Kinetic resolution of activated nitroallylic acetates with aldehydes and ketones through a conjugate addition-elimination SN2′ process

Article abstract of DOI:10.1002/ejoc.201101162

A unique organocatalytic kinetic resolution (KR) of nitroallylic acetates has been developed. A variety of racemic nitroallylic acetates (1a-n) were resolved with chiral enamines formed in situ from the reaction of aldehydes and ketones with organocatalys

Full text of DOI:10.1002/ejoc.201101162

FULL PAPER
DOI: 10.1002/ejoc.201101162
Kinetic Resolution of Activated Nitroallylic Acetates with Aldehydes and
Ketones through a Conjugate Addition–Elimination SN2Ј Process
Raju Jannapu Reddy,[a] Pei-Hsun Lee,[a] Dhananjay R. Magar,[a] Jung-Hsuan Chen,[a] and
Kwunmin Chen*[a]
Keywords: Aldehydes / Diastereoselectivity / Enantioselectivity / Ketones / Kinetic resolution / Organocatalysis
A unique organocatalytic kinetic resolution (KR) of nitroal-
lylic acetates has been developed. A variety of racemic nitro-
allylic acetates (1a–n) were resolved with chiral enamines
formed in situ from the reaction of aldehydes and ketones
with organocatalyst 2b (2.5 mol-%) and 14c (20 mol-%),
respectively, through an interesting SN2Ј reaction. The
densely functionalized products 3–5 were obtained with high
to excellent levels of stereoselectivities (up to Ͼ99:1dr and
Ͼ99%ee) in good to high chemical yields. The unreactive
starting substrates 1a–n were recovered with good to high
optical purity (up to 98%ee). The scope and generality of the
kinetic resolution was expanded to include a wide range of
nitroallylic acetates with various aldehydes and ketones as
the donor sources. The absolute stereochemistry of the func-
tionalized products and the unreacted substrate were deter-
mined. Synthetic application was demonstrated when (S)-cit-
ronellal was treated with rac-1a in the presence of 2b to give
12 as a single diastereomer, which was further cyclized to
give a tetrasubstituted cyclohexane derivative 13 with excel-
lent stereoselectivity. Transition-state models were proposed
to account for the stereochemical bias in the KR process.
the generation of diverse functionalities with new stereo-
genic centers in the final products has not yet been fully
explored.[8]
Introduction
Apart from asymmetric synthesis, kinetic resolution
(KR) is a conventional protocol that enables the prepara-
tion of enantiomerically enriched substances from racemic
starting materials.[1] Biocatalytic approaches require the use
of hydrolytic enzymes such as proteases, lipases or acylases
for specific racemic substrates.[2] The use of low molecular
weight chiral catalysts for KR processes has recently
emerged as a practical approach.[3] The process involves a
chiral agent that promotes the selective reaction of one en-
antiomer based on a difference in the reaction rate.[1d] In
the best scenario, both the product and the unreacted enan-
tiomeric substrate are obtained with high optical purity.
Generally, the KR process is performed without the cre-
ation of new stereogenic centers in the products.[4] However,
some metal-catalyzed KR procedures have been realized
with the creation of new stereogenic centers in the products
with high asymmetric induction.[5] Central to this challenge
is the identification of a suitable class of substrate. The race-
mic multifunctional nitroallylic acetates seem to fulfill this
criterion. Recently, organocatalysis has been recognized as
the third powerful protocol to complement enzymes and
transition-metal complexes in asymmetric synthesis.[6] Al-
though organocatalytic KR variants have been reported,[7]
Motivated by our recent research interest in organocata-
lytic asymmetric transformations,[9] we envisioned that race-
mic nitroallylic acetates such as rac-1 could serve as a good
Michael type acceptor for enantioselective conjugate ad-
dition–elimination reactions. The functionalized racemic ni-
troallylic acetates are readily available through the Morita–
Baylis–Hillman reaction between ethyl glyoxylate and nitro-
alkenes, followed by acetylation.[10] Examination of the
structural array reveals that they are promising substrates
for organocatalytic transformations.[11] A diverse range of
enantioselective transformations can be anticipated. For ex-
ample, kinetic resolution of racemic nitroallylic acetates
with a nucleophilic partner through the Michael type reac-
tion may be possible. Various organocatalysts, including l-
proline (2a), diarylprolinol trimethylsilyl ether[12] (2b, 2c),
thiourea catalyst (2d) and camphor-based pyrrolidine (2e,
2f), have proven to be effective in enamine catalysis in re-
cent years (Figure 1).
The resolution of racemic nitroallylic acetate 1 is of suf-
ficient quality to warrant practical significance, and KR
processes can facilitate the generation of both the multi-
functionalized product and unreacted substrate in optically
enriched form.[13] Following our previous results relating to
organocatalytic KR processing using aldehydes as the nu-
cleophilic partner,[14] in this paper, we extend our studies
to the organocatalytic kinetic resolution of various racemic
nitroallylic acetates with branched and linear aldehyde do-
[a] Department of Chemistry, National Taiwan Normal University,
Taipei, Taiwan 116, Republic of China
Fax: +886-2-29324249
E-mail: kchen@ntnu.edu.tw
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101162.
Eur. J. Org. Chem. 2012, 353–365
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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K. Chen et al.
FULL PAPER
high chemical yields and good to excellent levels of optical
purity (for substrate scope and compound characterization,
see the Supporting Information).
Figure 1. Organocatalysts examined for the kinetic resolution of
racemic nitroallylic acetates with aldehyde donors.
nors. Both the products 3 and 4 and the remaining substrate
(+)-1 were obtained in high chemical yields and good to
excellent levels of optical purity with 2.5 mol-% catalyst 2b
(Scheme 1). Furthermore, cyclic ketones were explored to
resolve racemic nitroallylic acetate 1 in the presence of a
sulfide-linked pyrrolidinyl-camphor organocatalyst 14c.
Interestingly, the opposite enantiomeric substrate (–)-1 re-
mained with high optical purity. The prominent feature of
the organocatalytic conjugate addition–elimination process
is that it provides multi-functionality of products 3–5 with
two newly generated stereogenic centers.
Scheme 2. Substrate scope for the organocatalytic kinetic resolu-
tion of racemic nitroallylic acetates with various aldehyde donors.
The structures of the multifunctional products were fully
1
characterized by IR, H and 13C NMR spectroscopy and
by HRMS analyses. The geometry of the trisubstituted
nitroalkenes of products (3a–m and 4a–q) was established
1
on the basis of H NMR analysis. In the 1H NMR spectra,
a singlet signal at approximately δ = 6.80 ppm indicated ex-
clusive formation of the Z-trisubstituted nitroalkenes.[15,16]
For absolute stereochemistry determination, the products
(3a and 4b) were further transformed into their correspond-
ing primary alcohols. Treatment of the nearly optically pure
nitroallylic aldehyde 3a with NaBH4 in MeOH at 0 °C gave
a diastereomeric mixture of saturated nitroester (Scheme 3).
Not unexpectedly, the activated double bond was reduced
and resulted in a diastereoselective ratio of 70:30. Similar
results were obtained when optically enriched 4b was used
under the same reaction conditions (80:20dr). Reaction of
primary alcohol 6 with camphanyl chloride in the presence
Scheme 1. Organocatalytic kinetic resolution of racemic nitroallylic
acetates 1 with aldehydes and cyclic ketones.
Results and Discussion
We began this project with the identification of a suitable of 4-(N,N-dimethylamino)pyridine (DMAP) gave the de-
organocatalyst for the kinetic resolution process. The race- sired adduct 8 as a colorless solid as a diastereomeric 75:25
mic nitroallylic acetate 1a and isovaleraldehyde were used mixture. Fortunately a single crystal of the major isomer
as model substrates (Scheme 2). After extensive work, the was obtained that was suitable for X-ray crystallographic
diphenylprolinol trimethylsilyl ether 2b turned out to be the data analysis.[17] The absolute configuration of the newly
catalyst of choice for the KR reaction. Variations of the generated stereocenters of the camphanyl derivative 8 was
nucleophilic partners, catalyst loadings, concentration, and determined to be (R,S,S) by X-ray structure analysis.
temperature, as well as the effect of additives were examined Accordingly, the absolute configuration of product 3a was
to optimize the reaction conditions. The optimum condi- established as (R,S), analogously to 8.
tions were realized by using 1.5 equiv. of aldehyde and
Next, determination of the absolute stereochemistry of
2.5 mol-% catalyst 2b at 0 °C, which afforded the most the recovered nitroallylic alcohol was carried out
promising results. In addition, our studies were extended to (Scheme 4). Toward this, high optical purity (+)-1a (94%ee)
include other linear aldehydes, such as valeraldehyde, butyr- was treated with Sm(OTf)3 in MeOH to give the allylic
aldehyde, and 3-phenylpropionaldehyde. Both the products alcohol 9 in 70% chemical yield with retention of stereo-
3 and 4 and the remaining substrate (+)-1 were obtained in chemical information. Treatment of the allylic alcohol un-
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Kinetic Resolution of Activated Nitroallylic Acetates
(11) reacted smoothly with rac-1a to afford the desired ad-
duct 12 as a single diastereomer in 34% chemical yield. The
recovered acetate (+)-1a was obtained with 38% yield and
an optical purity of 84%ee at 53% conversion (Scheme 5).
The adduct 12 was further treated with InBr3 for the cycli-
zation in toluene to give the desired tetrasubstituted cyclo-
hexane derivative 13 with 62% yield and excellent diastereo-
selectivity. The carbonyl ene-reaction was initiated by acti-
vation of the carbonyl group by the Lewis acid, followed by
cyclization to give the six-membered ring. The structure of
1
13 was fully characterized by IR, H and 13C NMR, and
HRMS analyses. The structure and stereochemistry of 13
was further confirmed by NOE studies. On the basis of the
NOE experiments (see the Supporting Information), the rel-
ative stereochemistry (C3 and C4) of 13 could be ascer-
tained; in particular, NOE correlations were observed be-
tween Ha–Hb and Hb–Hc. The strong NOE correlation be-
tween the olefinic proton and the aromatic proton further
established the Z-geometry of the product.
Scheme 3. Synthesis of alcohols 6 and 7 and the derived camphanyl
ester 8.
der the standard Mosher ester formation protocol (Mosher
acid, N,N-dicyclohexylcarbodiimide (DCC), DMAP,
CH2Cl2) resulted in the formation of two diastereomeric
1
esters in a ratio of 3:2 (determined by H NMR analysis).
Although the vinyl protons of the two diastereomers were
distinguishable (δ = 8.52 and 8.44 ppm, respectively), no de-
finitive conclusion could be drawn from the epimerization
reaction. Interestingly, the coupling of allylic alcohol 9 with
4-nitrobenzoic acid worked well. The product (E)-1-ethoxy-
4-nitro-1-oxo-3-phenylbut-3-en-2-yl-4-nitrobenzoate
(10)
could be recrystallized from CHCl3, allowing single-crystal
X-ray analysis (Scheme 4).[17]
Scheme 5. Synthesis of tetrasubstituted cyclohexane derivative 13
from (S)-citronellal (11).
To further extend the utility of this KR approach, cyclo-
hexanone was used as the nucleophilic partner in the KR
process. Unfortunately, no desired product was obtained
when cyclohexanone and nitroallylic acetate 1a were used
in the presence of 2b under the optimum reaction condi-
tions. An alternative catalytic system thus needed to be de-
veloped for the resolution of racemic nitroallylic acetate 1a
with cyclohexanone. We have recently demonstrated that
sulfide-linked pyrrolidinyl-camphor organocatalysts 14a–d,
15a, 15b, and 16 are capable of catalyzing the Michael ad-
dition of cyclohexanone to alkylidene malonates as sub-
strates.[9d] Based on the previous results, the pyrrolidinyl-
Scheme 4. Synthesis of nitroallylic alcohol derived benzoate 10 and
its X-ray crystal structure.
Citronellal is a useful chiral starting material for the syn- camphor linked organocatalysts 14–16 were screened for
thesis of important intermediates.[18] For example, conju- the kinetic resolution of rac-1a with cyclohexanone as a do-
gate addition of citronellal with methyl vinyl ketone[18a–18c] nor.
and vinyl bis(sulfone) under basic conditions have been de-
Initially, the reaction was carried out under neat condi-
veloped.[18d] More recently, we have successfully employed tions with 20 mol-% catalyst loading at 0 °C in the presence
citronellal as an excellent donor partner with trans-β-nitro- 2.0 equiv. AcOH; under these conditions, the Michael ad-
styrene[9e] and azodicarboxylate.[9f] In light of this, we se- duct 5a was obtained with good enantioselectivity and the
lected (S)-citronellal (11) as a donor partner with rac-1a recovered acetate was obtained with low optical purity
in the presence of organocatalyst 2b (2.5 mol-%) under the when organocatalyst 14a was used (Table 1, Entry 1). No-
optimal reaction conditions. Remarkably, (S)-citronellal tably, the trans-4-hydroxy pyrrolidinyl-camphor derivatives
Eur. J. Org. Chem. 2012, 353–365
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K. Chen et al.
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Table 1. Organocatalyst screening for the kinetic resolution of rac-1a with cyclohexanone.[a]
Entry
Catalyst
Time
[d]
Conversion
[%][b]
5a
(–)-1a
% Yield[c]
% ee[d]
% Yield[c]
% ee[d]
1
2
3
4
5
6
7
14a
14b
14c
14d
15a
15b
16
3.5
5.5
2
6.5
5.5
1
30
42
41
44
33
19
21
21
36
34
39
25
12
13
89
93
94
91
87
86
92
40
28
35
24
16
19
15
40
60
59
71
95
82
89
6.5
[a] Reagents and conditions: (Ϯ)-1 (0.15 mmol), cyclohexanone (0.45 mmol), organocatalyst (20 mol-%), AcOH (0.3 mmol, 2.0 equiv.),
neat conditions, 0 °C. [b] Determined by 1H NMR analysis of the crude reaction mixture. [c] Isolated yield. [d] Determined by chiral
HPLC analysis.
14b and 14c were found to be effective for this KR process, used, and proceeded slowly in Et2O and EtOAc (Table 2,
giving 5a with high chemical yields and enantioselectivities Entries 1–5). Excellent enantioselectivities were obtained
(Table 1, Entries 2 and 3). However, moderate optical purity when CH2Cl2 and toluene were used as solvent, but low
of the recovered nitroallylic acetate (–)-1a was observed. optical purities of the unreactive substrates were found
The reactivity decreased when the corresponding TBDPS
ether derivative 14d was used (Table 1, Entry 4). We next
studied the cis-4-hydroxy-derived organocatalyst 15a. Al-
though excellent optical purity of the unreacted nitroallylic
acetate (–)-1a was observed, the reaction proceeded slug-
gishly (Table 1, Entry 5). On the other hand, the reactivity
was improved when cis-4-amino derivative 15b was used,
but the optical enrichment of the recovered substrate (–)-1a
decreased (Table 1, Entry 6). The stereochemical outcomes
were found to be good when the reaction was carried out
in the presence of the corresponding thiourea derivative 16,
although the reactivity dropped significantly (Table 1, En-
try 7). It is interesting to note that the opposite enantio-
meric nitroallylic acetate (–)-1a was recovered when cyclo-
hexanone was used as the nucleophilic partner instead of
aldehydes. It seems that the C4 functional group (OH, NH2,
and thiourea) in the pyrrolidine ring plays a role in con-
trolling the stereoselectivity, whereas the C2 functionality
(camphor numbering) showed little influence. The reaction
proceeded smoothly in the presence of 2.0 equiv. AcOH rel-
ative to the substrate.
Table 2. Solvent screening for the kinetic resolution of (Ϯ)-1a with
cyclohexanone.[a]
Entry Solvent Time Conv.
5a
(–)-1a
[d]
[%][b] % Yield[c] % ee[d] % Yield[c] % ee[d]
1
2
3
4
5
6
7
8
MeOH
CH3CN
THF
4
4
4
4
4
4
2
1
trace
trace
trace
8
10
26
–
–
–
–
–
17
23
37
–
–
–
–
–
99
99
94
–
–
–
–
–
33
26
36
–
–
–
–
–
10
20
66
Et2O
EtOAc
CH2Cl2
toluene
MTBE
35
59
We next examined the solvent effects using the trans-4-
hydroxy group derived catalyst 14c for the kinetic resolu-
tion. The reaction failed to proceed when polar solvents
[a] Reagents and conditions: (Ϯ)-1a (0.15 mmol), cyclohexanone
(0.45 mmol), organocatalyst (20 mol-%), AcOH (2.0 equiv.), 0 °C.
[b] Determined by 1H NMR analysis of the crude reaction mixture.
(MeOH and CH3CN) and tetrahydrofuran (THF) were [c] Isolated yield. [d] Determined by chiral HPLC analysis.
356 Eur. J. Org. Chem. 2012, 353–365
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Kinetic Resolution of Activated Nitroallylic Acetates
(Table 2, Entries 6 and 7). Finally, the reaction was found yield and 74%ee. On the other hand, the use of dihydro-
to proceed smoothly to give 5a with excellent enantio- 2H-thiopyran-4(3H)-one (18) gave the product 18a with
selectivity and (–)-1a was recovered with good optical pu- 94%ee and acetate (–)-1a with only 22%ee.
rity when methyl tert-butyl ether (MTBE) was used
(Table 2, Entry 8).
With the optimum reaction conditions realized, various
substrates were studied to explore the generality of the KR
process. Gratifyingly, all the nitroallylic acetates rac-1 re-
acted smoothly to afford the desired products 5 with high
enantioselectivities. The recovered substrate (–)-1 was ob-
tained with moderate to good optical purity, as depicted
in Table 3. Generally, substituents on the aryl group in the
starting acetate did not have any significant effect on the
enantioselectivities of the products. This indicates that the
Scheme 6. Organocatalytic kinetic resolution of racemic nitroallylic
structural scaffold of the organocatalyst dictates the transi-
tion-state conformation of the SN2Ј reaction. The enantio-
selectivities of the recovered acetates were also minimally
influenced by the substituent. The use of electron-releasing
substituents in the aryl group gave the desired products
with high enantioselectivities and high yields (Table 3, En-
tries 2–4 and 9). Regardless the position of the halide sub-
stituent on the aryl group, comparably high stereoselectivi-
ties were observed (Table 3, Entries 5–8 and 10).
acetate (Ϯ)-1a with ketones 17 and 18.
The stereochemical bias of the kinetic resolution process
is unclear at this moment but can be rationalized by invok-
ing the transition-state conformations I–IV as shown Fig-
ure 2. The nucleophilic enamines were first formed from the
reaction of the organocatalyst and the carbonyl group (al-
dehyde or ketone). In the case of diphenylprolinol trimeth-
ylsilyl ether (2b) derived enamine, the trans double bond is
oriented away from the bulky diphenyl group. The starting
nitroallylic acetate approaches from the face opposite to the
bulky diphenyl group, with the nitro group toward the ni-
trogen atom of the pyrrolidine ring.[19] The enamine prefer-
entially attacks the (–)-(S)-nitroallylic acetate 1a from the
Si face through the acyclic synclinal geometry (TS-I).[20] In
contrast, transition state TS-II is energetically unfavored
because of steric repulsion between the (+)-(R)-nitroallylic
acetate 1a and the enamine. Similarly, the enamine was gen-
erated from cyclohexanone and trans-4-hydroxy pyrrolidine
derived organocatalyst 14c with the camphor structural
moiety oriented inward. The starting nitroallylic acetate
would then approach from the less hindered face of the en-
amine intermediate. In addition to the electrostatic interac-
tion between the nitrogen atom of the pyrrolidine ring and
the nitro group, the hydrogen bond stabilization between
the 4-hydroxyl and nitro groups is also a significant factor.
Table 3. Substrate scope of the kinetic resolution of rac-1a–h, 1o,
and 1p with cyclohexanone.[a]
Entry
1
Conv.
[%][b]
5
(–)-1
% Yield[c] % ee[d]
% Yield[c] % ee[d]
1
2
3
4
5
6
7
8
9
10
1a
1b
1c
1d
1e
1f
1g
1h
1o
1p
43
43
41
43
43
34
31
36
44
29
5a
5b
5c
5d
5e
5f
5g
5h
5o
5p
37
37
35
37
37
26
22
28
40
20
94
95
96
95
93
94
93
94
94
93
1a
1b
1c
1d
1e
1f
1g
1h
1o
1p
36
43
38
40
27
23
29
30
35
25
66
63
53
65
62
61
42
65
89
37
[a] Reagents and conditions: rac-1a–h, 1o, 1p (0.15 mmol), cyclo-
hexanone (0.45 mmol), 14c (20 mol-%), AcOH (2.0 equiv.), MTBE,
1
0 °C, 1 d. [b] Determined by H NMR analysis of the crude reac-
tion mixture. [c] Isolated yield. [d] Determined by chiral HPLC
analysis.
Further experiments were carried out to resolve the race-
mic nitroallylic acetate 1a using different cyclic ketones
(Scheme 6). Use of dihydro-2H-pyran-4(3H)-one (17) as a
Figure 2. Proposed mechanism for the kinetic resolution of racemic
donor gave the desired product 17a with 26% chemical nitroallylic acetate 1a and derived enamines.
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K. Chen et al.
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1196, 1019 cm–1. 1H NMR (400 MHz, CDCl3): δ = 9.90 (d, J =
2.0 Hz, 1 H), 7.25 (d, J = 7.8 Hz, 2 H), 7.12 (d, J = 8.0 Hz, 2 H),
6.72 (s, 1 H), 5.63 (d, J = 11.2 Hz, 1 H), 4.38–4.30 (m, 2 H), 3.78–
3.72 (m, 1 H), 2.31 (s, 3 H), 1.91 (sept., J = 7.1 Hz, 1 H), 1.37 (t,
J = 7.2 Hz, 3 H), 1.14 (d, J = 7.0 Hz, 3 H), 0.93 (d, J = 7.0 Hz, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 203.7, 164.3, 164.2,
137.9, 132.8, 129.7, 128.7, 120.6, 61.9, 57.7, 40.2, 28.0, 21.7, 21.0,
16.8, 14.0 ppm. HRMS (FAB+): calcd. for C18H24NO5 [M + H]+
334.1654; found 334.1653. Diastereomeric ratio: Ͼ99:1; enantio-
meric excess was determined by HPLC (Chiralpak AS-H; iPrOH/
hexanes, 2:98; flow rate = 0.5 mL/min; λ = 254 nm): tR = 14.1
(minor), 18.0 (major) min. 1b (recovery acetate): Spectroscopic data
were in agreement with the racemic substrate 1b. Yield: 42%
(25.8 mg); enantiomeric excess was determined by HPLC (Chi-
Therefore, the energetically favored transition-state (TS-III)
was formed readily between (+)-(R)-nitroallylic acetate 1a
and enamine. The SN2Ј process was then initiated by
nucleophilic addition of the enamine on the Michael
acceptor. The steric interaction between the ester group in
(–)-(S)-nitroallylic acetate 1a and the camphor scaffold may
account for the unfavored formation of transition state IV.
Conclusions
We have successfully developed a novel and practical or-
ganocatalytic process for the resolution of racemic nitro-
allylic acetates with aldehydes and ketones through a conju- ralpak AD-H; iPrOH/hexanes, 5:95; flow rate = 0.5 mL/min; λ =
254 nm): tR = 17.5 (minor), 20.4 (major) min.
gate addition–elimination process. The kinetic resolution
process affords densely functionalized products with recov-
ery of the less reactive starting substrate. In the case of alde-
hydes, excellent diastereo- and enantioselectivities (up to
99:1dr and 99%ee) of the products and good to high levels
of optical purity (up to 98%ee) of starting materials (+)-
1a–m were recovered in the presence of organocatalyst 2b.
When cyclic ketones were used in the presence of 14c, high
to excellent diastereo- and enantioselectivities (up to 99:1dr
and 96%ee) of the products and good to high levels of
optical purity (up to 89%ee) of (–)-1a–h, 1o, and 1p were
recovered. To the best of our knowledge, this is the first
example of nitroallylic acetates being resolved using the
prominent diphenylprolinol trimethylsilyl ether 2b and 14c
as catalysts. The KR process proceeded smoothly with low
catalyst loading (2.5 mol-%) of 2b when aldehydes were
used. The reaction proceeded in a highly stereospecific fash-
ion, with both enantiomerically enriched products being
obtained when both enantiomeric catalysts were used. We
also demonstrated that organocatalytic kinetic resolution of
rac-1a with (S)-citronellal afforded 12 as a single dia-
stereomer. Further transformation of 12 was carried out to
give the tetrasubstituted cyclohexane derivative 13 with ex-
cellent stereoselectivity.
(4S,5R)-Ethyl 5-Formyl-4-(3-methoxyphenyl)-6-methyl-3-nitrohept-
2(Z)-enoate (3c): According to the general procedure, the resolution
of rac-1c (0.2 mmol, 64.6 mg) with isovaleraldehyde (0.3 mmol,
32 μL) in toluene (0.4 mL) and 2b (1.0 m in toluene, 0.005 mmol,
5 μL) at 0 °C for 15 h. Yield: 40% (28.0 mg) at 53% conversion.
IR (CH Cl ): ν = 2992, 2988, 1762, 1659, 1535, 1478, 1370, 1258,
˜
2
2
1195, 1014 cm–1. 1H NMR (400 MHz, CDCl3): δ = 9.90 (d, J =
1.7 Hz, 1 H), 7.24 (dd, J = 4.3, 8.2 Hz, 1 H), 6.95 (d, J = 7.9 Hz,
2 H), 6.81 (dd, J = 2.0, 7.2 Hz, 1 H), 6.75 (s, 1 H), 5.64 (d, J =
11.3 Hz, 1 H), 4.38–4.30 (m, 2 H), 3.78 (s, 3 H), 3.77–3.72 (m, 1
H), 1.92 (sept., J = 7.0 Hz, 1 H), 1.37 (t, J = 7.1 Hz, 3 H), 1.17 (d,
J = 7.1 Hz, 3 H), 0.93 (d, J = 7.1 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 203.5, 164.2, 163.8, 159.9, 137.4, 130.0,
121.08, 121.05, 114.9, 113.1, 61.9, 57.7, 55.2, 40.4, 28.1, 21.8, 16.9,
14.0 ppm. HRMS (FAB+): calcd. for C18H24NO6 [M + H]+
350.1604; found 350.1595. Diastereomeric ratio: Ͼ99:1; enantio-
meric excess was determined by HPLC (Chiralcel OD-H; iPrOH/
hexanes, 5:95; flow rate = 0.5 mL/min; λ = 254 nm): tR = 13.8
(major), 19.0 (minor) min. 1c (recovery acetate): Spectroscopic data
were in agreement with racemic substrate 1c. Yield: 38% (24.5 mg);
enantiomeric excess was determined by HPLC (Chiralcel OD-H;
iPrOH/hexanes, 5:95; flow rate = 1.0 mL/min; λ = 254 nm); tR
10.4 (major), 11.6 (minor) min.
=
(4S,5R)-Ethyl 5-Formyl-4-(4-methoxyphenyl)-6-methyl-3-nitrohept-
2(Z)-enoate (3d): According to the general procedure, the resolu-
tion of rac-1d (0.2 mmol, 64.6 mg) with isovaleraldehyde
(0.3 mmol, 32 μL) in toluene (0.4 mL) and 2b (1.0 m in toluene,
0.005 mmol, 5 μL) at 0 °C for 15 h. Yield: 30% (21.0 mg) at 45%
Experimental Section
conversion. IR (CH Cl ): ν = 2996, 2980, 1768, 1669, 1536, 1468,
˜
2
2
1365, 1252, 1185, 1024 cm–1. 1H NMR (400 MHz, CDCl3): δ =
9.90 (d, J = 1.9 Hz, 1 H), 7.29 (d, J = 8.7 Hz, 2 H), 6.84 (d, J =
8.7 Hz, 2 H), 6.71 (s, 1 H), 5.62 (d, J = 11.3 Hz, 1 H), 4.38–4.30
(m, 2 H), 3.78 (s, 3 H), 3.76–3.69 (m, 1 H), 1.91 (sept., J = 7.0 Hz,
1 H), 1.37 (t, J = 7.1 Hz, 3 H), 1.16 (d, J = 7.0 Hz, 3 H), 0.92 (d,
J = 7.0 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 203.7,
164.38, 164.34, 159.3, 130.0, 127.6, 120.4, 114.4, 61.9, 57.8, 55.2,
39.8, 28.0, 21.7, 16.8, 14.0 ppm. HRMS (FAB+): calcd. for
C18H24NO6 [M + H]+ 350.1604; found 350.1606. Diastereomeric
ratio: Ͼ99:1; enantiomeric excess was determined by HPLC (Chi-
ralcel OD-H; iPrOH/hexanes, 5:95; flow rate = 0.5 mL/min; λ =
254 nm): tR = 14.3 (major), 19.0 (minor) min. 1d (recovery acetate):
Spectroscopic data were in agreement with racemic substrate 1d.
Yield: 42% (29.1 mg); enantiomeric excess was determined by
HPLC (Chiralcel OD-H; iPrOH/hexanes, 5:95; flow rate = 1.0 mL/
min; λ = 254 nm): tR = 12.8 (major), 14.4 (minor) min.
General Procedure for the Organocatalytic Kinetic Resolution with
Aldehydes: To a solution of racemic nitroallylic acetate rac-1a–n
(0.2 mmol) and aldehyde (0.3 mmol) in toluene (0.4 mL), was
added organocatalyst 2b (1.0 m in toluene, 0.005 mmol, 5 μL) at
0 °C. The reaction mixture was stirred at 0 °C for the indicated
time (the reaction was monitored at ca. 50% conversion by using
1
TLC or by H NMR analysis of the crude mixture). The reaction
mixture was subject directly to flash column chromatography on
silica gel (ethyl acetate/hexanes, 1:5) to afford the desired products.
The unreactive substrate was recovered. The data of the products
3a, 4a–g, 4i, 4k, 4n, and 4p were reported in our previous communi-
cation.[14]
(4S,5R)-Ethyl 5-Formyl-6-methyl-3-nitro-4-(4-methylphenyl)hept-2-
(Z)-enoate (3b): According to the general procedure, the resolution
of rac-1b (0.2 mmol, 61.4 mg) with isovaleraldehyde (0.3 mmol,
32 μL) in toluene (0.4 mL) and 2b (1.0 m in toluene, 0.005 mmol,
5 μL) at 0 °C for 15 h. Yield: 32% (21.3 mg) at 46% conversion.
(4S,5R)-Ethyl 5-Formyl-4-(2-bromophenyl)-6-methyl-3-nitrohept-2-
(Z)-enoate (3e): According to the general procedure, the resolution
IR (CH Cl ): ν = 2958, 2923, 1719, 1650, 1535, 1459, 1365, 1298,
˜
2
2
358
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 353–365

Kinetic Resolution of Activated Nitroallylic Acetates
of rac-1e (0.2 mmol, 74.4 mg) with isovaleraldehyde (0.3 mmol,
32 μL) in toluene (0.4 mL) and 2b (1.0 m in toluene, 0.01 mmol,
10 μL) at 0 °C for 24 h. Yield: 20% (16.0 mg) at 24% conversion.
iPrOH/hexanes, 5:95; flow rate = 0.5 mL/min; λ = 254 nm): tR =
18.4 (minor), 23.1 (major) min.
(4S,5R)-Ethyl
5-Formyl-4-(4-chlorophenyl)-6-methyl-3-nitrohept-
IR (CH Cl ): ν = 2966, 2898, 1769, 1641, 1536, 1455, 1338, 1201,
˜
2
2
1
2(Z)-enoate (3h): According to the general procedure, the resolu-
tion of rac-1h (0.2 mmol, 65.4 mg) with isovaleraldehyde
(0.3 mmol, 32 μL) in toluene (0.4 mL) and 2b (1.0 m in toluene,
0.005 mmol, 5 μL) at 0 °C for 15 h. Yield: 36% (25.5 mg) at 48%
1019 cm–1. H NMR (400 MHz, CDCl3): δ = 9.95 (d, J = 2.1 Hz,
1 H), 7.58 (dd, J = 0.8, 7.1 Hz, 1 H), 7.39 (d, J = 7.9 Hz, 1 H),
7.36–7.30 (m, 1 H), 7.20–7.12 (m, 1 H), 6.78 (s, 1 H), 5.90 (d, J =
11.5 Hz, 1 H), 4.40–4.26 (m, 2 H), 3.56–3.48 (m, 1 H), 1.88 (sept.,
J = 7.0 Hz, 1 H), 1.36 (t, J = 7.0 Hz, 3 H), 1.10 (d, J = 7.0 Hz, 3
H), 1.05 (d, J = 7.0 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 203.6, 163.8, 160.9, 133.7, 133.0, 130.0, 129.7, 128.1, 126.4,
122.7, 62.2, 58.0, 41.5, 28.0, 21.6, 16.8, 14.1 ppm. HRMS (FAB+):
calcd. for C17H21NBrO5 [M + H]+ 398.0603; found 398.0610. Dia-
stereomeric ratio: Ͼ99:1; enantiomeric excess was determined by
HPLC (Chiralpak AD-H; iPrOH/hexanes, 5:95; flow rate =
0.5 mL/min; λ = 254 nm): tR = 12.7 (minor), 14.5 (major) min. 1e
(recovery acetate): Spectroscopic data were in agreement with race-
mic substrate of 1e. Yield: 65% (48.2 mg); enantiomeric excess was
determined by HPLC (Chiralpak AD-H; iPrOH/hexanes, 5:95;
flow rate = 0.5 mL/min; λ = 254 nm): tR = 15.4 (minor), 17.3
(major) min.
conversion. IR (CH Cl ): ν = 2998, 2968, 1766, 1658, 1536, 1476,
˜
2
2
1372, 1256, 1185, 1054 cm–1. 1H NMR (400 MHz, CDCl3): δ =
9.88 (d, J = 1.3 Hz, 1 H), 7.35 (d, J = 8.4 Hz, 2 H), 7.29 (d, J =
8.5 Hz, 2 H), 6.80 (s, 1 H), 5.65 (d, J = 11.2 Hz, 1 H), 4.38–4.30
(m, 2 H), 3.77–3.72 (m, 1 H), 1.88 (sept., J = 7.0 Hz, 1 H), 1.37 (t,
J = 7.1 Hz, 3 H), 1.18 (d, J = 7.0 Hz, 3 H), 0.91 (d, J = 7.0 Hz, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 203.2, 164.2, 163.5,
134.6, 134.0, 130.3, 129.2, 121.4, 62.0, 57.6, 39.8, 28.0, 21.7, 16.8,
14.0 ppm. HRMS (FAB+): calcd. for C17H21NClO5 [M + H]+
354.1108; found 350.1100. 1h (recovery acetate): Spectroscopic data
were in agreement with racemic substrate 1h. Yield: 38% (24.9 mg);
enantiomeric excess was determined by HPLC (Chiralcel OD-H;
iPrOH/hexanes: 5:95; flow rate = 1.0 mL/min; λ = 254 nm): tR
=
7.3 (major), 8.4 (minor) min.
(4S,5R)-Ethyl 5-Formyl-4-(4-bromophenyl)-6-methyl-3-nitrohept-2-
(Z)-enoate (3f): According to the general procedure, the resolution
of rac-1f (0.2 mmol, 74.4 mg) with isovaleraldehyde (0.3 mmol,
32 μL) in toluene (0.4 mL) and 2b (1.0 m in toluene, 0.005 mmol,
5 μL) at 0 °C for 15 h. Yield: 36% (28.5 mg) at 49% conversion.
(4R,5R)-Ethyl 5-Formyl-4-(furan-2-yl)-6-methyl-3-nitrohept-2(Z)-
enoate (3k): According to the general procedure, the resolution of
rac-1k (0.2 mmol, 56.6 mg) with isovaleraldehyde (0.3 mmol,
32 μL) in toluene (0.4 mL) and 2b (1.0 m in toluene, 0.01 mmol,
10 μL) at 0 °C for 20 h. Yield: 18% (11.2 mg) at 24% conversion.
IR (CH Cl ): ν = 2978, 2908, 1742, 1638, 1525, 1465, 1342, 1267,
˜
2
2
1201, 1068 cm–1. 1H NMR (400 MHz, CDCl3): δ = 9.87 (d, J =
1.6 Hz, 1 H), 7.45 (d, J = 8.4 Hz, 2 H), 7.29 (d, J = 8.4 Hz, 2 H),
6.81 (s, 1 H), 5.64 (d, J = 11.2 Hz, 1 H), 4.40–4.30 (m, 2 H), 3.78–
3.72 (m, 1 H), 1.88 (sept., J = 7.0 Hz, 1 H), 1.37 (t, J = 7.1 Hz, 3
H), 1.19 (d, J = 7.0 Hz, 3 H), 0.89 (d, J = 7.0 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 203.1, 164.2, 163.4, 135.1, 132.2,
130.6, 122.2, 121.5, 62.0, 57.5, 39.8, 28.0, 21.7, 16.8, 14.0 ppm.
HRMS (FAB+): calcd. for C17H21NBrO5 [M + H]+ 398.0603; found
398.0608. Diastereomeric ratio: Ͼ99:1; enantiomeric excess was de-
termined by HPLC (Chiralcel OD-H; iPrOH/hexanes, 5:95; flow
rate = 1.0 mL/min; λ = 254 nm): tR = 8.0 (major), 10.3 (minor) min.
1f (recovery acetate): Spectroscopic data were in agreement with
racemic substrate 1f. Yield: 39% (28.9 mg); enantiomeric excess was
determined by HPLC (Chiralcel OD-H; iPrOH/hexanes, 5:95; flow
IR (CH Cl ): ν = 2966, 2925, 1723, 1657, 1539, 1465, 1343, 1207,
˜
2
2
1
1015 cm–1. H NMR (400 MHz, CDCl3): δ = 9.82 (d, J = 1.7 Hz,
1 H), 7.35–7.32 (m, 1 H), 6.85 (s, 1 H), 6.34–6.28 (m, 2 H), 5.77
(d, J = 10.9 Hz, 1 H), 4.38–4.30 (m, 2 H), 3.75–3.68 (m, 1 H), 1.98
(sept., J = 7.0 Hz, 1 H), 1.37 (t, J = 7.1 Hz, 3 H), 1.18 (d, J =
7.0 Hz, 3 H), 0.96 (d, J = 7.0 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 202.8, 164.0, 161.4, 149.6, 142.4, 121.5, 110.7, 108.9,
62.0, 57.9, 35.2, 28.5, 21.4, 17.3, 14.0 ppm. HRMS (FAB+): calcd.
for C15H20NO6 [M
+
H]+ 310.1291; found 310.1287. Dia-
stereomeric ratio: Ͼ99:1; enantiomeric excess was determined by
HPLC (Chiralcel OD-H; iPrOH/hexanes, 5:95; flow rate = 1.0 mL/
min; λ = 254 nm): tR = 11.6 (major),16.7 (minor) min. 1k (recovery
acetate): Spectroscopic data were in agreement with racemic sub-
strate of 1k. Yield: 68% (38.4 mg); enantiomeric excess was deter-
mined by HPLC (Chiralcel OD-H; iPrOH/hexanes, 10:90; flow rate
= 0.5 mL/min; λ = 254 nm): tR = 18.8 (minor), 21.0 (minor) min.
rate
= 1.0 mL/min; λ = 254 nm): tR = 10.2 (major), 12.7
(minor) min.
(4S,5R)-Ethyl 5-Formyl-4-(3-chlorophenyl)-6-methyl-3-nitrohept-2- (4S,5R)-Ethyl
5-Formyl-6-methyl-3-nitro-4-(1-phenyl-1H-indol-3-
(Z)-enoate (3g): According to the general procedure, the resolution
of rac-1g (0.2 mmol, 65.4 mg) with isovaleraldehyde (0.3 mmol,
32 μL) in toluene (0.4 mL) and 2b (1.0 m in toluene, 0.01 mmol,
10 μL) at 0 °C for 12 h. Yield: 35% (25.0 mg) at 47% conversion.
yl)hept-2(Z)-enoate (3l): According to the general procedure, the
resolution of rac-1l (0.2 mmol, 81.6 mg) with isovaleraldehyde
(0.3 mmol, 32 μL) in toluene (0.4 mL) and 2b (1.0 m in toluene,
0.01 mmol, 10 μL) at 0 °C for 24 h. Yield: 16% (14.0 mg) at 20%
IR (CH Cl ): ν = 2958, 2898, 1715, 1646, 1535, 1338, 1199,
conversion. IR (CH Cl ): ν = 2964, 2929, 1719, 1652, 1592, 1539,
˜
2 2
˜
2
2
1
1019 cm–1. H NMR (400 MHz, CDCl3): δ = 9.88 (d, J = 1.6 Hz, 1500, 1453, 1368, 1202, 1021 cm–1. 1H NMR (400 MHz, CDCl3):
1 H), 7.41 (s, 1 H), 7.32–7.30 (m, 1 H), 7.29–7.25 (m, 2 H), 6.83 (s, δ = 9.94 (d, J = 2.5 Hz, 1 H), 7.77 (dd, J = 1.4, 5.8 Hz, 1 H), 7.54–
1 H), 5.66 (d, J = 11.2 Hz, 1 H), 4.40–4.32 (m, 2 H), 3.80–3.74 (m, 7.48 (m, 3 H), 7.47–7.42 (m, 2 H), 7.40–7.36 (m, 1 H), 7.25 (s, 1
1 H), 1.90 (sept., J = 7.0 Hz, 1 H), 1.38 (t, J = 7.0 Hz, 3 H), 1.19 H), 7.24–7.18 (m, 2 H), 6.80 (s, 1 H), 6.15 (d, J = 11.2 Hz, 1 H),
(d, J = 7.1 Hz, 3 H), 0.92 (d, J = 7.1 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 203.1, 164.2, 163.2, 138.1, 134.8, 130.2, H), 1.39 (t, J = 7.1 Hz, 3 H), 1.15 (d, J = 6.9 Hz, 3 H), 0.98 (d, J
4.44–4.36 (m, 2 H), 3.80–3.72 (m, 1 H), 2.12 (sept., J = 7.1 Hz, 1
129.2, 128.3, 127.0, 121.7, 62.1, 57.5, 40.0, 28.1, 21.7, 16.9,
14.0 ppm. HRMS (FAB+): calcd. for C17H21ClNO5 [M + H]+
354.1108; found 354.1105. Diastereomeric ratio: Ͼ99:1; enantio-
meric excess was determined by HPLC (Chiralpak IA; iPrOH/hex-
anes, 2:98; flow rate = 0.5 mL/min; λ = 254 nm): tR = 10.5 (minor),
= 6.9 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 204.0,
164.5, 163.4, 139.2, 135.7, 129.7, 128.7, 127.3, 126.8, 124.4, 123.0,
120.7, 119.2, 111.3, 110.7, 62.0, 60.0, 32.4, 28.5, 21.9, 17.3,
14.1 ppm. HRMS (EI): calcd. for C25H26N2O5 [M]+ 434.1842;
found 434.1847. Diastereomeric ratio: Ͼ99:1; enantiomeric excess
11.8 (major) min. 1g (recovery acetate): Spectroscopic data were in was determined by HPLC (Chiralcel OD-H; iPrOH/hexanes: 5:95;
agreement with racemic substrate 1g. Yield: 41% (26.7 mg); enan- flow rate = 0.5 mL/min; λ = 254 nm): tR = 12.9 (major) min (er Ͼ
tiomeric excess was determined by HPLC (Chiralpak AD-H; 99:1, minor peak not observed). 1l (recovery acetate): Spectroscopic
Eur. J. Org. Chem. 2012, 353–365
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
359

K. Chen et al.
FULL PAPER
data were in agreement with racemic substrate of 1l. Yield: 70%
(57.0 mg); enantiomeric excess was determined by HPLC (Chi-
ralpak AD-H; iPrOH/hexanes, 5:95; flow rate = 0.5 mL/min; λ =
254 nm): tR = 23.2 (minor), 26.4 (major) min.
ratio: 98:2; enantiomeric excess was determined by HPLC (Chi-
ralcel OD-H; iPrOH/hexanes, 5:95; flow rate = 0.5 mL/min; λ =
254 nm): tR = 15.6 (major), 17.1 (minor) min. 1f (recovery acetate):
Spectroscopic data were in agreement with racemic substrate of 1f.
Yield: 28% (205 mg). The enantiomeric excess was determined by
HPLC (Chiralcel OD-H; iPrOH/hexanes, 5:95; flow rate = 1.0 mL/
min; λ = 254 nm): tR = 9.3 (major), 11.3 (minor) min.
(4S,5R)-Ethyl 5-Formyl-3-nitro-4-(4-methoxyphenyl)oct-2(Z)-enoate
(4h): According to the general procedure, the resolution of rac-1d
(0.2 mmol, 64.6 mg) with valeraldehyde (0.3 mmol, 32 μL) in tolu-
ene (0.4 mL) and 2b (1.0 m in toluene, 0.005 mmol, 5 μL) at 0 °C
(4S,5R)-Ethyl 5-Formyl-3-nitro-4-(3-chlorophenyl)oct-2(Z)-enoate
(4m): According to the general procedure, the resolution of rac-1g
(0.2 mmol, 65.4 mg) with valeraldehyde (0.3 mmol, 32 μL) in tolu-
for 12 h. Yield: 40% (27.8 mg) at 52% conversion. IR (CH Cl ): ν
˜
2
2
= 2988, 2924, 1726, 1654, 1554, 1504, 1486, 1367, 1262, 1189,
1
1082 cm–1. H NMR (400 MHz, CDCl3): δ = 9.76 (d, J = 2.5 Hz, ene (0.4 mL) and 2b (1.0 m in toluene, 0.005 mmol, 5 μL) at 0 °C
1 H), 7.27 (dd, J = 2.9, 6.8 Hz, 2 H), 6.85 (dd, J = 3.0, 6.8 Hz, 2
H), 6.73 (s, 1 H), 5.38 (d, J = 11.3 Hz, 1 H), 4.36–4.28 (m, 2 H),
for 12 h. Yield: 52% (36.5 mg) at 66% conversion. IR (CH Cl ): ν
˜
2 2
= 2960, 2919, 1711, 1638, 1528, 1452, 1379, 1219, 1050 cm–1. 1H
3.78 (s, 3 H), 3.70–3.66 (m, 1 H), 1.62–1.52 (m, 2 H), 1.36 (t, J = NMR (400 MHz, CDCl3): δ = 9.75 (s, 1 H), 7.38 (s, 1 H), 7.28–
7.0 Hz, 3 H), 1.28–1.22 (m, 2 H), 0.84 (t, J = 7.3 Hz, 3 H) ppm. 7.25 (m, 3 H), 6.85 (s, 1 H), 5.43 (d, J = 11.2 Hz, 1 H), 4.38–4.30
13C NMR (100 MHz, CDCl3): δ = 203.2, 164.2, 163.9, 159.3, 130.0, (m, 2 H), 3.69–3.74 (m, 1 H), 1.62–1.54 (m, 2 H), 1.35 (t, J =
127.1, 120.7, 114.3, 61.9, 55.2, 52.7, 41.5, 30.4, 19.7, 14.06,
14.01 ppm. HRMS (FAB+): calcd. for C18H24NO6 [M + H]+
350.1604; found 350.1605. Diastereomeric ratio: 99:1; enantiomeric
excess was determined by HPLC (Chiralcel OD-H; iPrOH/hexanes,
5:95; flow rate = 0.5 mL/min; λ = 254 nm): tR = 15.3 (major), 17.3
(minor) min. 1d (recovery acetate): Spectroscopic data were in
agreement with racemic substrate of 1d. Yield: 38% (24.3 mg). The
enantiomeric excess was determined by HPLC (Chiralcel OD-H;
7.4 Hz, 3 H), 1.28–1.24 (m, 2 H), 0.86 (t, J = 7.2 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 202.6, 164.1, 162.7, 137.7, 134.8,
130.2, 129.2, 128.4, 127.0, 122.0, 62.2, 52.3, 41.7, 30.5, 19.5, 14.06,
14.01 ppm. HRMS (FAB+): calcd. for C17H21NClO5 [M + H]+
354.1108; found 350.1115. Diastereomeric ratio: 99:1; enantiomeric
excess was determined by HPLC (Chiralpak AD-H; iPrOH/hex-
anes, 5:95; flow rate = 0.5 mL/min; λ = 254 nm): tR = 10.0 (minor),
10.6 (major) min. 1g (recovery acetate): Spectroscopic data were in
agreement with racemic substrate of 1g. Yield: 30% (19.4 mg). The
enantiomeric excess was determined by HPLC (Chiralpak AD-H;
iPrOH/hexanes, 5:95; flow rate = 1.0 mL/min; λ = 254 nm): tR
=
13.1 (major), 14.6 (minor) min.
iPrOH/hexanes, 5:95; flow rate = 1.0 mL/min; λ = 254 nm): tR
18.7 (minor), 23.8 (major) min.
=
(4S,5R)-Ethyl 5-Formyl-3-nitro-4-(2-bromophenyl)oct-2(Z)-enoate
(4j): According to the general procedure, the resolution of rac-1e
(0.2 mmol, 74.4 mg) with valeraldehyde (0.3 mmol, 32 μL) in tolu-
ene (0.4 mL) and 2b (1.0 m in toluene, 0.005 mmol, 5 μL) at 0 °C
(4S,5R)-Ethyl 5-Formyl-3-nitro-4-(4-chlorophenyl)hept-2(Z)-enoate
(4o): According to the general procedure, the resolution of rac-
1h (0.2 mmol, 65.4 mg) with butyraldehyde (0.3 mmol, 27 μL) in
toluene (0.4 mL) and 2b (1.0 m in toluene, 0.005 mmol, 5 μL) at
for 15 h. Yield: 25% (20.0 mg) at 34% conversion. IR (CH Cl ): ν
˜
2
2
= 2860, 2919, 2866, 1753, 1666, 1559, 1469, 1378, 1346, 1212, 1079,
1019 cm–1. H NMR (400 MHz, CDCl3): δ = 9.78 (d, J = 1.9 Hz, 0 °C for 12 h. Yield: 49% (33.1 mg) at 61% conversion. IR
1
1 H), 7.57 (d, J = 7.9 Hz, 1 H), 7.40 (d, J = 7.8 Hz, 1 H), 7.34 (m,
1 H), 7.17 (m, 1 H), 6.83 (s, 1 H), 5.46 (d, J = 11.4 Hz, 1 H), 4.35–
4.26 (m, 2 H), 3.62–3.56 (m, 1 H), 1.72–1.66 (m, 1 H), 1.48–1.42
(m, 2 H), 1.40–1.28 (m, 4 H), 0.87 (t, J = 7.2 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 202.9, 163.7, 160.5, 133.7, 133.0,
130.0, 129.7, 128.0, 126.5, 123.0, 62.2, 53.3, 43.3, 30.2, 20.1, 14.0,
13.9 ppm. HRMS (FAB+): calcd. for C17H21NBrO5 [M + H]+
398.0603; found 398.0604. Diastereomeric ratio: Ͼ99:1; enantio-
meric excess was determined by HPLC (Chiralpak AD-H; iPrOH/
(CH Cl ): ν = 2991, 2964, 1709, 1628, 1553, 1524, 1406, 1357, 1256,
˜
2 2
1182, 1018 cm–1. 1H NMR (400 MHz, CDCl3): δ = 9.74 (d, J =
1.9 Hz, 1 H), 7.36–7.28 (m, 4 H), 6.83 (s, 1 H), 5.46 (d, J = 11.3 Hz,
1 H), 4.38–4.29 (m, 2 H), 3.72–3.66 (m, 1 H), 1.78–1.70 (m, 1 H),
1.62–1.54 (m, 1 H), 1.36 (t, J = 7.1 Hz, 3 H), 0.90 (t, J = 7.4 Hz,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 202.5, 164.1, 163.0,
134.2, 134.0, 130.3, 129.1, 121.7, 62.1, 53.5, 40.9, 21.0, 14.0,
10.3 ppm. HRMS (FAB+): calcd. for C16H19NClO5 [M + H]+
340.0952; found 340.0951. Diastereomeric ratio: 99:1; enantiomeric
hexanes, 5:95; flow rate = 0.5 mL/min; λ = 254 nm): tR = 12.4 excess was determined by HPLC (Chiralcel OD-H, iPrOH/hexanes,
(minor), 13.5 (major) min. 1e (recovery acetate): Spectroscopic data
were in agreement with racemic substrate of 1e. Yield: 58%
(43.0 mg). The enantiomeric excess was determined by HPLC (Chi-
ralpak AD-H; iPrOH/hexanes, 5:95; flow rate = 0.5 mL/min; λ =
254 nm); tR = 15.3 (minor), 17.1 (major) min.
2:98; flow rate = 0.5 mL/min; λ = 254 nm): tR = 21.2 (major), 23.9
(minor) min. 1h (recovery acetate): Spectroscopic data were in
agreement with racemic substrate of 1h. Yield: 30% (19.4 mg). The
enantiomeric excess was determined by HPLC (Chiralpak AD-H;
iPrOH/hexanes, 5:95; flow rate = 0.5 mL/min; λ = 254 nm): tR
=
7.1 (major), 8.6 (minor) min.
(4S,5R)-Ethyl 5-Formyl-3-nitro-4-(4-bromophenyl)oct-2(Z)-enoate
(4l): According to the general procedure, the resolution of rac-1f
(2 mmol, 744 mg) with butyraldehyde (3 mmol, 270 μL) in toluene
(4S,5R)-Ethyl 5-Formyl-4-(naphthalen-2-yl)-6-methyl-3-nitrohept-
2(Z)-enoate (4q): According to the general procedure, the resolu-
(4 mL) and 2b (1.0 m in toluene, 0.05 mmol, 50 μL) at 0 °C for 10 h. tion of rac-1i (0.2 mmol, 68.6 mg) with butyraldehyde (0.3 mmol,
Yield: 48% (366 mg) at 59% conversion. IR (CH Cl ): ν = 2964,
27 μL) in toluene (0.4 mL) and 2b (1.0 m in toluene, 0.005 mmol,
5 μL) at 0 °C for 12 h. Yield: 51% (37.5 mg) at 62% conversion.
˜
2
2
2929, 2872, 1723, 1656, 1539, 1489, 1368, 1336, 1202, 1070,
1
1010 cm–1. H NMR (400 MHz, CDCl3): δ = 9.75 (d, J = 2.2 Hz, IR (CH Cl ): ν = 2986, 2970, 1773, 1665, 1559, 1492, 1348, 1246,
˜
2
2
1
1 H), 7.45 (dd, J = 1.8, 4.8 Hz, 2 H), 7.27 (dd, J = 1.8, 4.9 Hz, 2
H), 6.83 (s, 1 H), 5.42 (d, J = 11.3 Hz, 1 H), 4.38–4.28 (m, 2 H),
3.73–3.65 (m, 1 H), 1.62–1.54 (m, 2 H), 1.36 (t, J = 7.2 Hz, 3 H),
0.85 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
202.7, 164.1, 163.0, 134.7, 132.2, 130.7, 122.2, 121.8, 62.2, 52.3,
41.6, 30.4, 19.6, 14.09, 14.04 ppm. HRMS (FAB+): calcd. for
C16H17NBrO5 [M – H]– 382.0297; found 382.0290. Diastereomeric
1148, 1032 cm–1. H NMR (400 MHz, CDCl3): δ = 9.82 (s, 1 H),
7.85 (s, 1 H), 7.81 (d, J = 8.8 Hz, 3 H), 7.50–7.46 (m, 3 H), 6.82
(s, 1 H), 5.65 (d, J = 11.3 Hz, 1 H), 4.40–4.32 (m, 2 H), 3.88–3.84
(m, 1 H), 1.78–1.74 (m, 1 H), 1.69–1.62 (m, 1 H), 1.37 (t, J =
7.1 Hz, 3 H), 0.92 (d, J = 7.5 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 202.9, 164.2, 163.5, 133.4, 132.95, 132.90, 128.8, 128.4,
127.9, 127.5, 126.45, 126.43, 126.2, 121.4, 62.0, 53.7, 41.7, 21.1,
360
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 353–365

Kinetic Resolution of Activated Nitroallylic Acetates
14.0, 10.4 ppm. HRMS (FAB+): calcd. for C20H21NO5 [M]+
355.1420; found 355.1418. Diastereomeric ratio: 99:1; enantiomeric
excess was determined by HPLC (Chiralpak AD-H; iPrOH/hex-
anes, 5:95; flow rate = 0.5 mL/min; λ = 254 nm): tR = 14.1 (minor),
15.2 (major) min. 1i (recovery acetate): Spectroscopic data were in
agreement with racemic substrate 1i. Yield: 34% (23.2 mg). The
enantiomeric excess was determined by HPLC (Chiralcel OD-H;
excess was determined by HPLC (Chiralpak AD-H; iPrOH/hex-
anes, 5:95; flow rate = 0.5 mL/min; λ = 254 nm): tR = 18.5 (major),
21.5 (minor) min.
(R,Z)-Ethyl 4-(3-Methoxyphenyl)-3-nitro-4-[(S)-2-oxocyclohexyl]-
but-2-enoate (5c): According to the general procedure, the resolu-
tion of rac-1c (0.15 mmol, 48.5 mg) with cyclohexanone
(0.45 mmol, 46.6 μL) and acetic acid (0.3 mmol, 17 μL) in MTBE
(0.05 mL) and 14c (0.03 mmol, 8.5 mg) at 0 °C for 1 d. Yield: 35%
iPrOH/hexanes: 5:95; flow rate = 0.5 mL/min; λ = 254 nm): tR
=
26.2 (major), 31.5 (minor) min.
(19 mg) at 41% conversion. IR (CH Cl ): ν = 2936, 2859, 1723,
˜
2
2
General Procedure for the Organocatalytic Kinetic Resolution with
Cyclohexanone: To solution of cyclic ketone (0.45 mmol),
1713, 1653, 1533, 1489, 1371, 1262, 1200 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 7.25–7.19 (m, 1 H), 7.02–6.97 (m, 2 H),
6.83 (s, 1 H), 6.82–6.77 (m, 1 H), 5.21 (d, J = 10.8 Hz, 1 H), 4.37–
4.24 (m, 2 H), 3.78 (s, 3 H), 3.71 (td, J = 11.8, 5.2 Hz, 1 H), 2.50–
2.33 (m, 2 H), 2.17–2.07 (m, 1 H), 2.05–1.95 (m, 1 H), 1.86–1.76
(m, 1 H), 1.75–1.56 (m, 2 H), 1.34 (t, J = 7.1 Hz, 3 H), 1.33–1.28
(m, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 212.0, 164.6,
164.5, 159.9, 138.9, 129.8, 121.4, 120.6, 115.0, 113.0, 61.7, 55.2,
52.8, 43.7, 42.3, 33.9, 28.5, 25.2, 14.1 ppm. HRMS (ESI): calcd. for
a
organocatalyst 14c (0.03 mmol, 8.5 mg), and acetic acid (0.3 mmol,
17 μL) in MTBE (0.05 mL), was added racemic nitroallylic acetate
rac-1a–h, o, p (0.15 mmol) at 0 °C. The reaction mixture was stirred
at 0 °C for the necessary time, as indicated in Table 3 (the reaction
1
was monitored at ca. 50% conversion by using TLC or H NMR
analysis of the crude mixtures). The reaction mixture was subject
directly to flash column chromatography on silica gel (ethyl acetate/
hexanes, 1:15) to afford the pure product as a yellow oil. The unre-
active substrate was also recovered.
C19H23NO6Na [M
+
Na]+ 384.1423; found 384.1428. Dia-
stereomeric ratio: Ͼ99:1; enantiomeric excess was determined by
HPLC (Chiralcel AD-H; iPrOH/hexanes, 2:98; flow rate = 0.5 mL/
min; λ = 254 nm): tR = 26.6 (major), 28.2 (minor) min. Recovery
nitroallylic acetate 1c: spectroscopic data are in agreement with ra-
cemic substrate 1c. Yield: 38% (18 mg). The enantiomeric excess
was determined by HPLC (Chiralpak AD-H; iPrOH/hexanes, 3:97;
flow rate = 1.0 mL/min; λ = 254 nm): tR = 15.5 (major), 17.1
(minor) min.
(R,Z)-Ethyl 3-Nitro-4-[(S)-2-oxocyclohexyl]-4-phenylbut-2-enoate
(5a): According to the general procedure, the resolution of rac-1a
(0.15 mmol, 44.0 mg) with cyclohexanone (0.45 mmol, 46.6 μL)
and acetic acid (0.3 mmol, 17 μL) in MTBE (0.05 mL) and 14c
(0.03 mmol, 8.5 mg) at 0 °C for 1 d. Yield: 37% (18 mg) at 43%
conversion. IR (CH Cl ): ν = 2940, 2862, 1723, 1714, 1537, 1450,
˜
2
2
1
1338, 1206 cm–1. H NMR (400 MHz, CDCl3): δ = 7.45–7.39 (m,
2 H), 7.33–7.21 (m, 3 H), 6.84 (s, 1 H), 5.23 (d, J = 10.9 Hz, 1 H),
4.37–4.24 (m, 2 H), 3.73 (td, J = 11.6, 5.1 Hz, 1 H), 2.50–2.35 (m,
2 H), 2.16–2.06 (m, 1 H), 2.03–1.93 (m, 1 H), 1.85–1.75 (m, 1 H),
(R,Z)-Ethyl 4-(4-Methoxyphenyl)-3-nitro-4-[(S)-2-oxocyclohexyl]-
but-2-enoate (5d): According to the general procedure, the resolu-
tion of rac-1d (0.15 mmol, 48.5 mg) with cyclohexanone
1.75–1.56 (m, 2 H), 1.34 (t, J = 7.1 Hz, 3 H), 1.30–1.23 (m, 1 (0.45 mmol, 46.6 μL) and acetic acid (0.3 mmol, 17 μL) in MTBE
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 212.0, 164.8, 164.5,
137.4, 129.1, 128.9, 127.8, 120.5, 61.7, 52.7, 43.7, 42.3, 33.9, 28.5,
25.2, 14.1 ppm. HRMS (ESI): calcd. for C18H21NO5Na
[M + Na]+ 354.1317; found 354.1312. Diastereomeric ratio: Ͼ99:1;
enantiomeric excess was determined by HPLC (Chiralcel AD-H;
(0.05 mL) and 14c (0.03 mmol, 8.5 mg) at 0 °C for 1 d. Yield: 37%
(20 mg) at 43% conversion. IR (CH Cl ): ν = 2938, 2861, 1723,
˜
2
2
1717, 1656, 1537, 1463, 1322, 1205 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 7.34 (d, J = 8.7 Hz, 2 H), 6.83 (d, J = 8.7 Hz, 2 H),
6.80 (s, 1 H), 5.19 (d, J = 10.9 Hz, 1 H), 4.35–4.25 (m, 2 H), 3.77
(s, 3 H), 3.68 (td, J = 11.7, 5.2 Hz, 1 H), 2.49–2.32 (m, 2 H), 2.16–
2.06 (m, 1 H), 2.05–1.95 (m, 1 H), 1.86–1.76 (m, 1 H), 1.75–1.55
(m, 2 H), 1.34 (t, J = 7.1 Hz, 3 H), 1.31–1.21 (m, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 211.9, 165.1, 164.6, 159.1, 130.2,
129.3, 120.0, 114.3, 61.6, 55.2, 52.8, 42.9, 42.3, 33.8, 28.5, 25.2,
14.1 ppm. HRMS (ESI): calcd. for C19H23NO6Na [M + Na]+
384.1423; found 384.1430. Diastereomeric ratio: Ͼ99:1; enantio-
meric excess was determined by HPLC (Chiralcel AD-H; iPrOH/
hexanes, 5:95; flow rate = 0.5 mL/min; λ = 254 nm): tR = 20.2
(major), 22.7 (minor) min. Recovery nitroallylic acetate 1d: spectro-
scopic data were in agreement with racemic substrate 1d. Yield:
40% (19 mg). The enantiomeric excess was determined by HPLC
(Chiralpak AD-H; iPrOH/hexanes, 10:90; flow rate = 1.0 mL/min;
λ = 254 nm): tR = 12.3 (major), 14.3 (minor) min.
iPrOH/hexanes, 5:95; flow rate = 0.5 mL/min; λ = 254 nm): tR
=
12.8 (major), 14.8 (minor) min. Recovery nitroallylic acetate 1a:
spectroscopic data were in agreement with racemic substrate 1a.
Yield: 36% (15.8 mg). The enantiomeric excess was determined by
HPLC (Chiralpak AD-H; iPrOH/hexanes, 5:95; flow rate =
0.5 mL/min; λ = 254 nm): tR = 22.6 (major), 25.9 (minor) min.
(R,Z)-Ethyl 3-Nitro-4-[(S)-2-oxocyclohexyl]-4-(p-tolyl)but-2-enoate
(5b): According to the general procedure, the resolution of rac-1b
(0.15 mmol, 46.1 mg) with cyclohexanone (0.45 mmol, 46.6 μL)
and acetic acid (0.3 mmol, 17 μL) in MTBE (0.05 mL) and 14c
(0.03 mmol, 8.5 mg) at 0 °C for 1 d. Yield: 37% (19 mg) at 43%
conversion. IR (CH Cl ): ν = 2926, 2855, 1724, 1717, 1533, 1449,
˜
2
2
1335, 1203 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.30 (d, J =
8.1 Hz, 2 H), 7.11 (d, J = 8.1 Hz, 2 H), 6.81 (s, 1 H), 5.21 (d, J =
10.8 Hz, 1 H), 4.37–4.23 (m, 2 H), 3.70 (td, J = 11.7, 5.0 Hz, 1 H),
2.49–2.35 (m, 2 H), 2.31 (s, 3 H), 2.16–2.06 (m, 1 H), 2.03–1.93 (m,
1 H), 1.85–1.75 (m, 1 H), 1.74–1.57 (m, 2 H), 1.34 (t, J = 7.1 Hz,
(R,Z)-Ethyl 4-(2-Bromophenyl)-3-nitro-4-[(S)-2-oxocyclohexyl]but-
2-enoate (5e): According to the general procedure, the resolution
of rac-1e (0.15 mmol, 55.8 mg) with cyclohexanone (0.45 mmol,
3 H), 1.32–1.25 (m, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 46.6 μL) and acetic acid (0.3 mmol, 17 μL) in MTBE (0.05 mL)
212.1, 165.0, 164.6, 137.6, 134.3, 129.6, 128.9, 120.2, 61.6, 52.7,
43.3, 42.3, 33.9, 28.5, 25.2, 21.0, 14.1 ppm. HRMS (ESI): calcd. for
and 14c (0.03 mmol, 8.5 mg) at 0 °C for 1 d. Yield: 37% (23 mg) at
43% conversion. IR (CH Cl ): ν = 2940, 2865, 1727, 1716, 1659,
˜
2
2
C19H23NO5Na [M
+
Na]+ 368.1474; found 368.1482. Dia-
1537, 1469, 1336, 1206 cm–1. 1H NMR (400 MHz, CDCl3): δ =
7.58 (dd, J = 8.0, 1.1 Hz, 1 H), 7.48 (d, J = 7.9, 1.4 Hz, 1 H), 7.32–
7.25 (m, 1 H), 7.16–7.09 (m, 1 H), 6.94 (s, 1 H), 5.49 (d, J =
10.9 Hz, 1 H), 4.36–4.23 (m, 2 H), 3.69–3.60 (m, 1 H), 2.54–2.33
(m, 2 H), 2.13–2.01 (m, 1 H), 1.89–1.67 (m, 3 H), 1.64–1.51 (m, 2
H), 1.33 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
stereomeric ratio: Ͼ99:1; enantiomeric excess was determined by
HPLC (Chiralcel OD-H; iPrOH/hexanes, 10:90; flow rate =
1.0 mL/min; λ = 254 nm): tR = 6.1 (major), 13.0 (minor) min. Re-
covery nitroallylic acetate 1b: spectroscopic data were in agreement
with racemic substrate 1b. Yield: 43% (20 mg). The enantiomeric
Eur. J. Org. Chem. 2012, 353–365
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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361

K. Chen et al.
36% conversion. IR (CH Cl ): ν = 2943, 2862, 1722, 1716, 1658,
FULL PAPER
δ = 210.7, 164.0, 162.0, 136.5, 133.7, 129.6, 129.2, 128.2, 126.2,
˜
2
2
122.0, 61.9, 53.6, 43.5, 41.9, 32.5, 28.0, 24.9, 14.1 ppm. HRMS 1535, 1492, 1345, 1208 cm–1. 1H NMR (400 MHz, CDCl3): δ =
(ESI): calcd. for C18H20NO5NaBr [M + Na]+ 432.0423; found
432.0433. Diastereomeric ratio: Ͼ99:1; enantiomeric excess was de-
termined by HPLC (Chiralcel AD-H; iPrOH/hexanes, 5:95; flow
7.39 (d, J = 8.5 Hz, 2 H), 7.28 (d, J = 8.5 Hz, 2 H), 6.86 (s, 1 H),
5.21 (d, J = 10.9 Hz, 1 H), 4.36–4.24 (m, 2 H), 3.67 (td, J = 11.7,
5.2 Hz, 1 H), 2.47–2.35 (m, 2 H), 2.17–2.07 (m, 1 H), 2.00–1.91 (m,
1 H), 1.86–1.76 (m, 1 H), 1.74–1.61 (m, 2 H), 1.34 (t, J = 7.1 Hz,
3 H), 1.32–1.22 (m, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
rate
= 0.5 mL/min; λ = 254 nm): tR =19.1 (major), 20.8
(minor) min. Recovery nitroallylic acetate 1e: spectroscopic data
were in agreement with racemic substrate 1e. Yield: 27% (15 mg). 211.6, 164.5, 164.4, 136.0, 133.7, 130.6, 129.1, 120.8, 61.8, 52.6,
The enantiomeric excess was determined by HPLC (Chiralpak AD-
H; iPrOH/hexanes, 5:95; flow rate = 1.0 mL/min; λ = 254 nm): tR
= 17.6 (major), 20.3 (minor) min.
43.1, 42.2, 33.8, 28.4, 25.1, 14.1 ppm. HRMS (ESI): calcd. for
C18H20NO5NaCl [M + Na]+ 388.0928; found 388.0936. Dia-
stereomeric ratio: Ͼ99:1; enantiomeric excess was determined by
HPLC (Chiralcel AD-H; iPrOH/hexanes, 5:95; flow rate = 0.5 mL/
min; λ = 254 nm): tR = 14.8 (major), 16.0 (minor) min. Recovery
nitroallylic acetate 1h: spectroscopic data were in agreement with
racemic substrate 1h. Yield: 30% (15 mg). The enantiomeric excess
was determined by HPLC (Chiralpak AD-H; iPrOH/hexanes, 1:99;
flow rate = 0.7 mL/min; λ = 254 nm): tR = 72.0 (major), 78.6
(minor) min.
(R,Z)-Ethyl 4-(4-Bromophenyl)-3-nitro-4-[(S)-2-oxocyclohexyl]but-
2-enoate (5f): According to the general procedure, the resolution of
rac-1f (0.15 mmol, 55.8 mg) with cyclohexanone (0.45 mmol,
46.6 μL) and acetic acid (0.3 mmol, 17 μL) in MTBE (0.05 mL)
and 14c (0.03 mmol, 8.5 mg) at 0 °C for 1 d. Yield: 26% (16 mg) at
34% conversion. IR (CH Cl ): ν = 2941, 2864, 1723, 1716, 1658,
˜
2
2
1537, 1488, 1345, 1207 cm–1. 1H NMR (400 MHz, CDCl3): δ =
7.43 (d, J = 8.4 Hz, 2 H), 7.33 (d, J = 8.4 Hz, 2 H), 6.86 (s, 1 H),
5.20 (d, J = 10.8 Hz, 1 H), 4.36–4.24 (m, 2 H), 3.66 (td, J = 11.8,
5.1 Hz, 1 H), 2.48–2.35 (m, 2 H), 2.17–2.05 (m, 1 H), 2.01–1.91 (m,
1 H), 1.87–1.76 (m, 1 H), 1.74–1.60 (m, 2 H), 1.34 (t, J = 7.1 Hz,
3 H), 1.31–1.21 (m, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
211.6, 164.4, 164.3, 136.5, 132.0, 131.0, 121.9, 120.9, 61.8, 52.6,
43.2, 42.2, 33.8, 28.4, 25.1, 14.1 ppm. HRMS (ESI): calcd. for
C18H20NO5NaBr [M + Na]+ 432.0423; found 432.0431. Dia-
stereomeric ratio: Ͼ99:1; enantiomeric excess was determined by
HPLC (Chiralcel AD-H; iPrOH/hexanes, 5:95; flow rate = 0.5 mL/
min; λ = 254 nm): tR = 14.9 (major), 16.1 (minor) min. Recovery
nitroallylic acetate 1f: spectroscopic data were in agreement with
racemic substrate 1f. Yield: 23% (13 mg). The enantiomeric excess
was determined by HPLC (Chiralpak OD-H; iPrOH/hexanes: 5:95;
flow rate = 0.5 mL/min; λ = 220 nm): tR = 20.8 (minor), 24.6
(major) min.
(R,Z)-Ethyl 4-(2-Methoxyphenyl)-3-nitro-4-[(S)-2-oxocyclohexyl]-
but-2-enoate (5o): According to the general procedure, the resolu-
tion of rac-1o (0.15 mmol, 48.5 mg) with cyclohexanone
(0.45 mmol, 46.6 μL) and acetic acid (0.3 mmol, 17 μL) in MTBE
(0.05 mL) and 14c (0.03 mmol, 8.5 mg) at 0 °C for 1 d. Yield: 40%
(22 mg) at 44% conversion. IR (CH Cl ): ν = 2939, 2861, 1725,
˜
2
2
1714, 1654, 1534, 1492, 1335, 1200 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 7.35 (dd, J = 7.5, 0.9 Hz, 1 H), 7.28–7.19 (m, 1 H),
6.96–6.88 (m, 1 H), 6.83 (d, J = 8.2 Hz, 1 H), 6.71 (s, 1 H), 5.43
(d, J = 11.0 Hz, 1 H), 4.34–4.19 (m, 2 H), 3.76 (td, J = 11.3, 4.9 Hz,
1 H), 3.72 (s, 3 H), 2.55–2.41 (m, 2 H), 2.14–2.00 (m, 1 H), 1.91–
1.76 (m, 2 H), 1.76–1.56 (m, 2 H), 1.43–1.32 (m, 1 H), 1.31 (t, J =
7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 212.0, 164.2,
163.9, 157.9, 130.2, 128.9, 124.9, 120.8, 120.5, 110.9, 61.4, 55.0,
51.3, 42.2, 39.1, 33.2, 28.3, 24.9, 14.1 ppm. HRMS (APCI): calcd.
for C19H24NO6 [M
+
H]+ 362.1604; found 362.1607. Dia-
stereomeric ratio: Ͼ99:1; enantiomeric excess was determined by
HPLC (Chiralcel OD-H; iPrOH/hexanes, 15:85; flow rate =
0.7 mL/min; λ = 220 nm): tR = 10.4 (major), 15.8 (minor) min. Re-
covery nitroallylic acetate 1o: spectroscopic data were in agreement
with racemic substrate 1o. Yield: 35% (17 mg). The enantiomeric
excess was determined by HPLC (Chiralpak OD-H; iPrOH/hex-
anes, 3:97; flow rate = 0.5 mL/min; λ = 220 nm): tR = 30.7 (minor),
33.5 (major) min.
(R,Z)-Ethyl 4-(3-Chlorophenyl)-3-nitro-4-[(S)-2-oxocyclohexyl]but-
2-enoate (5g): According to the general procedure, the resolution
of rac-1g (0.15 mmol, 49.2 mg) with cyclohexanone (0.45 mmol,
46.6 μL) and acetic acid (0.3 mmol, 17 μL) in MTBE (0.05 mL)
and 14c (0.03 mmol, 8.5 mg) at 0 °C for 1 d. Yield: 22% (12 mg) at
31% conversion. IR (CH Cl ): ν = 2938, 2860, 1722, 1715, 1660,
˜
2
2
1537, 1476, 1336, 1208 cm–1. 1H NMR (400 MHz, CDCl3): δ =
7.47–7.44 (m, 1 H), 7.35–7.30 (m, 1 H), 7.26–7.22 (m, 2 H), 6.89
(s, 1 H), 5.21 (d, J = 10.8 Hz, 1 H), 4.36–4.26 (m, 2 H), 3.69 (td, J
= 11.9, 5.1 Hz, 1 H), 2.47–2.35 (m, 2 H), 2.16–2.06 (m, 1 H), 2.01–
1.92 (m, 1 H), 1.87–1.77 (m, 1 H), 1.76–1.62 (m, 2 H), 1.35 (t, J =
7.1 Hz, 3 H), 1.33–1.27 (m, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 211.6, 164.4, 164.0, 139.5, 134.7, 130.1, 129.3, 128.1,
127.4, 121.1, 61.9, 52.6, 43.4, 42.2, 33.9, 28.4, 25.1, 14.1 ppm.
HRMS (ESI): calcd. for C18H20NO5NaCl [M + Na]+ 388.0928;
found 388.0939. Diastereomeric ratio: Ͼ99:1; enantiomeric excess
was determined by HPLC (Chiralcel AD-H; iPrOH/hexanes, 5:95;
flow rate = 0.5 mL/min; λ = 254 nm): tR = 12.5 (major), 13.8
(minor) min. Recovery nitroallylic acetate 1g: spectroscopic data
were in agreement with racemic substrate 1g. Yield: 29% (14 mg).
The enantiomeric excess was determined by HPLC (Chiralpak AD-
H; iPrOH/hexanes, 5:95; flow rate = 0.5 mL/min; λ = 220 nm): tR
= 23.5 (major), 31.2 (minor) min.
(R,Z)-Ethyl 4-(3-Bromophenyl)-3-nitro-4-[(S)-2-oxocyclohexyl]but-
2-enoate (5p): According to the general procedure, the resolution
of rac-1p (0.15 mmol, 55.8 mg) with cyclohexanone (0.45 mmol,
46.6 μL) and acetic acid (0.3 mmol, 17 μL) in MTBE (0.05 mL)
and 14c (0.03 mmol, 8.5 mg) at 0 °C for 1 d. Yield: 20% (12 mg) at
29% conversion. IR (CH Cl ): ν = 2940, 2863, 1722, 1715, 1655,
˜
2
2
1536, 1474, 1336, 1207 cm–1. 1H NMR (400 MHz, CDCl3): δ =
7.63–7.58 (m, 1 H), 7.42–7.35 (m, 2 H), 7.18 (t, J = 7.9 Hz, 1 H),
6.89 (s, 1 H), 5.19 (d, J = 10.8 Hz, 1 H), 4.36–4.26 (m, 2 H), 3.68
(td, J = 12.0, 5.2 Hz, 1 H), 2.48–2.35 (m, 2 H), 2.18–2.05 (m, 1 H),
2.02–1.92 (m, 1 H), 1.89–1.76 (m, 1 H), 1.75–1.62 (m, 2 H), 1.35
(t, J = 7.1 Hz, 3 H), 1.32–1.27 (m, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 211.6, 164.4, 164.0, 139.8, 132.2, 131.0, 130.4, 127.9,
122.9, 121.1, 61.9, 52.6, 43.4, 42.2, 33.9, 28.4, 25.1, 14.1 ppm.
HRMS (ESI): calcd. for C18H20NO5NaBr [M + Na]+ 432.0423;
found 432.0435. Diastereomeric ratio: Ͼ99:1; enantiomeric excess
(R,Z)-Ethyl 4-(4-Chlorophenyl)-3-nitro-4-[(S)-2-oxocyclohexyl]but- was determined by HPLC (Chiralcel AD-H; iPrOH/hexanes, 5:95;
2-enoate (5h): According to the general procedure, the resolution flow rate = 1.0 mL/min; λ = 254 nm): tR = 6.4 (major), 7.0
of rac-1h (0.15 mmol, 49.2 mg) with cyclohexanone (0.45 mmol, (minor) min. Recovery nitroallylic acetate 1p: spectroscopic data
46.6 μL) and acetic acid (0.3 mmol, 17 μL) in MTBE (0.05 mL)
and 14c (0.03 mmol, 8.5 mg) at 0 °C for 1 d. Yield: 28% (15 mg) at
were in agreement with racemic substrate 1p. Yield: 25% (14 mg).
The enantiomeric excess was determined by HPLC (Chiralpak OD-
362
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 353–365

Kinetic Resolution of Activated Nitroallylic Acetates
H; iPrOH/hexanes, 5:95; flow rate = 0.5 mL/min; λ = 220 nm): tR
= 24.3 (minor), 28.2 (major) min.
1.11 (s, 3 H), 1.10 (s, 3 H), 0.98 (s, 3 H), 0.97 (d, J = 7.0 Hz, 3 H),
0.71 (d, J = 7.0 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 177.8,
170.1, 167.6, 135.3, 128.9, 128.5, 128.2, 91.1, 90.9, 85.6, 64.7, 61.2,
54.7, 54.3, 50.9, 43.6, 32.4, 30.5, 29.0, 27.3, 21.8, 16.6, 15.5, 13.8,
9.6. HRMS (FAB+): calcd. for C27H38NO8 [M + H]+ 504.2597;
found 504.2602 (1H and 13C NMR analyses of the title product
represents a 75:25 diastereomeric mixture and here we assigned the
major diastereomer). Crystal data for 8 at 296(2) K. C27H37NO8;
M = 503.58; monoclinic; P2l; a = 10.2212(4) Å, b = 12.8077(5) Å,
c = 20.7401(9) Å; α = 20.7401(9)°, β = 90.00°, γ = 90.00°; V =
2715.09(19) Å3; F(000) = 388; λ(Mo-Kα) = 0.71073 Å; Z = 4; D =
1.232 g/cm3; 4731 reflections, 0 restraints, 325 parameters, R =
0.0824; Rw = 0.1440 for all data.
(4S,5R)-Ethyl
5-(Hydroxymethyl)-6-methyl-3-nitro-4-phenylhept-
anoate (6): To a stirred solution of 3a (0.2 mmol, 63.8 mg) in
MeOH (4.0 mL) at 0 °C, was added NaBH4 (0.3 mmol, 11.4 mg).
The reaction was stirred for 15 min at 0 °C and quenched with sat.
NH4Cl (3 mL) and water (3 mL). The organic layer was extracted
with CH2Cl2 (3ϫ15 mL) and the combined organic layer was
washed with brine, dried with MgSO4, filtered and the solvent was
removed under reduced pressure. The obtained crude product was
purified by flash column chromatography on silica gel (ethyl acet-
ate/hexanes, 1:4) to afford the pure product 6 as a colorless liquid
in 70% (45.2 mg) yield. IR (CH Cl ): ν = 3568, 2957, 2921, 1734,
˜
2
2
1648, 1553, 1453, 1372, 1248, 1170, 1028 cm–1. 1H NMR
(E)-Ethyl 2-Hydroxy-3-nitro-4-phenylbut-3-enoate (9): To a reco-
(400 MHz, CDCl3): δ = 7.34–7.27 (m, 3 H), 7.08–7.02 (m, 2 H), vered optically enriched nitroallylic acetate (+)-1a (94%ee; 80 mg,
5.62–5.58 (m, 1 H), 4.16–4.08 (m, 2 H), 3.95 (dd, J = 1.8, 8.9 Hz,
1 H), 3.77 (dd, J = 4.4, 6.8 Hz, 1 H), 3.70 (dd, J = 1.8, 8.9 Hz, 1
H), 3.00 (dd, J = 2.1, 15.3 Hz, 1 H), 2.92 (dd, J = 3.8, 5.9 Hz, 1
H), 2.11 (br. s, 1 H), 1.96–1.88 (m, 1 H), 1.58–1.50 (m, 1 H), 1.20
0.27 mmol) in MeOH (1.0 mL), was added Sm(OTf)3 (196 mg,
0.32 mmol) at ambient temperature. The reaction mixture was
stirred until the complete consumption of the starting substrate
was observed (reaction monitored by TLC analysis). The reaction
(t, J = 7.2 Hz, 3 H), 0.95 (d, J = 7.0 Hz, 3 H), 0.66 (d, J = 7.0 Hz, mixture was quenched with water (2 mL) and extracted with
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.4, 136.2, 128.8,
128.6, 126.8, 86.1, 61.0, 51.1, 38.8, 46.5, 32.7, 30.8, 27.3, 22.0,
14.0 ppm. HRMS (FAB+): calcd. for C17H25NO5Na [M + Na]+
346.1630; found 346.1635.
CH2Cl2 (2ϫ10 mL). The layers were separated and the combined
organic layer was washed with brine, dried with MgSO4, filtered,
and evaporated under reduced pressure. The crude product was
purified by flash column chromatography on silica gel (ethyl acet-
ate/hexanes, 5:1) to afford alcohol 9 (48 mg, 70% yield) as a color-
less oil. Spectroscopic data (IR, H1 and C13 NMR, and HRMS)
were in agreement with the published data. The enantiomeric excess
was determined by HPLC (Chiralcel OD-H; iPrOH/hexanes, 10:90;
flow rate = 1.0 mL/min; λ = 254 nm): tR = 11.1 (major), 8.9
(minor) min.
(4S,5R)-Ethyl 5-(Hydroxymethyl)-3-nitro-4-phenylheptanoate (7):
Reduction of 4b (0.2 mmol, 61.0 mg) in MeOH (4.0 mL) at 0 °C
was performed by adding NaBH4 (0.3 mmol, 11.0 mg) according
to the method described above. Yield: 60% (38.0 mg). IR (CH2Cl2):
ν = 3558, 2977, 2931, 1724, 1656, 1556, 1455, 1370, 1246, 1179,
˜
1
1029 cm–1. H NMR (400 MHz, CDCl3): δ = 7.35–7.27 (m, 3 H),
7.14–7.10 (m, 2 H), 5.56–5.50 (m, 1 H), 4.14–4.02 (m, 2 H), 3.76
(R,E)-1-(Ethoxycarbonyl)-2-nitro-3-phenylallyl
4-Nitrobenzoate
(dd, J = 3.3, 7.6 Hz, 1 H), 3.60 (t, J = 7.8 Hz, 1 H), 3.36 (t, J = (10): To a solution of alcohol 9 (0.18 mmol, 45 mg) in CH2Cl2
9.0 Hz, 1 H), 3.00 and 2.95 (ABq, J = 11.0 Hz, 1 H), 2.65–2.60 (m,
1 H), 1.76–1.66 (m, 1 H), 1.64–1.54 (m, 1 H), 1.19 (t, J = 7.0 Hz,
3 H), 1.04–0.94 (m, 1 H), 0.85 (d, J = 7.8 Hz, 3 H) ppm. 13C NMR
(10 mL), was added p-nitrobenzoic acid (0.22 mmol, 36 mg) and a
catalytic amount of DMAP in the presence of DCC (0.23 mmol,
48 mg). The reaction was stirred for 12 h at ambient temperature
(100 MHz, CDCl3): δ = 169.8, 135.6, 129.1, 128.8, 128.7, 128.7, and quenched with water (10 mL). The layers were separated and
127.9, 85.3, 62.5, 61.2, 49.9, 43.3, 35.2, 20.5, 13.9, 11.9 ppm.
HRMS (FAB+): calcd. for C16H23NO5 [M + H]+ 310.1654; found
310.1654 (1H and 13C NMR analyses of the title product represents
a 80:20 diastereomeric mixture and here we assigned the major
product).
the aqueous layer was extracted with CH2Cl2 (2ϫ8 mL). The com-
bined organic layer was washed with brine, dried with MgSO4, fil-
tered, and the solvent was removed under reduced pressure. The
product was purified by flash column chromatography on silica gel
(ethyl acetate/hexanes, 1:20) to give 10 as a yellow solid (28 mg,
40% yield); m.p 156–158 °C. IR (CH Cl ): ν = 1767, 1734, 1653,
˜
2
2
(1S,4R)-(2R,3S)-6-Ethoxy-2-isopropyl-4-nitro-6-oxo-3-phenyl-
hexyl-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carb-
oxylate (8): To a solution of the primary alcohol 6 (0.1 mmol,
32.3 mg) and DMAP (0.2 mmol, 24.4 mg) in CH2Cl2 (3 mL), was
added (–)-camphanic acid chloride (0.2 mmol, 43.2 mg) at 0 °C. Af-
ter stirring for 1 h at ambient temperature, the reaction mixture
was quenched with water (5 mL) and the mixture was extracted
with CH2Cl2 (2ϫ10 mL). The combined organic layer was washed
with 10% aq. HCl solution, saturated aq. NaHCO3, brine, and
dried with Na2SO4. Filtration and evaporation in vacuo followed
by flash column chromatography (silica gel; hexanes/EtOAc, 4:1)
provided camphanyl ester 8 (35.0 mg, 70%) as a white solid. The
product was recrystallized from EtOAc/hexanes in a sealed vessel
to yield a colorless crystal that was suitable for single-crystal X-ray
1605, 1531, 1340, 1262, 1222, 1096, 1037 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 8.51 (s, 1 H), 8.29 (d, J = 8.7 Hz, 2 H),
8.23 (d, J = 8.7 Hz, 2 H), 7.52 (s, 5 H), 6.83 (s, 1 H), 4.30–4.24 (m,
2 H), 1.25 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 165.4, 163.1, 151.0, 144.3, 141.1, 133.9, 131.6, 131.3, 130.2,
129.7, 129.4, 123.6, 66.6, 63.0, 13.9 ppm. X-ray data for 10 at
200(2) K. C19H16N2O8; M = 400.34; monoclinic; P21/a; a =
15.6370(4) Å, b = 6.7130(2) Å, c = 18.4780(5) Å. α = 90°, β =
101.8600(10)°, γ = 90°; V = 1898.25(9) Å3; F(000) = 832; λ(Mo-Kα)
= 0.71073 Å; Z = 4; D = 1.401 Mg/m3; 10653 reflections collected,
3348 (Rint = 0.0554) independent reflections, 0 restraints, 262 pa-
rameters, R indices (all data), R1 = 0.0764, wR2 = 0.1564.
(4S,5R)-Ethyl 5-(Hydroxymethyl)-3-nitro-4-phenylheptanoate (12):
analysis. IR (CH Cl ): ν = 2964, 2929, 1790, 1734, 1648, 1553, To a solution of (S)-citronellal (11; 1.0 mmol, 0.18 mL) and race-
˜
2
2
1453, 1379, 1265, 1166, 1102 cm–1. 1H NMR (400 MHz, CDCl3):
mic nitroallylic acetate 1a (1.0 mmol, 0.29 g) in toluene (2 mL), was
δ = 7.34–7.25 (m, 3 H), 7.08–7.02 (m, 2 H), 5.24–5.18 (m, 1 H), added organocatalyst 2b (1.0 m in toluene, 0.025 mmol, 25 μL) at
4.46 (dd, J = 1.6, 10.4 Hz, 1 H), 4.25 (dd, J = 4.0, 8.0 Hz, 1 H),
4.14–4.06 (m, 1 H), 4.02–3.96 (m, 1 H), 3.66 (dd, J = 4.6, 6.4 Hz,
1 H), 3.00–2.92 (m, 1 H), 2.42–2.36 (m, 1 H), 2.16–2.08 (m, 2 H),
1.96–1.92 (m, 1 H), 1.68–1.60 (m, 3 H), 1.19 (t, J = 7.0 Hz, 3 H),
0 °C. The reaction mixture was stirred at 0 °C for 12 h and was
monitored at ca. 50% conversion by using TLC or crude 1H analy-
sis. After evaporation of toluene under reduced pressure, the reac-
tion mixture was subject directly to flash column chromatography
Eur. J. Org. Chem. 2012, 353–365
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
363

K. Chen et al.
FULL PAPER
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as a pale-yellowish liquid (133 mg, 34% yield) and the remaining
substrate (+)-1a was recovered in 38% yield (112 mg). IR (CH2Cl2):
ν = 2987, 2941, 1742, 1686, 1576, 1458, 1376, 1341, 1296, 1166,
˜
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1
1028 cm–1. H NMR (400 MHz, CDCl3): δ = 9.88 (s, 1 H), 7.38–
7.34 (m, 2 H), 7.33–7.27 (m, 3 H), 6.75 (s, 1 H), 5.69 (d, J =
11.4 Hz, 1 H), 5.02–4.97 (m, 1 H), 4.38–4.30 (m, 2 H), 3.89 (d, J
= 11.4 Hz, 1 H), 2.08–2.02 (m, 2 H), 1.74–1.70 (m, 1 H), 1.64 (s, 3
H), 1.63–1.59 (m, 1 H), 1.58 (s, 3 H), 1.50–1.44 (m, 1 H), 1.37 (t,
J = 7.2 Hz, 3 H), 0.92 (d, J = 6.9 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 203.6, 164.3, 164.0, 135.7, 132.2, 129.0,
128.9, 128.0, 123.5, 121.0, 61.9, 55.7, 40.3, 35.8, 32.3, 25.7, 25.6,
17.6, 14.8, 14.0 ppm. HRMS (FAB+): calcd. for C22H30NO5 [M +
H]+ 388.2124; found 388.2122 (1H and 13C NMR analyses of the
title product indicate a single diastereomer). Recovery nitroallylic
acetate 1a: spectroscopic data were in agreement with racemic sub-
strate 1a. The enantiomeric excess was determined by HPLC (Chi-
ralpak AD-H; iPrOH/hexanes, 5:95; flow rate = 0.5 mL/min; λ =
254 nm): tR = 20.5 (minor), 23.5 (major) min.
(S)-Ethyl 4-[(1R,2S,3R,6S)-2-Hydroxy-3-(2-hydroxypropan-2-yl)-6-
methylcyclohexyl]-3-nitro-4-phenyl-but-2(Z)-enoate (13): To a solu-
tion of 12 (0.2 mmol, 77.4 mg) in toluene (0.5 mL), was added
InBr3 (0.3 mmol, 106 mg) at 0 °C. After stirring at ambient tem-
perature for 1 h, the reaction was quenched with H2O (2 mL) and
extracted with CH2Cl2 (2ϫ5 mL). The combined organic layer was
washed with brine, dried with MgSO4, filtered, and the solvent was
evaporated under reduced pressure. The crude product was purified
by flash column chromatography on silica gel (ethyl acetate/hex-
anes, 1:4) to provide the desired product 13 as a colorless liquid
[5]
(50 mg, 62% yield). IR (CH Cl ): ν = 3658, 3224, 2987, 2941, 1625,
˜
2
2
1576, 1458, 1376, 1341, 1266, 1028 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 7.32–7.24 (m, 5 H), 6.72 (s, 1 H), 5.29 (d, J = 9.6 Hz,
1 H), 4.42–4.36 (m, 3 H), 3.83 (br. s, 1 H), 3.29 (br. s, 1 H), 2.75–
2.70 (m, 1 H), 1.94–1.88 (m, 1 H), 1.78–1.72 (m, 1 H), 1.70–1.66
(s, 1 H), 1.62–1.54 (m, 2 H), 1.50–1.44 (m, 1 H), 1.39 (t, J = 5.7 Hz,
3 H), 1.32 (s, 3 H), 1.22 (s, 3 H), 0.90 (d, J = 10.9 Hz, 3 H). 13C
NMR (100 MHz, CDCl3): δ = 165.9, 165.4, 135.2, 129.2, 128.9,
128.0, 121.0, 72.8, 70.4, 62.7, 49.8, 45.0, 44.5, 33.1, 28.7, 28.5, 27.5,
15.2, 14.5, 14.0. HRMS (FAB+): calcd. for C22H32NO6 [M + H]+
406.2230; found 406.2225.
[6]
Supporting Information (see footnote on the first page of this arti-
cle): Characterization data, copies of the HPLC chromatograms,
1H and 13C NMR spectra of all new products, and X-ray crystallo-
graphic data for 8 and 10.
[7]
[8]
Acknowledgments
We thank the National Science Council of the Republic of China
(NSC 99-2113-M-003-002-MY3 and NSC 99-2119-M-003-001-
MY2) and National Taiwan Normal University (100-D-6 and 99- [9]
D) for financial support of this work. Our gratitude extends to the
National Center for High-Performance Computing for providing
us with computer time and facilities.
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Kinetic Resolution of Activated Nitroallylic Acetates
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from The Cambridge Crystallographic Data Centre via
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Received: August 8, 2011
Published Online: November 11, 2011
Eur. J. Org. Chem. 2012, 353–365
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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