 2-OMeC6H4 7h
R = 2-Furyl 7i
R = 3-Pyridyl 7j
a
a
,b-Unsaturated aldehyde 7 (0.25 mmol), bromonitromethane 8a (0.26 mmol), AcONa (0.26 mmol), 6 (0.025 mmol), and 1.0 ml methanol were used in the reaction.
b
c
The ratios of 9/90 were determined by GC analysis.
Isolated yield of combined 9 and 90.
The ee values of 9 and 90 were determined by chiral GC or HPLC.
The ee value of 9j0 was determined by chiral GC analysis of the corresponding alcohol obtained by NaBH4 reduction.
d
e
A variety of
a
,b-unsaturated aldehydes were investigated in the
(Table 5, entry 2). The ratio of 9k/9k0 was decreased to 14/86.
1-Bromonitropropane 8c gave low yield of product (Table 5, entry
3). 1-Bromo-1-phenylnitromethane 8d provided exclusively 9m0
with 99% ee and in good yield (Table 5, entry 4). The reaction of
ethyl 2-bromonitroacetate 8e afforded a complicated reaction
mixture, from which no nitrocyclopropane was isolated.
The observed enantioselectivities and diastereoselectivities of
the reactions can be rationalized based on a simple working model
(Scheme 3). The iminium cation I is generated from cinnamalde-
hyde and 6. The re face of double bond is efficiently shielded by
bulk diphenylmethyl group of 6. The bromonitroalkane anion
attacks I from the si face to provide II. The consequent intramolec-
ular alkylation of II provides the nitrocyclopropane product 90. The
epimerization of 90 under the reaction conditions affords 9. While a
substituent exists in the 1-bromonitromethane (R0 – H), the epi-
merization of 90 is inhibited, and the reaction provides 90 as the
major product.
reaction with bromonitromethane, and the results are summarized
in Table 4. Introduction of electron-withdrawing or electron-donat-
ing substituents on the phenyl ring of cinnamaldehyde did not exert
significant influence on the yield of nitrocyclopropanes (Table 4,
entries 2–8); however, the enantioselectivities increased as the sub-
stituent became more electron deficient (Table 4, entries 1–4). Alde-
hyde 7b, which has a 4-nitro group on the phenyl ring, provided the
best enantioselectivity. On the other hand, the ratio of 9/90 decreased
with theintroductionof moreelectron-deficientsubstituent. 3-Cl, 2-
Cl, and 2-MeO substituted cinnamaldehydes also afforded excellent
enantioselectivities and good yields. b-Heteroaryl- a,b-unsaturated
aldehydes, such as trans-3-(furan-2-yl)acrolein, and trans-3-
(pyridin-3-yl)acrolein were also applicable in the reaction. The
corresponding nitrocyclopropanes were obtained with good
enantioselectivities, however in lower yields (Table 4, entries
9–10). Acrolein and crotonaldehyde were examined in the reaction;
however, no nitrocyclopropane products could be obtained.
A single crystal was obtained from a solution of 9b/9b0 in EtOAc/
petroleum ether (V/V = 1/10).14 X-ray diffraction analysis uncov-
ered that the crystal was formed from the 9b0 (Fig. 1). The absolute
configuration was determined as (1S,2R,3S). Analogically the com-
pound 9b was proposed to have (1S,2S,3S) absolute configuration.
The result is consistent with the conclusion obtained via chemical
transformations by Córdova and co-workers.12
In our previous study, substituted bromonitromethanes were
found to provide better diastereoselectivities,13 and thus 1-bro-
monitroalkanes 8b–8e were examined in the reaction with cinna-
maldehyde 7a. The results are summarized in Table 5.
1-Bromonitroethane 8b provided the corresponding nitrocyclo-
propanes in moderate yield and with excellent enantioselectivities
3. Conclusion
In conclusion, the asymmetric conjugate addition of bromoni-
tromethane to
a,b-unsaturated aldehydes has been developed.
Diphenylprolinol triethylsilyl ether was identified as the best
catalyst for the reaction. Excellent enantioselectivities and good
yields were achieved for a number of b-aryl acroleins under
MeOH/AcONa system. Substituted 1-bromonitromethanes, such
as 1-bromonitroethane and 1-phenyl-1-bromonitromethane, also
provided excellent enantioselectivities and improved diastereose-
lectivities. The reaction is efficient for preparing highly substituted
chiral nitrocyclopropanes.
CHO
(R)
1
(S) 2
3
NO2
(S)
O2N
Figure 1. X-ray structure of the nitrocyclopropane 9b0.

358
J.-m. Zhang et al. / Tetrahedron: Asymmetry 20 (2009) 355–361
Table 5
Reaction of 1-bromonitroalkanes 8 with cinnamaldehyde 7a catalyzed by 6a
O2N
6 (10 mol%)
AcONa (100 mol%)
R'
O2N
R'
R'
CHO
+
+
Br
NO2
MeOH, 0ºC
Ph
CHO
Ph
CHO
Ph
7a
8
9'
9
Entry
8
Time (h)
Product (9/90)b
Yieldc (%)
eed (%) (9/90)
1
2
3
4
5
R0 = H 8a
8
12
12
12
12
9a/9a0 (55/45)
9k/9k0 (14/86)
9l/l0 (4/96)
68
65
28f
63
—
96/96
R0 = CH3 8b
R0 = Et 8c
R0 = Ph 8d
95/98e
g
—
9m/9m0 (<1/99)
—/99
—
h
R0 = COOEt 8e
—
a
Cinnamaldehyde 7a (0.25 mmol), 1-bromonitroalkane 8 (0.26 mmol), AcONa (0.26 mmol), 6 (0.025 mmol), and 1.0 ml methanol were used in the reaction.
The ratios of 9a/9a0, 9k/9k0–9m/9m0 were determined by GC analysis.
Isolated yield of combined 9 and 90.
b
c
d
e
f
The ee values were determined by chiral GC.
The ee value of 9k0 was determined by chiral GC analysis of the corresponding alcohol 100, obtained by NaBH4 reduction of 9k0.
The yield was determined by 1H NMR.
g
h
The ee values of 9l and 9l0 were not determined.
No nitrocyclopropane products could be isolated.
CP-Chirasil-DexCB (25 m ꢁ 0.25 mm, 0.25
lm, # CP7502). Enantio-
O
O
meric excesses of other nitrocyclopropane products were deter-
mined by HPLC using a Daicel Chiralcel AS-H column and eluting
with n-hexane/i-PrOH. The X-ray crystallographic data were
obtained with the Bruker Smart Apex II CCD X-ray diffractometer.
O
N
Br
R'
O
N
Br
R'
N
H
N
H
Ph
Ph
4.2. Typical experimental procedure for the catalyzed addition
I
II
of 1-bromonitroalkanes to a,b-unsaturated aldehydes
NO2
NO2
R'
R'
A mixture of diphenylprolinol triethylsilyl ether 6 (0.025 mmol)
and cinnamaldehyde 7 (0.25 mmol) in 1.0 ml methanol was stirred
for 5 min at room temperature, and was cooled to 0 °C. After
1-bromonitroalkane 8 (0.26 mmol) and AcONa (0.26 mmol) were
added, the reaction mixture was stirred for 8–24 h at 0 °C. The
solvent was evaporated under vacuum, and the residue was puri-
fied by flash column chromatography over silica gel (EtOAc/petro-
leum ether) to provide nitrocyclopropanes 9 and 90 as inseparable
mixtures.
Ph
CHO
Ph
CHO
9'
9
Scheme 3. Working model of asymmetric reaction of 1-bromonitroalkanes with
cinnamaldehyde.
4. Experimental
4.3. Spectroscopic data of nitrocyclopropanes 915
4.1. General details
4.3.1. Compound 9a
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.28 (d, J = 3.2 Hz,
1H), 7.35–7.26 (m, 5H), 5.33 (dd, J = 4.8, 3.6 Hz, 1H), 3.85 (dd,
J = 11.2, 4.8 Hz, 1H), 3.42 (dt, J = 11.2, 3.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d = 193.0, 130.2, 128.9, 128.7, 126.8, 62.4, 38.5,
All solvents were used as commercial anhydrous grade without
further purification. The flash column chromatography was carried
out over silica gel (230–400 mesh), purchased from Qingdao
Haiyang Chemical Co., Ltd. Optical rotations were measured on a
Perkin Elmer Model 341 digital polarimeter. Melting points were
recorded on an electrothermal digital melting-point apparatus.
1H and 13C NMR spectra were recorded on a Bruker AVANCE
400 MHz spectrometer as solutions in CDCl3. Chemical shifts in
1H NMR spectra are reported in parts per million (ppm, d) down-
field from the internal standard Me4Si (TMS, d = 0 ppm). Chemical
shifts in 13C NMR spectra are reported relative to the central line
of the chloroform signal (d = 77.0 ppm). High-resolution mass
spectra were obtained with the Thermo MAT 95XP mass spectrom-
eter or SHIMADZU LCMS-IT-TOF mass spectrometer. The low-reso-
lution mass spectra were obtained with the Thermo Trace GC
Ultra—DSQ II and Agilent 6120 (Quadrapole LC–MS) mass spec-
trometer. Infrared (IR) spectra were recorded on a Bruker Tensor
37 spectrophotometer. Data are represented as follows: frequency
of absorption (cmꢀ1), intensity of absorption (vs = very strong,
s = strong, m = medium, and w = weak). GC yields and enantio-
meric excesses of most nitrocyclopropane products were deter-
mined by GC (Agilent 6890N) with a Varian capillary column
36.1; IR (thin film) m
/cmꢀ1: 2855 (w), 1714 (s), 1634 (m), 1548
(s), 1499 (w), 1364 (s), 698 (m); HRMS (EI) calcd for C10H9NO3
(M+): 191.0582, found: 191.0585. The enantiomeric excess was
determined by GC using a Varian capillary column CP-Chirasil-
DexCB (carrier: N2, constant flow: 3.7 ml/min, oven temperature:
125 °C for 78 min, then 150 °C for 40 min); tR (major enantio-
mer) = 69.0 min, tR (minor enantiomer) = 72.7 min, 96% ee.
4.3.2. Compound 9a0
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.69 (d, J = 4.8 Hz,
1H), 7.42–7.17 (m, 5H), 4.82 (dd, J = 8.4, 4.8 Hz, 1H), 4.00 (dd,
J = 8.0, 4.8 Hz, 1H), 2.71 (ddd, J = 8.0, 8.0, 4.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d = 193.2, 133.2, 129.1, 128.53, 128.45, 66.5,
39.2, 32.5. The enantiomeric excess was determined by GC using
a Varian capillary column CP-Chirasil-DexCB (carrier: N2, constant
flow: 3.7 ml/min, oven temperature: 125 °C for 78 min, then 150 °C
for 40 min); tR (major enantiomer) = 69.0 min, tR (minor enantio-
mer) = 72.7 min, 96% ee.

J.-m. Zhang et al. / Tetrahedron: Asymmetry 20 (2009) 355–361
359
4.3.3. Compound 9b
by GC using a Varian capillary column CP-Chirasil-DexCB (carrier:
N2, constant flow: 3.7 ml/min, oven temperature: 150 °C); tR
(major enantiomer) = 34.1 min, tR (minor enantiomer) = 36.2 min,
94% ee.
Yellow solid. 1H NMR (400 MHz, CDCl3): d = 9.51 (d, J = 2.0 Hz,
1H), 8.20 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 5.35 (dd, J = 4.8,
4.0 Hz, 1H), 3.90 (dd, J = 11.2, 4.8 Hz, 1H), 3.62 (ddd, J = 11.2, 3.6,
2.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): d = 192.0, 147.8, 140.4,
127.9, 124.4, 62.4, 38.0, 35.7; IR (thin film)
m
/cmꢀ1: 2855 (w), 1713
4.3.9. Compound 9e
(s), 1604 (m), 1552 (s), 1519 (s), 1348 (s), 856 (m); HRMS (EI) calcd
for C10H8N2O5 (M+): 236.0433, found: 236.0435. The enantiomeric
excess was determined by HPLC with an AS-H column (n-hex-
ane/i-PrOH = 75/25, k = 220 nm, 1.0 ml/min); tR (major enantio-
mer) = 60.2 min, tR (minor enantiomer) = 66.8 min, 98% ee.
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.27 (d, J = 3.2 Hz,
1H), 7.16 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 5.25 (dd,
J = 4.8, 3.6 Hz, 1H), 3.78 (dd, J = 11.2, 4.8 Hz, 1H), 3.78 (s, 3H),
3.36 (dt, J = 11.2, 3.6 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d = 193.1, 159.6, 129.9, 122.1, 114.4, 62.7, 55.26, 38.7, 35.8; IR (thin
film) m
/cmꢀ1: 2926 (m), 2852 (m), 1714 (s), 1613 (m), 1549 (s),
4.3.4. Compound 9b0
1517 (s), 1366 (m), 1251 (m), 1180 (m), 834 (m); HRMS (EI) calcd
for C11H11NO4 (M+): 221.0688, found: 221.0685. The enantiomeric
excess was determined by GC using a Varian capillary column
CP-Chirasil-DexCB (carrier: N2, constant flow: 3.7 ml/min, oven
temperature: 150 °C); tR (major enantiomer) = 56.2 min, tR (minor
enantiomer) = 60.3 min, 89% ee.
Yellow solid. 1H NMR (400 MHz, CDCl3): d = 9.70 (d, J = 4.4 Hz,
1H), 8.24 (d, J = 8.8 Hz, 2H), 7.37 (d, J = 8.8 Hz, 2H), 4.88 (dd,
J = 8.4, 4.8 Hz, 1H), 4.08 (dd, J = 7.8, 4.4 Hz, 1H), 2.79 (ddd, J = 8.0,
8.0, 4.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d = 192.2, 147.9,
137.4, 129.9, 124.0, 66.0, 38.9, 31.4. The enantiomeric excess was
determined by HPLC with an AS-H column (n-hexane/i-PrOH = 75/
25, k = 220 nm, 1.0 ml/min); tR (major enantiomer) = 33.1 min, tR
(minor enantiomer) = 38.8 min, 92% ee.
4.3.10. Compound 9e0
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.65 (d, J = 4.8 Hz,
1H), 7.08 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 4.74 (dd,
J = 8.0, 4.8 Hz, 1H), 3.94 (dd, J = 8.0, 4.8 Hz, 1H), 3.80 (s, 3H), 2.64
(ddd, J = 8.0, 8.0, 4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d = 193.3, 159.8, 128.0, 125.1, 114.6, 66.6, 55.35, 39.3, 32.2. The
enantiomeric excess was determined by GC using a Varian capil-
lary column CP-Chirasil-DexCB (carrier: N2, constant flow:
3.7 ml/min, oven temperature: 150 °C); tR (major enantio-
mer) = 82.0 min, tR (minor enantiomer) = 87.4 min, 96% ee.
4.3.5. Compound 9c
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.34 (d, J = 2.0 Hz,
1H), 7.30 (d, J = 6.8 Hz, 2H), 7.18 (d, J = 6.4 Hz, 2H), 5.26 (dd,
J = 3.8, 2.8 Hz, 1H), 3.78 (dd, J = 8.8, 3.6 Hz, 1H), 3.44 (dt, J = 8.8,
2.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): d = 192.7, 134.4, 130.1,
129.0, 128.7, 62.4, 38.3, 35.6; IR (thin film)
m
/cmꢀ1: 2924 (m),
2854 (m), 1714 (s), 1551 (s), 1495 (m), 1364 (m), 1094 (m),
1015 (m), 827 (m); HRMS (EI) calcd for C10H8ClNO3 (M+):
225.0193, found: 225.0192. The enantiomeric excess was deter-
mined by GC using a Varian capillary column CP-Chirasil-DexCB
(carrier: N2, constant flow: 3.7 ml/min, oven temperature:
150 °C); tR (major enantiomer) = 49.6 min, tR (minor enantio-
mer) = 58.6 min, 91% ee.
4.3.11. Compound 9f
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.36 (d, J = 2.8 Hz,
1H), 7.29–7.12 (m, 4H), 5.28 (dd, J = 4.8, 3.6 Hz, 1H), 3.80 (dd,
J = 11.2, 4.8 Hz, 1H), 3.46 (dt, J = 11.2, 3.2 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d = 192.5, 135.18, 132.2, 130.2, 129.1, 128.85,
127.0, 62.2, 38.2, 35.6; IR (thin film) m
/cmꢀ1: 2925 (w), 2852 (w),
4.3.6. Compound 9c0
1714 (m), 1636 (s), 1549 (m), 1364 (m), 1082 (w), 784 (w); HRMS
(EI) calcd for C10H8ClNO3 (M+): 225.0193, found: 225.0195. The
enantiomeric excess was determined by GC using a Varian capil-
lary column CP-Chirasil-DexCB (carrier: N2, constant flow:
3.7 ml/min, oven temperature: 140 °C); tR (major enantio-
mer) = 74.9 min, tR (minor enantiomer) = 77.0 min, 96% ee.
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.64 (d, J = 4.0 Hz,
1H), 7.34 (d, J = 6.8 Hz, 2H), 7.12 (d, J = 6.8 Hz, 2H), 4.77 (dd,
J = 6.6, 4.0 Hz, 1H), 3.95 (dd, J = 6.0, 4.0 Hz, 1H), 2.66 (ddd, J = 6.4,
6.4, 3.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): d = 192.8, 134.5,
131.8, 129.3, 128.2, 66.3, 38.9, 31.7. The enantiomeric excess was
determined by GC using a Varian capillary column CP-Chirasil-
DexCB (carrier: N2, constant flow: 3.7 ml/min, oven temperature:
150 °C); tR (major enantiomer) = 77.5 min, tR (minor enantio-
mer) = 84.0 min, 95% ee.
4.3.12. Compound 9f0
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.67 (d, J = 4.4 Hz,
1H), 7.33–7.06 (m, 4H), 4.79 (dd, J = 8.4, 4.8 Hz, 1H), 3.96 (dd,
J = 7.8, 4.8 Hz, 1H), 2.69 (ddd, J = 8.0, 8.0, 4.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d = 192.6, 135.22, 134.9, 130.5, 128.89, 127.1,
125.1, 66.1, 38.8, 31.7. The enantiomeric excess was determined
by GC using a Varian capillary column CP-Chirasil-DexCB (carrier:
N2, constant flow: 3.7 ml/min, oven temperature: 140 °C); tR
(major enantiomer) = 108.8 min, tR (minor enantiomer) =
118.5 min, 96% ee.
4.3.7. Compound 9d
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.26 (d, J = 2.8 Hz,
1H), 7.17–7.09 (m, 4H), 5.27 (dd, J = 3.8, 3.2 Hz, 1H), 3.80 (dd,
J = 8.8, 4.0 Hz, 1H), 3.37 (dt, J = 9.2, 2.8 Hz, 1H), 2.32 (s, 3H); 13C
NMR (100 MHz, CDCl3): d = 193.1, 138.5, 129.6, 128.6, 126.7,
62.5, 38.6, 36.0, 21.1; IR (thin film) m
/cmꢀ1: 2925 (w), 1715 (s),
1549 (s), 1456 (w), 1363 (s), 1122 (m), 807 (w); HRMS (EI) calcd
for C11H11NO3 (M+): 205.0739, found: 205.0737. The enantiomeric
excess was determined by GC using a Varian capillary column
CP-Chirasil-DexCB (carrier: N2, constant flow: 3.7 ml/min, oven
temperature: 150 °C); tR (major enantiomer) = 24.7 min, tR (minor
enantiomer) = 25.9 min, 94% ee.
4.3.13. Compound 9g
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.43 (d, J = 2.0 Hz,
1H), 7.38–7.25 (m, 4H), 5.22 (dd, J = 4.0, 3.2 Hz, 1H), 3.73 (dd,
J = 8.6, 3.6 Hz, 1H), 3.56 (ddd, J = 8.8, 2.8, 2.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d = 192.1, 134.7, 130.5, 129.9, 127.9, 127.3,
127.0, 62.8, 37.6, 34.7; IR (thin film) m
/cmꢀ1: 2925 (m), 2853 (m),
4.3.8. Compound 9d0
1715 (s), 1550 (s), 1479 (m), 1441 (m), 1364 (s), 1131 (w), 755
(m); HRMS (EI) calcd for C10H8ClNO3 (M+): 225.0193, found:
225.0190. The enantiomeric excess was determined by GC using
a Varian capillary column CP-Chirasil-DexCB (carrier: N2, constant
flow: 3.7 ml/min, oven temperature: 150 °C); tR (major enantio-
mer) = 28.8 min, tR (minor enantiomer) = 27.4 min, 88% ee.
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.66 (d, J = 4.0 Hz,
1H), 7.21–7.00 (m, 4H), 4.76 (dd, J = 6.4, 3.6 Hz, 1H), 3.95 (dd,
J = 6.2, 3.6 Hz, 1H), 2.66 (ddd, J = 6.4, 6.4, 4.0 Hz, 1H), 2.34 (s, 3H);
13C NMR (100 MHz, CDCl3): d = 193.3, 138.6, 129.8, 128.5, 127.2,
62.7, 39.3, 32.4, 29.7. The enantiomeric excess was determined

360
J.-m. Zhang et al. / Tetrahedron: Asymmetry 20 (2009) 355–361
4.3.14. Compound 9g0
1413 (w), 1364 (s), 1026 (w), 710 (s); HRMS (ESI) calcd for
C9H9N2O3 [M+H]+: 193.0613, found: 193.0605. The enantiomeric
excess was determined by GC using a Varian capillary column
CP-Chirasil-DexCB (carrier: N2, constant flow: 3.7 ml/min, oven
temperature: 150 °C); tR (major enantiomer) = 47.0 min, tR (minor
enantiomer) = 50.6 min, 88% ee.
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.70 (d, J = 3.6 Hz, 1H),
7.45–7.08 (m, 4H), 4.75 (dd, J = 6.4, 4.0 Hz, 1H), 4.13 (dd, J = 6.4,
4.0 Hz, 1H), 2.65 (ddd, J = 6.6, 6.6, 3.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d = 193.2, 135.4, 131.0, 129.7, 128.6, 128.2, 127.2, 65.8,
38.1, 31.0. The enantiomeric excess was determined by GC using
a Varian capillary column CP-Chirasil-DexCB (carrier: N2, constant
flow: 3.7 ml/min, oven temperature: 150 °C); tR (major enantio-
mer) = 46.9 min, tR (minor enantiomer) = 50.2 min, 96% ee.
4.3.20. Compound 9j0
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.65 (d, J = 4.8 Hz,
1H), 8.51–8.49 (m, 2H), 7.47–7.44 (m, 1H), 7.31–7.28 (m, 1H),
4.85 (dd, J = 8.4, 4.8 Hz, 1H), 3.98 (dd, J = 7.6, 4.8 Hz, 1H), 2.72
(ddd, J = 8.0, 8.0, 4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d = 192.6, 149.7, 148.5, 134.1, 129.2, 123.7, 65.8, 38.3, 29.7. The
enantiomeric excess of 9j0 was determined after reducing to the
corresponding alcohol. The enantiomeric excess of the correspond-
ing alcohol was determined by GC using a Varian capillary column
CP-Chirasil-DexCB (carrier: N2, constant flow: 3.7 ml/min, oven
temperature: 165 °C); tR (major enantiomer) = 44.3 min, tR (minor
enantiomer) = 48.9 min, 86% ee.
4.3.15. Compound 9h
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.21 (d, J = 3.2 Hz,
1H), 7.33–6.84 (m, 4H), 5.15 (dd, J = 4.8, 3.6 Hz, 1H), 3.82 (s, 3H),
3.62 (dd, J = 10.8, 4.8 Hz, 1H), 3.38 (dt, J = 10.8, 3.6 Hz, 1H); 13C
NMR (100 MHz, CDCl3): d = 192.9, 157.5, 129.9, 129.7, 120.5,
118.7, 110.5, 62.6, 55.3, 37.8, 31.9; IR (thin film) m
/cmꢀ1: 2841
(w), 1714 (s), 1604 (m), 1547 (s), 1498 (m), 1364 (s), 1252 (s),
1025 (m), 755 (m); HRMS (EI) calcd for C11H11NO4 (M+):
221.0688, found: 221.0683. The enantiomeric excess was deter-
mined by GC using a Varian capillary column CP-Chirasil-DexCB
(carrier: N2, constant flow: 3.7 ml/min, oven temperature:
140 °C); tR (major enantiomer) = 62.8 min, tR (minor enantio-
mer) = 64.9 min, 89% ee.
4.3.21. Compound 9k
Colorless oil. 1H NMR (400 MHz, CDCl3): d = 9.29 (d, J = 6.0 Hz,
1H), 7.41–7.18 (m, 5H), 3.89 (d, J = 11.2 Hz, 1H), 3.27 (dd, J = 11.2,
5.6 Hz, 1H), 1.90 (s, 3H); 13C NMR (100 MHz, CDCl3): d = 195.2,
4.3.16. Compound 9h0
130.2, 129.4, 128.9, 128.4, 69.0, 39.7, 38.9, 12.8; IR (thin film) m/
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.67 (d, J = 5.2 Hz,
1H), 7.33–6.84 (m, 4H), 4.86 (dd, J = 8.0, 5.2 Hz, 1H), 4.02 (dd,
J = 8.0, 4.8 Hz, 1H), 3.84 (s, 3H), 2.73 (ddd, J = 8.0, 8.0, 5.2 Hz, 1H);
13C NMR (100 MHz, CDCl3): d = 194.3, 157.9, 129.9, 127.6, 121.3,
120.6, 110.7, 65.9, 55.4, 38.2, 29.5. The enantiomeric excess was
determined by GC using a Varian capillary column CP-Chirasil-
DexCB (carrier: N2, constant flow: 3.7 ml/min, oven temperature:
140 °C); tR (major enantiomer) = 86.9 min, tR (minor enantio-
mer) = 91.9 min, 95% ee.
cmꢀ1: 2921 (s), 2851 (s), 1713 (s), 1539 (s), 1450 (m), 1390 (w),
1351 (m), 1113 (m), 699 (m); HRMS (EI) calcd for C11H11NO3
(M+): 205.0739, found: 205.0736. The enantiomeric excess was
determined by GC using a Varian capillary column CP-Chirasil-
DexCB (carrier: N2, constant flow: 3.7 ml/min, oven temperature:
130 °C); tR (major enantiomer) = 27.8 min, tR (minor enantio-
mer) = 30.6 min, 95% ee.
4.3.22. Compound 9k0
Colorless oil. 1H NMR (400 MHz, CDCl3): d = 9.64 (d, J = 4.4 Hz,
1H), 7.39–7.20 (m, 5H), 4.19 (d, J = 8.0 Hz, 1H), 2.61 (dd, J = 8.0,
4.4 Hz, 1H), 1.54 (s, 3H); 13C NMR (100 MHz, CDCl3): d = 194.7,
131.8, 129.8, 128.9, 128.4, 72.5, 41.4, 37.2, 16.6. The enantiomeric
excess of 9i0 was determined after reducing to the corresponding
alcohol 100.
4.3.17. Compound 9i
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.39 (d, J = 4.0 Hz,
1H), 7.34–7.33 (m, 1H), 6.35–6.34 (m, 2H), 5.28 (dd, J = 4.2,
4.0 Hz, 1H), 3.67 (dd, J = 10.8, 4.4 Hz, 1H), 3.32 (dt, J = 10.8,
4.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): d = 192.4, 144.7, 142.9,
111.0, 110.2, 61.8, 38.1, 28.1; IR (thin film)
m
/cmꢀ1: 2924 (m),
2855 (m), 2361 (w), 1716 (s), 1550 (s), 1506 (w), 1365 (s), 1014
(m), 742 (s); HRMS (ESI) calcd for C8H6NO4 [MꢀH]ꢀ: 180.0297,
found: 180.0305. The enantiomeric excess was determined by GC
using a Varian capillary column CP-Chirasil-DexCB (carrier: N2,
constant flow: 3.7 ml/min, oven temperature: 125 °C); tR (major
enantiomer) = 22.4 min, tR (minor enantiomer) = 24.3 min, 89% ee.
4.3.23. Compound 9l0
Colorless oil. 1H NMR (400 MHz, CDCl3): d = 9.60 (d, J = 4.4 Hz,
1H), 7.38–7.23 (m, 5H), 4.13 (d, J = 8.0 Hz, 1H), 2.65 (dd, J = 8.0,
4.0 Hz, 1H), 1.68 (q, J = 7.6 Hz, 2H), 0.94 (t, J = 8.0 Hz, 3H); MS
(EI) m/e = 219.1 (M+), 190.1, 173.0, 145.0, 131.0, 128.0, 115.0,
105.0, 91.0, 76.9, 65.0, 51.0, 39.0, 29.0.
4.3.18. Compound 9i0
4.3.24. Compound 9m0
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.64 (d, J = 4.8 Hz,
1H), 7.34–7.33 (m, 1H), 6.38–6.36 (m, 2H), 4.90 (dd, J = 8.2,
4.4 Hz, 1H), 3.97 (dd, J = 7.6, 4.4 Hz, 1H), 2.80 (ddd, J = 8.0, 7.6,
4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): d = 192.5, 146.2, 142.7,
111.1, 108.9, 64.8, 37.5, 25.9. The enantiomeric excess was deter-
mined by GC using a Varian capillary column CP-Chirasil-DexCB
(carrier: N2, constant flow: 3.7 ml/min, oven temperature:
125 °C); tR (major enantiomer) = 26.7 min, tR (minor enantio-
mer) = 28.7 min, 92% ee.
White solid. ½a 2D0
ꢂ
¼ þ17:0 (c 1.0, CHCl3); Mp 131–132 °C; 1H
NMR (400 MHz, CDCl3): d = 9.74 (d, J = 4.0 Hz, 1H), 7.37–7.15 (m,
8H), 6.89–6.86 (m, 2H), 4.31 (d, J = 8.0 Hz, 1H), 3.23 (dd, J = 8.0,
4.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): d = 194.0, 131.6, 131.3,
130.3, 129.0, 128.7, 128.5, 128.1, 127.9, 80.1, 40.2, 37.0; IR (thin
film) m
/cmꢀ1: 2924 (w), 1703 (s), 1549 (s), 1448 (m), 1338 (m),
1127 (m), 1043 (m), 712 (m); HRMS (EI) calcd for C16H13NO3
(M+): 267.0895, found: 267.0890. The enantiomeric excess was
determined by GC using a Varian capillary column CP-Chirasil-
DexCB (carrier: N2, constant flow: 3.7 ml/min, oven temperature:
150 °C); tR (major enantiomer) = 48.2 min, tR (minor enantio-
mer) = 52.5 min, 99% ee.
4.3.19. Compound 9j
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 9.45 (d, J = 2.0 Hz,
1H), 8.56–8.55 (m, 2H), 7.55–7.52 (m, 1H), 7.28–7.24 (m, 1H),
5.30 (dd, J = 5.0, 4.0 Hz, 1H), 3.79 (dd, J = 11.0, 4.8 Hz, 1H), 3.54
(ddd, J = 11.0, 3.8, 2.0 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d = 192.5, 150.1, 149.5, 136.1, 126.3, 123.4, 62.0, 37.8, 33.9; IR (thin
4.4. Reduction of 9k/9k0 with NaBH4
A mixture of 9k/9k0 (dr = 14/86) (10 mg) and NaBH4 (8 mg) was
mixed in ethanol (1 ml). After stirring for 15 min at room temper-
film)
m
/cmꢀ1: 2924 (w), 2854 (w), 2349 (m), 1710 (s), 1547 (s),

J.-m. Zhang et al. / Tetrahedron: Asymmetry 20 (2009) 355–361
361
Aggarwal, V. K.; Winn, C. L. Acc. Chem. Res. 2004, 37, 611; (d) Pellissier, H.
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ature, the solution was treated with saturated aqueous NaHCO3.
The mixture was extracted with CH2Cl2 (3 ml ꢁ 2). The organic
layer was separated and filtered through a silica gel plug. Alcohol
10/100 was obtained after evaporation of the solvent.
4. For the selected recent publications, see: (a) Ibrahem, I.; Zhao, G.-L.; Rios, R.;
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4.4.1. Compound 10
Colorless oil. 1H NMR (400 MHz, CDCl3): d = 7.36–7.19 (m, 5H),
3.94 (dd, J = 11.6, 6.8 Hz, 1H), 3.53 (dd, J = 11.8, 8.4 Hz, 1H), 3.55 (d,
J = 10.8 Hz, 1H), 2.77 (ddd, J = 10.8, 8.4, 6.8 Hz, 1H), 1.77 (s, 1H),
1.62 (s, 3H); 13C NMR (100 MHz, CDCl3): d = 132.4, 129.9, 128.8,
127.7, 67.2, 58.9, 36.8, 34.6, 12.3; IR (thin film) m
/cmꢀ1: 3421(s),
2926 (w), 1604 (w), 1531 (s), 1449 (m), 1390 (m), 1353 (m),
1118 (m), 1031 (m), 699 (m); HRMS (EI) calcd for C11H13NO3
(M+): 207.0895, found: 207.0891.
4.4.2. Compound 100
Colorless oil. 1H NMR (400 MHz, CDCl3): d = 7.36–7.19 (m, 5H),
4.17 (dd, J = 12.2, 5.6 Hz, 1H), 3.95 (dd, J = 12.0, 8.4 Hz, 1H), 3.56 (d,
J = 8.4 Hz, 1H), 2.15 (ddd, J = 8.4, 8.4, 5.6 Hz, 1H), 2.08 (s, 1H), 1.50
(s, 3H); 13C NMR (100 MHz, CDCl3): d = 134.1, 128.7, 128.6, 127.8,
70.0, 59.9, 36.2, 36.1, 17.1. The enantiomeric excess was deter-
mined by GC using a Varian capillary column CP-Chirasil-DexCB
(carrier: N2, constant flow: 3.7 ml/min, oven temperature:
140 °C); tR (major enantiomer) = 65.1 min, tR (minor enantio-
mer) = 70.3 min, 98% ee.
8. Asymmetric synthesis of nitrocyclopropanes via the reaction of nitroalkyl
carbene with alkenes, see: (a) Charette, A. B.; Wurz, R. P. J. Mol. Catal. A 2003,
196, 83; (b) Wurz, R. P.; Charette, A. B. Org. Lett. 2003, 5, 2327; (c) Moreau, B.;
Charette, A. B. J. Am. Chem. Soc. 2005, 127, 18014; (d) Zhu, S.; Perman, J. A.;
Zhang, X. P. Angew. Chem., Int. Ed. 2008, 47, 8460.
9. Asymmetric synthesis of nitrocyclopropanes via conjugate addition of
a -
Acknowledgments
halogenated nucleophiles to nitroolefins: McCooey, S. H.; McCabe, T.; Connon,
S. J. J. Org. Chem. 2006, 71, 7494.
We thank the National Natural Science Foundation of China
(No. 20772160), NCET plan of Ministry of Education of China,
Guangzhou Bureau of Science and Technology for the financial
support of this study.
10. For the review of activation of
a, b -unsaturated aldehydes and ketones with
chiral secondary amines, see: (a) Erkkilä, A.; Majander, I.; Pihko, P. M. Chem.
Rev. 2007, 107, 5416; (b) Ouellet, S. G.; Walji, A. M.; Macmillan, D. W. C. Acc.
Chem. Res. 2007, 40, 1327; (c) Walji, A. M.; Macmillan, D. W. C. Synlett 2007,
1477; (d) Mielgo, A.; Palomo, C. Chem. Asian J. 2008, 3, 922; (e) Yu, X.; Wang, W.
Org. Biomol. Chem. 2008, 6, 2037; (f) Macmillan, D. W. C. Nature 2008, 455, 304.
11. Asymmetricconjugateadditionofbromonitromethane toenones, see:(a)Hansen,
H. M.; Longbottom, D. A.; Ley, S. V. Chem. Commun. 2006, 4838; (b) Wascholowski,
V.; Hansen, H. M.; Longbottom, D. A.; Ley, S. V. Synthesis 2008, 1269.
12. Vesely, J.; Zhao, G.-L.; Bartoszewicz, A.; Córdova, A. Tetrahedron Lett. 2008, 49,
4209.
References
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14. The crystallographic data (excluding structure factors) of 9b0 are deposited
with the Cambridge Crystallographic Data Center as Supplementary
Publication No. CCDC 710653. Copies of the data can be obtained, free of
charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax:
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15. The diastereoisomers 9 and 90 are inseparable by column chromatography.
Their 1H NMR and 13C NMR data were obtained by analyzing the NMR spectra
of 9/90 mixtures. However IR and MS spectroscopic data could not be assigned
individually for them.