Asymmetric Synthesis of Functionalized Tetrahydronaphthalenes via an Organocatalytic Nitroalkane-Michael/Henry Domino Reaction

Article abstract of DOI:10.1002/adsc.201300039

An organocatalytic nitroalkane-Michael/Henry reaction sequence to functionalized 1,2,3,4-tetrahydronaphthalen-1-ols is described. Starting from 2-(nitromethyl)benzaldehyde and nitroalkenes a bifunctional quinine-based squaramide organocatalyst is used to afford the title compounds in moderate to very good yields (25-84%), high diastereomeric ratios (dr>95:5) after crystallization and good to excellent enantioselectivities of 63-99% ee. Starting from γ-nitro aldehydes and ketones secondary and tertiary cyclohexanols bearing four stereogenic centers can also be prepared with this Michael/Henry domino reaction. Copyright

Full text of DOI:10.1002/adsc.201300039

FULL PAPERS
DOI: 10.1002/adsc.201300039
Asymmetric Synthesis of Functionalized Tetrahydronaphthalenes
via an Organocatalytic Nitroalkane-Michael/Henry Domino
Reaction
Dieter Enders,a,* Robert Hahn,a and Iuliana Atodireseia
a
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
Fax : (+49)-241-809-2127; e-mail: enders@rwth-aachen.de
Received: January 23, 2013; Revised: March 15, 2013; Published online: April 8, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300039.
Abstract: An organocatalytic nitroalkane-Michael/ to excellent enantioselectivities of 63–99% ee. Start-
Henry reaction sequence to functionalized 1,2,3,4- ing from g-nitro aldehydes and ketones secondary
tetrahydronaphthalen-1-ols is described. Starting and tertiary cyclohexanols bearing four stereogenic
from 2-(nitromethyl)benzaldehyde and nitroalkenes centers can also be prepared with this Michael/
a bifunctional quinine-based squaramide organocata- Henry domino reaction.
lyst is used to afford the title compounds in moder-
ate to very good yields (25–84%), high diastereo- Keywords: cyclohexanes; domino reactions; organo-
meric ratios (dr>95:5) after crystallization and good catalysis; squaramides; tetrahydronaphthalenes
Introduction
thalen-1-ols via a nitroalkane-Michael/Henry reaction
sequence using a hydrogen-bonding squaramide orga-
The trio of general concepts of asymmetric catalysis, nocatalyst.
namely biocatalysis, metal catalysis and organocataly-
sis,[1] constitutes a basic platform of modern synthetic
chemistry. Especially the latter field, the catalysis with Results and Discussion
small organic molecules, has grown with enormous
speed since about the turn of the millennium. Among To access the title tetrahydronaphthalenes we envis-
the various subfields of organocatalysis, domino or aged the reaction of 2-(nitromethyl)benzaldehyde
cascade reactions[2] have been intensively investigated (3a) with b-nitrostyrenes 4 based on a related
during the past few years, which open up efficient nitroalk
direct entries to complex molecules from simple pre- developed in our group.[7] The cascade starts with
cursors in a single one-pot operation. a nucleophilic attack of the g-nitro aldehyde to the
The 1,2,3,4-tetrahydronaphthalene moiety is pres- nitroalkene, which becomes the nitronate donor for
ACHTUNGTRENaNUNG ne-Michael/aldol reaction sequence, that was
AHCTUNGTRENNUNG
ent as a characteristic structural feature in the class of a subsequent ring closure to the cyclohexane through
second generation rodenticides, like difenacoum, bro- an intramolecular Henry reaction.
difacoum and flocoumafen,[3a,b] in MT2 melatonin re-
Firstly, a shorter and more efficient route to alde-
ceptor antagonists,[3c] and can also inhibit the growth hyde 3a as compared to the known procedure has
of human tumor cells lines.[3d] Therefore diastereo- been worked out (Scheme 1).[7] The benzaldehyde 2
and enantioselective syntheses of these compounds was obtained by reduction of the nitrile group of com-
and of cyclohexanes in general are of great inter- mercially available 2-(bromomethyl)benzonitrile (1)
est.[4,5] In recent years several different strategies for with DIBAL-H and followed by acidic hydrolysis.[8a]
the catalytic asymmetric synthesis of polysubstituted Subsequently treatment with silver nitrite[8b] at 08C
cyclohexanes bearing contiguous stereocenters have yielded the desired g-nitroaldehyde 3a.[9]
been developed, including covalent enamine/iminium
activation modes as well as hydrogen-bonding con- (nitromethyl)benz
cepts.[6]
with different hydrogen-bonding thiourea and squara-
We
investigated
the
reaction
of
2-
AHCTUNGTRENNUNG
We now would like to report the asymmetric syn- mide organocatalysts. All of them are reported to fa-
thesis of polyfunctionalized 1,2,3,4-tetrahydronaph- cilitate the conversion of a-acidic nitro compounds to
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Adv. Synth. Catal. 2013, 355, 1126 – 1136

Asymmetric Synthesis of Functionalized Tetrahydronaphthalenes
Table 1. Catalyst screening for the nitroalkane-Michael/
Henry sequence of 2-(nitromethyl)benzaldehyde (3a) and
nitrostyrene (4a) yielding diastereomeric mixtures of the
1,2,3,4-tetrahydronaphthalen-1-ols 5.
Scheme 1. Improved two-step protocol for the synthesis of
2-(nitromethyl)benzaldehyde (3a).
various Michael-acceptors.[10] Due to their bifunction-
al character, the organocatalysts can activate both the
acceptor and the donor in which the nitro group can
serve as a directing moiety.
Nearly all tested catalysts A–H promoted the an-
ticipated domino reaction, which resulted in a mixture
of four diastereomers 5 with respect to the stereocen-
ters in the 1- and 4-positions. All have in common
their trans-relationship at the 2,3-positions. The orga-
nocatalyst A with its binaphthyl backbone gave
a yield of 43% with a low diastereoselectivity and
a modest enantiomeric excess of 46% of the major
diastereomer (Table 1, entry 1). After 5.5 days 83%
yield of 5 in 27% ee (Table 1, entry 2) could be ob-
tained with the norephedrine-derived catalyst B that
was recently developed in our group.[11] No satisfying
improvement was achieved after applying the qui-
nine-based catalyst C (49% yield, 59% ee) and its
pseudo-enantiomer D (61% yield, 13% ee) in the
domino reaction (Table 1, entries 3 and 4). Switching
from thiourea-based catalysts to the more efficient
hydrogen-bonding squaramides led to an overall im-
provement. With catalyst E an excellent enantioselec-
tivity with good diastereselectivity of the major
isomer was achieved in a short reaction time (Table 1,
entry 5). Compared to E, a decrease of enantioselec-
tivity (93% to 58%) was observed with the quinidine-
derived catalyst F (Table 1, entry 6). No conversion
was detected with catalyst G, probably because
a more basic moiety is needed than a hydrogen bond
directing group (Table 1, entry 7). The squaramide
catalyst H also gave a low enantioselectivity (Table 1,
entry 8).
Entry[a]
Cat.
t [d]
Yield [%][b]
5, dr[c]
ee [%][d]
1
2
3
4
5
6
7
8
A
B
C
D
E
F
9
5.5
6
43
83
49
61
59
72
0
1:1:6:3
1:2:15:7
n.d.[f]
46[e]
27
59
7
n.d.[f]
13[e]
93
0.5
0.5
21
1
1:2:22:3
1:1:40:3
–
58[e]
–
G
H
62
1:2:14:4
28[e]
[a]
Reactions were performed on
a 0.5 mmol scale at
À208C.
[b]
Combined yield of isolated product 5 as a mixture of dia-
stereomers after flash chromatography.
Determined by H NMR spectroscopy.
[c]
[d]
1
Determined by HPLC analysis on a chiral stationary
phase for the major (1R,2S,3R,4R)-5 diastereomer.
The opposite enantiomer of the major diastereomer was
obtained.
[e]
[f]
With the suitable catalyst E in hand, further screen-
ing of catalyst loading, solvent and temperature was
conducted (Table 2). The catalyst loading could be re-
duced to 5 mol% while still providing good results
Not determined.
(Table 2, entries 1–3). After testing different chlori- to be the best choice with excellent 94% ee. Common
nated solvents (Table 2, entry 4 and 5), CHCl3 proved solvents in organocatalytic reactions like toluene and
Adv. Synth. Catal. 2013, 355, 1126 – 1136
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Dieter Enders et al.
FULL PAPERS
Table 2. Screening for the optimized conditions including catalyst loading, solvent and temperature for the nitroalkane-
Michael/Henry reaction sequence.
Entry[a]
E [mol%]
Solvent
T [8C]
Time [h]
Yield [%][b]
5, dr[c]
ee [%][d]
1
2
3
4
5
6
7
8
9
10
5
1
5
5
5
5
5
5
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
CHCl3
CH2Cl2
toluene
Et2O
EtOAc
CHCl3
CHCl3
À20
À20
À20
À20
À20
À20
À20
À20
0
15
15
–
18
15
18
96
110
6
61
60
–
81
69
68
64
80
57
55
1:2:20:2
1:2:16:2
–
1:3:30:3
1:2:21:3
1:3:31:3
1:2:19:3
1:2:14:2
1:2:24:4
1:2:20:4
88
88
[e]
–
94 (>99)[f]
85
87
91
94
89
74
10
5
r.t.
6
[a]
The reactions were performed on a 0.5 mmol scale.
[b]
[c]
[d]
[e]
[f]
Combined yield of isolated product 5 as a mixture of diastereomers after flash chromatography.
1
Determined by H NMR spectroscopy.
Determined by HPLC analysis on a chiral stationary phase for the major (1R,2S,3R,4R)-5 diastereomer.
Stopped after four weeks.
After one recrystallization.
diethyl ether (Table 2, entry 6 and 7) could not com-
After the optimization of the conditions, we investi-
pete with chloroform. Ethyl acetate gave the same in- gated the scope of this reaction (Table 3). The reac-
duction but with lack of a good diastereoselectivity tions between 2-(nitromethyl)benzaldehyde (3a) and
(Table 2, entry 8). Increasing the temperature resulted various aromatic nitroalkenes 4 were examined. After
in a drop of enantioselectivity (Table 2, entries 9 and column chromatography, the diastereomeric mixtures
10).
were recrystallized and afforded the (1R,2S,3R,4R)-
1,2,3,4-tetrahydronaphthalen-1-ols 5a–o (dr>95:5).
Table 3. Scope of the nitroalkane-Michael/Henry reaction sequence to form the 1,2,3,4-tetrahydronaphthalen-1-ols 5a–o.
5[a]
R1
R2
Time [d]
Yield [%][b,c]
ee [%][d]
a
b
c
d
e
f
g
h
i
H
H
H
H
H
H
H
H
H
H
H
3-OMe
4-Br
5-F
H
Ph
1
5
3.5
4
5
7
1
1
5
3
17
6
6
4
70
81
40
71
48
50
78
84
51
68
62
41
35
45
42
94 (>99)
83
95
78
97
78 (91)
87 (97)
80 (82)
67 (87)
92
4-MeC6H4
4-MeOC6H4
3,4,5-(MeO)3C6H2
3-NO2C6H4
4-NO2C6H4
3-ClC6H4
4-ClC6H4
3,4-OCH2OC6H3
2-naphthyl
2-furyl
j
k
l[e]
m
n
o
64
Ph
Ph
Ph
Ph (Z)
63 (70)
81 (97)
77
6.5
86
[a]
[b]
[c]
[d]
[e]
The reactions were performed on a 0.5 mmol scale at À208C.
Combined yield of isolated product 5 as a mixture of diastereomers after flash chromatography.
After one recrystallization, dr>95:5 (major vs. the minor diastereomers).
Determined by HPLC analysis on a chiral stationary phase; value in bracket after one recrystallization.
The 4-epimer was obtained as major diastereomer.
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Asymmetric Synthesis of Functionalized Tetrahydronaphthalenes
Electron-donating substituents of the aromatic group
R2 like methyl or methoxy groups (Table 3, 5b–d)
generated the corresponding 1,2,3,4-tetrahydronaph-
thalen-1-ols in moderate to good yields (40–81%) and
very good enantioselectivities (78–95% ee). The posi-
tion of the substituents had a strong influence on the
stereoselectivity. Nitroolefins with a substituent in
meta-position delivered much better enantiomeric ex-
cesses than their para-counterparts (97% vs. 78% ee
for the nitro group and 87% vs. 80% ee for chloro
group, respectively, Table 3, 5e–h). Changing the
phenyl for a naphthyl group led to a good yield
Scheme 2. Asymmetric organocatalytic domino reaction to
form the secondary cyclohexanols 8 and 1-epi-8.
(68%) and a high enantioselectivity (92% ee) of 5j.[12] by the fact that the 1-epimeric cyclohexanol 8 has
As a representative for heterocyclic compounds, the each substituent in its thermodynamically more stable
furyl group was introduced, but only moderate results equatorial conformation. In the case of the tetrahy-
were obtained after a long reaction time (62% yield, dronaphthalen-1-ols, after the first bond is generated
64% ee, 5k). It should be mentioned that 1,2-disubsti- from the substrates 3 and 4, they form a conformation-
tuted nitroalkenes 4 cannot be used as Michael-ac- ally more rigid intermediate, whose configuration de-
ceptors in our protocol.
termines the final stereochemical outcome. The rela-
A few functionalized 2-(nitromethyl)benzaldehydes tively low combined yield can be explained with the
3l–n were also synthesized and applied in the cascade tendency of the g-nitro aldehyde 7 to undergo an in-
protocol (Table 3). They gave moderate yields (35– termolecular Henry reaction.
45%) and good enantioselectivities (63–81% ee). In-
By expanding the scope of our asymmetric organo-
terestingly, the major diastereomer was different as catalytic domino reaction to the aliphatic g-nitro
compared to the previous ones (Table 3, 5l). Propably ketone substrate 10 we were able to generate a terti-
due to the steric interference of the ortho-substituted ary alcohol function with the final Henry ring closure.
methoxy group 4-epi-5l was formed. To determine the The polysubstitued tertiary cyclohexanols 11a–d
influence of the nitroalkene configuration the synthe- (Table 4) were synthesized in moderate to good yields
sis of 5a was repeated using the corresponding (Z)- (47–68%), very good diastereomeric ratios (dr>95:5)
configured isomer (Table 3, 5o). Expecting a 3,4-cis- and with very good enantioselectivities (87–94% ee).
relationship as the stereochemical outcome, surpris- The relative configuration of the tertiary cyclohexa-
ingly the same product 5a was obtained, but in a mod- nols 11 could be assigned by NOE measurements
erate yield of 42% and almost the same enantioselec- (Figure 1, 11a). The absolute configuration of the tet-
tivity (86% ee). We assume that under the reaction
conditions a slow (E/Z) isomerization of nitrostyrene
can occur, which may explain the long reaction time
and lower yield.
Table 4. Scope of the nitroalkane-Michael/Henry reaction
sequence to form tertiary cyclohexanols 11a–d.
A further experiment was conducted on a gram
scale to prove the scalability of the model reaction for
compound 5a. As expected, the reaction proceeded in
the determined way with similar yield (1.36 g, 60%)
and enantioselectivity (85% ee). It is notable that the
amount of catalyst could be reduced to 1 mol% with
no drop of enantioselectivity.
In addition, we extended our domino protocol to
an aliphatic g-nitro aldehyde, which should undergo
the same cascade reaction like the aromatic counter-
part 3a (Scheme 2). To prove this, 4-nitrobutanal (7)
was reacted with (E)-nitrostyrene (4a) and furnished
the secondary cyclohexanols 8 and 1-epi-8.[13] Interest-
ingly, the absolute configuration of the secondary cy-
clohexanol 8 matches with the configuration of the
tetrahydronaphthalenes 5a–o, however, only a poor
yield (6%) and moderate enantioselectivity (64% ee)
was obtained. In contrast, the 1-epimer of 8 gave
a 25% yield with excellent enantioselectivity (97%
ee). This stereochemical outcome may be explained
11[a]
R1
t [d]
Yield [%][b,c]
ee [%][d]
a
b
c
Ph
1
5
3.5
4
61
77
68
47
89 (94)
89
91
4-ClC6H4
3-NO2C6H4
2-BrC6H4
d
87
[a]
The reactions were performed on a 0.5 mmol scale at
À208C.
[b]
[c]
[d]
Combined yield of isolated product 11 as a mixture of
diastereomers after flash chromatography.
After one recrystallization, dr>95:5 (major vs. the minor
diastereomers).
Determined by HPLC analysis on a chiral stationary
phase; value in brackets after one recrystallization.
Adv. Synth. Catal. 2013, 355, 1126 – 1136
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Dieter Enders et al.
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General Procedure for the Asymmetric Synthesis of
1,2,3,4-Tetrahydronaphthalen-1-ol Derivatives 5a–o
and the Cyclohexanols 1-epi-8 and 11a–d
In a glass vial equipped with a magnetic stirring bar the g-
nitro carbonyl compound 3, 7 or 10 (1.0 equiv,. 0.5 mmol),
nitroalkene 4 (1.1 equiv., 0.5–0.6 mmol) and catalyst E
(5 mol%) were dissolved in chloroform (1 mL). After stir-
ring at À208C for the appropriate time the crude solution
was directly purified by flash chromatography on silica gel
(n-hexane/ethyl acetate=8:1 to 2:1) to afford the com-
pounds 5a–o, 8 and 11a–d as colorless to yellow solids.
(1R,2S,3R,4R)-2,4-Dinitro-3-phenyl-1,2,3,4-tetrahydro-
naphthalen-1-ol (5a): Synthesized according to the general
procedure by using 2-(nitromethyl)benzaldehyde (3a)
(80 mg, 0.48 mmol) and (E)-(2-nitrovinyl)benzene (4a)
(85 mg, 0.57 mmol); colorless solid; yield: 106 mg (70%);
[a]25: +60.4 (c 0.28, CHCl3); 99% ee; Rf =0.71 (n-hexane/
ethDyl acetate=1:1); mp 1648C. IR (film): n=3511, 2044,
1996, 1613, 1552, 1493, 1451, 1367, 1291, 1230, 1118, 1048,
Figure 1. Determination of the relative and absolute config-
uration by NOE (11a) and X-ray crystal structure analysis
(5g).[14]
rahydronaphthalenes was determined by single crystal
X-ray analysis of compound 5g[14] (Figure 1).
1
911, 851, 775, 700 cmÀ1; H NMR (400 MHz, CD3OD): d=
4.67 (dd, J=10.3, 12.4 Hz, 1H, CHPh), 5.31 (d, J=3.6 Hz,
1H, CHOH), 5.62 (dd, J=3.6, 12.4 Hz, 1H, CHNO2), 6.08
(d, J=10.3 Hz, 1H, CHNO2), 7.26 (d, J=7.8 Hz, 1H,
CHarom), 7.29–7.39 (m, 5H, CHarom), 7.43 (ddd, J=1.7, 7.2,
7.7 Hz, 1H, CHarom), 7.48–7.52 (m, 1H, CHarom), 7.54 (dd,
J=1.7, 7.7 Hz, 1H, CHarom), the OH proton could not be ob-
served; 13C NMR (100 MHz CD3OD): d=42.0 (CHPh), 68.3
(CHOH), 87.1 (CHNO2), 92.5 (CHNO2), 125.6 (CHarom),
127.7 (2CHarom), 127.9 (Carom), 128.6 (2CHarom), 128.8
(Carom), 129.4 (CHarom), 129.7 (CHarom), 130.4 (CHarom), 135.8
(Carom), 137.1 (Carom); MS (EI, 70 eV): m/z (%)=222 (21),
221 [M+ÀHNO2ÀNO2] (100), 204 (21), 203 (20); anal. calcd.
for C16H14N2O5: C 61.14, H 4.49, N 8.91; found: C 61.00, H
4.50, N 8.66.
Conclusions
In summary, we have developed an organocatalytic
nitroalkane-Michael/Henry domino reaction starting
drom different g-nitro aldehydes or ketones and nitro-
alkenes. Using a hydrogen-bonding organocatalyst on
a squaramide basis, polysubstituted 1,2,3,4-tetrahydro-
naphthalen-1-ols or secondary/tertiary cyclohexanols
bearing four contiguous stereocenters were obtained
in moderate to good yields (25–84%), after crystalli-
zation in high diasteriomeric ratios (dr>95:5) and
very good to excellent enantiomeric excesses (63–
99% ee).
(1R,2S,3R,4R)-2,4-Dinitro-3-p-tolyl-1,2,3,4-tetrahydro-
naphthalen-1-ol (5b): Synthesized according to the general
procedure by using 2-(nitromethyl)benzaldehyde (3a)
(80 mg, 0.48 mmol) and (E)-1-methyl-4-(2-nitrovinyl)ben-
zene (4b) (80 mg, 0.49 mmol); colorless solid; yield: 127 mg
(81%); [a]2D5: +52.4 (c 1.04, CHCl3); 83% ee; Rf =0.69 (n-
hexane/ethyl acetate=1:1); mp 1658C. IR (film): n=3825,
3560, 3438, 2919, 2707, 2480, 2273, 2225, 2174, 2109, 2036,
1980, 1910, 1554, 1454, 1367, 1293, 1229, 1120, 1049, 926,
Experimental Section
Flash column chromatography: SIL G-25 UV254 (size 0.040–
0.063 mm) Machery&Nagel. TLC: silica gel 60 F254 plates,
Merck, Darmstadt. Visualization of the developed TLC
plates was performed with UV radiation (254 nm) or by
staining with a potassium permanganate solution. Elemental
analyses were carried out with a Vario EL element analyzer.
Melting points were determined with a Bꢁchi Melting Point
B-540 apparatus. Optical rotation values were taken on
a Perkin–Elmer P241 polarimeter. The ee values were deter-
mined by analytical HPLC with a Hewlett–Packard 1100
Series instrument using chiral stationary phases. IR spectra
were recorded on a Perkin–Elmer FT-IR Spectrum 100
spectrometer. 1H and 13C NMR spectra were measured at
ambient temperature with Varian Gemini 300, Varian Mer-
cury 300 or Varian Innova 600 spectrometers using TMS as
internal standard. Mass spectra were recorded on a Finnigan
SSQ7000 (EI 70 eV) spectrometer, high resolution mass
spectra on a Finnigan MAT 95 and high resolution ESI spec-
tra on a ThermoFisher Scientific LTQ-Orbitrap XL.
809, 773, 725 cmÀ1 1H NMR (600 MHz, CD3OD): d=2.32
;
(s, 3H, CH3), 4.64 (dd, J=10.4, 12.4 Hz, 1H, CHAr), 5.31
(d, J=3.6 Hz, 1H, CHOH), 5.59 (dd, J=3.6, 12.4 Hz, 1H,
CHNO2), 6.06 (d, J=10.4 Hz, 1H, CHNO2), 7.17 (d, J=
7.9 Hz, 2H, 2CHarom), 7.25–7.26 (m, 3H, 3CHarom), 7.44
(ddd, J=1.4, 7.5, 7.7 Hz, 1H, CHarom), 7.49–7.51 (m, 1H,
CHarom), 7.55 (dd, J=1.1, 7.7 Hz, 1H, CHarom), the OH
proton could not be observed; 13C NMR (150 MHz
CD3OD): d=19.7 (CH3), 41.6 (CHAr), 68.3 (CHOH), 87.2
(CHNO2), 92.6 (CHNO2), 125.6 (CHarom), 127.6 (2CHarom),
128.8 (Carom), 129.2 (2xCHarom), 129.4 (CHarom), 129.7
(CHarom), 130.4 (CHarom), 134.0 (Carom), 135.8 (Carom), 137.9
(Carom); MS (EI, 70 eV): m/z (%)=236 (24), 235
[M+ÀHNO2ÀNO2] (100), 218 (19), 202 (18), 143 (16), 115
(26); anal. calcd. for C17H16N2O5: C 62.19, H 4.91, N 8.53;
found: C 61.84, H 4.79, N 8.54.
(1R,2S,3R,4R)-3-(4’-Methoxyphenyl)-2,4-dinitro-1,2,3,4-
tetrahydronaphthalen-1-ol (5c): Synthesized according to
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Adv. Synth. Catal. 2013, 355, 1126 – 1136

Asymmetric Synthesis of Functionalized Tetrahydronaphthalenes
the general procedure by using 2-(nitromethyl)benzaldehyde
(3a) (83 mg, 0.50 mmol) and (E)-1-methoxy-4-(2-nitrovinyl)-
benzene (4c) (95 mg, 0.53 mmol); colorless solid; yield:
69 mg (40%); [a]25: +71.4 (c 0.28, CHCl3); 95% ee; Rf =
0.64 (n-hexane/ethDyl acetate=1:1); mp 1738C. IR (film): n=
3562, 2983, 2907, 1610, 1549, 1512, 1457, 1360, 1249, 1181,
7.58 (dd, J=1.0, 7.8 Hz, 1H, CHarom), 7.65 (dd, J=7.9,
8.0 Hz, 1H, CHarom), 7.86 (d, J=7.7 Hz, 1H, CHarom), 8.22
(dd, J=2.1, 8.3 Hz, 1H, CHarom), 8.36 (dd, J=1.9, 1.9 Hz,
1H, CHarom); 13C NMR (150 MHz CD3OD): d=41.9
(CHAr), 68.3 (CHOH), 86.8 (CHNO2), 91.9 (CHNO2),
122.6 (CHarom), 122.9 (CHarom), 125.8 (CHarom), 128.2 (Carom),
129.5 (CHarom), 130.0 (CHarom), 130.0 (CHarom), 130.4
(CHarom), 134.4 (CHarom), 135.7 (Carom), 139.6 (Carom), 148.6
(Carom); MS (EI, 70 eV): m/z (%)=295 [M+ÀH2O, ÀNO2]
(80), 266 (48), 262 (17), 249 (59), 232 (18), 202 (100), 200
(21), 189 (27), 176 (20), 127 (19), 101 (17), 76 (16); HR-MS
(ESI): m/z=313.0820, calcd. for C16H13N2O5 [M+ÀNO2]:
313.0819.
1119, 1095, 1049, 1024, 913, 827, 779, 725 cmÀ1 1H NMR
;
(400 MHz, CD3OD): d=3.77 (s, 3H, OCH3), 4.56 (br s, 1H,
OH), 4.60 (dd, J=10.4, 12.4 Hz, 1H, CHAr), 5.28 (d, J=
3.6 Hz, 1H, CHOH), 5.55 (dd, J=3.6, 12.4 Hz, 1H,
CHNO2), 6.05 (d, J=10.4 Hz, 1H, CHNO2), 6.89 (dd, J=
2.1, 6.7 Hz, 2H, 2CHarom), 7.24 (d, J=7.8 Hz, 1H, CHarom),
7.29 (dd, J=2.1, 6.7 Hz, 2H, 2CHarom), 7.43 (ddd, J=1.7,
7.3, 7.7 Hz, 1H, CHarom), 7.47–7.51 (m, 1H, CHarom), 7.53
(dd, J=1.6, 7.7 Hz, 1H, CHarom); 13C NMR (125 MHz
CD3OD): d=41.3 (CHAr), 54.3 (OCH3), 68.2 (CHOH),
87.3 (CHNO2), 92.7 (CHNO2), 114.0 (2CHarom), 125.5
(CHarom), 128.7 (Carom), 128.8 (2CHarom), 129.4 (CHarom),
129.7 (CHarom), 130.4 (CHarom), 135.6 (Carom), 135.7 (Carom),
159.6 (Carom); MS (EI, 70 eV): m/z (%)=344 [M+] (4), 280
(21), 251 (100), 234 (39), 219 (19), 218 (16), 190 (16), 189
(33), 165 (18), 143 (26), 121 (68), 115 (48), 77 (20); anal.
calcd. for C17H16N2O6: C 59.30, H 4.68, N 8.14; found: C
59.00, H 4.50, N 8.00.
(1R,2S,3R,4R)-2,4-Dinitro-3-(4’-nitrophenyl)-1,2,3,4-tetra-
hydronaphthalen-1-ol (5f): Synthesized according to the
general procedure by using 2-(nitromethyl)benzaldehyde
(3a) (86 mg, 0.52 mmol) and (E)-1-nitro-4-(2-nitrovinyl)ben-
zene (4f) (106 mg, 0.55 mmol); colorless solid; yield: 94 mg
(50%); [a]2D5: +27.4 (c 0.65, CHCl3); 91% ee; Rf =0.60 (n-
hexane/ethyl acetate=1:1); mp 1568C. IR (film): n=3511,
1603, 1553, 1514, 1349, 1115, 1057, 957, 913, 856, 766,
701 cmÀ1 1H NMR (400 MHz, CD3OD): d=4.87 (dd, J=
;
10.3, 12.3 Hz, 1H, CHAr), 5.37 (d, J=3.5 Hz, 1H, CHOH),
5.70 (dd, J=3.5, 12.2 Hz, 1H, CHNO2), 6.15 (d, J=10.2 Hz,
1H, CHNO2), 7.29 (d, J=7.7 Hz, 1H, CHarom), 7.46 (ddd,
J=1.8, 7.1, 7.8 Hz, 1H, CHarom), 7.50–7.54 (m, 1H, CHarom),
7.56 (dd, J=1.7, 7.7 Hz, 1H, CHarom), 7.67 (dd, J=2.0,
6.8 Hz, 2H, 2CHarom), 8.24 (dd, J=2.0, 6.8 Hz, 2H,
2CHarom), the OH proton could not be observed; 13C NMR
(100 MHz CD3OD): d=41.9 (CHAr), 68.3 (CHOH), 86.8
(CHNO2), 91.8 (CHNO2), 123.6 (2CHarom), 125.8 (CHarom),
128.2 (Carom), 129.1 (2CHarom), 129.5 (CHarom), 130.0
(CHarom), 130.4 (CHarom), 135.7 (CAr), 144.8 (Carom), 147.8
(Carom); MS (EI, 70 eV): m/z (%)=295 [M+ÀH2O, ÀNO2]
(54), 294 (61), 266 (50), 249 (49), 218 (21), 202 (100), 200
(37), 191 (15), 189 (34), 165 (16); HR-MS (ESI): m/z=
313.0819, calcd. for C16H13N2O5 [M+ÀNO2]: 313.0819.
(1R,2S,3R,4R)-3-(3’,4’,5’-Trimethoxyphenyl)-2,4-dinitro-
1,2,3,4-tetrahydronaphthalen-1-ol (5d): Synthesized accord-
ing to the general procedure by using 2-(nitromethyl)benzal-
dehyde (3a) (80 mg, 0.48 mmol) and (E)-1,2,3-trimethoxy-5-
(2-nitrovinyl)benzene (4d) (122 mg, 0.51 mmol); colorless
solid; yield: 139 mg (71%); [a]2D5: +82.1 (c 0.75, CHCl3);
78% ee; Rf =0.45 (n-hexane/ethyl acetate=1:1); mp 1678C.
IR (film): n=3379, 3005, 2942, 2900, 2844, 1595, 1554, 1511,
1459, 1428, 1362, 1245, 1187, 1127, 1062, 993, 932, 893, 834,
1
782, 758, 711 725 cmÀ1; H NMR (400 MHz, CD3OD): d=
3.74 (s, 3H, OCH3), 3.80 (s, 6H, 2OCH3), 4.62 (dd, J=10.4,
12.3 Hz, 1H, CHAr), 5.31 (d, J=3.6 Hz, 1H, CHOH), 5.65
(dd, J=3.6, 12.4 Hz, 1H, CHNO2), 6.10 (d, J=10.3 Hz, 1H,
CHNO2), 6.68 (s, 2H, 2xCHarom), 7.26 (d, J=7.5 Hz, 1H,
CHAr), 7.44 (ddd, J=1.7, 7.2, 7.8, 1H, CHarom), 7.48–7.52 (m,
1H, CHarom), 7.54 (dd, J=1.7, 7.7 Hz, 1H, CHarom), the OH
proton could not be observed; 13C NMR (100 MHz
CD3OD): d=42.4 (CHAr), 55.3 (2OCH3), 59.6 (OCH3),
68.3 (CHOH), 86.9 (CHNO2), 92.5 (CHNO2), 105.0
(2CHarom), 125.6 (CHarom), 128.7 (Carom), 129.4 (CHarom),
129.8 (CHarom), 130.4 (CHarom), 133.0 (Carom), 135.7 (Carom),
137.5 (Carom), 153.5 (2Carom); MS (EI, 70 eV): m/z (%)=404
[M+] (29), 340 (19), 312 (77), 311 (100), 281 (24), 280 (25),
181 (44), 168 (25), 165 (21); HR-MS (ESI): m/z=427.1112,
calcd. for C19H20N2O8Na [M+ +Na]: 427.1107.
(1R,2S,3R,4R)-3-(3’-Chlorophenyl)-2,4-dinitro-1,2,3,4-tet-
rahydronaphthalen-1-ol (5g): Synthesized according to the
general procedure by using 2-(nitromethyl)benzaldehyde
(3a) (80 mg, 0.48 mmol) and (E)-1-chloro-3-(2-nitrovinyl)-
benzene (4g) (92 mg, 0.50 mmol); colorless solid; yield:
132 mg (78%); [a]2D5: +64.6 (c 0.84, CHCl3); 97% ee; Rf =
0.67 (n-hexane/ethyl acetate=1:1); mp 1638C. IR (film): n=
3544, 1597, 1551, 1480, 1434, 1362, 1286, 1229, 1197, 1101,
1
1056, 938, 886, 780, 725 cmÀ1; H NMR (600 MHz, CD3OD):
d=4.69 (dd, J=10.3, 12.3 Hz, 1H, CHAr), 5.34 (d, J=
3.6 Hz, 1H, CHOH), 5.64 (dd, J=3.6, 12.4 Hz, 1H,
CHNO2), 6.10 (d, J=10.4 Hz, 1H, CHNO2), 7.28 (d, J=
7.8 Hz, 1H, CHarom), 7.32–7.37 (m, 3H, 3CHarom), 7.44–7.47
(m, 2H, 2CHarom), 7.51–7.53 (m, 1H, CHarom), 7.56 (dd, J=
1.3, 7.7 Hz, 1H, CHarom), the OH proton could not be ob-
served; 13C NMR (150 MHz CD3OD): d=41.8 (CHAr), 68.3
(CHOH), 86.9 (CHNO2), 92.2 (CHNO2), 125.7 (CHarom),
126.3 (CHarom), 127.9 (CHarom), 128.1 (CHarom), 128.5 (Carom),
129.5 (CHarom), 129.9 (CHarom), 130.2 (CHarom), 130.4
(CHarom), 134.5 (Carom), 135.7 (Carom), 139.5 (Carom); MS (EI,
70 eV): m/z (%)=284 (18), 257 (24), 256 (22), 255
[M+ÀHNO2, ÀNO2] (100), 238 (28), 220 (30), 202 (47), 191
(15), 115 (15); HR-MS (ESI): m/z=371.0405, calcd. for
C16H13N2O5ClNa [M+ +Na]: 371.0405.
(1R,2S,3R,4R)-2,4-Dinitro-3-(3’-nitrophenyl)-1,2,3,4-tetra-
hydronaphthalen-1-ol (5e): Synthesized according to the
general procedure by using 2-(nitromethyl)benzaldehyde
(3a) (81 mg, 0.49 mmol) and (E)-1-nitro-3-(2-nitrovinyl)ben-
zene (4e) (99 mg, 0.51 mmol); colorless solid; yield: 85 mg
(48%); [a]2D5: +52.6 (c 0.68, CHCl3); 97% ee; Rf =0.62 (n-
hexane/ethyl acetate=1:1); mp 1568C. IR (film): n=3491,
2924, 2858, 1698, 1666, 1530, 1350, 1112, 1055, 909, 812,
749 cmÀ1 1H NMR (600 MHz, CD3OD): d=4.87 (dd, J=
;
10.4, 12.3 Hz, 1H, CHAr), 5.38 (d, J=3.6 Hz, 1H, CHOH),
5.76 (dd, J=3.6, 12.3 Hz, 1H, CHNO2), 6.20 (d, J=10.3 Hz,
1H, CHNO2), 7.31 (d, J=7.9 Hz, 1H, CHarom), 7.48 (ddd,
J=1.5, 7.5, 7.7 Hz, 1H, CHarom), 7.53–7.57 (m, 1H, CHarom),
Adv. Synth. Catal. 2013, 355, 1126 – 1136
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1131

Dieter Enders et al.
1364, 1125, 1060, 964, 902, 862, 817, 751 cmÀ1 1H NMR
FULL PAPERS
(1R,2S,3R,4R)-3-(4’-Chlorophenyl)-2,4-dinitro-1,2,3,4-tet-
rahydronaphthalen-1-ol (5h): Synthesized according to the
general procedure by using 2-(nitromethyl)benzaldehyde
(3a) (88 mg, 0.53 mmol) and (E)-1-chloro-4-(2-nitrovinyl)-
benzene (4h) (100 mg, 0.55 mmol); colorless solid; yield:
156 mg (84%); [a]2D5: +58.1 (c 1.00, CHCl3); 82% ee; Rf =
0.71 (n-hexane/ethyl acetate=1:1); mp 1648C. IR (film): n=
3554, 1553, 1491, 1365, 1289, 1228, 1118, 1093, 1055, 1015,
;
(400 MHz, CD3OD): d=4.86 (dd, J=10.3, 12.3 Hz, 1H,
CHAr), 5.37 (d, J=3.6 Hz, 1H, CHOH), 5.75 (dd, J=3.6,
12.3 Hz, 1H, CHNO2), 6.21 (d, J=10.3 Hz, 1H, CHNO2),
7.28 (d, J=7.9 Hz, 1H, CHarom), 7.42–7.54 (m, 5H, 5CHarom),
7.57 (dd, J=1.5, 7.7 Hz, 1H, CHarom), 7.81–7.86 (m, 3H,
3CHarom), 7.88 (d, J=1.6 Hz, 1H, CHarom), the OH proton
could not be observed; 13C NMR (100 MHz CD3OD): d=
42.2 (CHAr), 68.4 (CHOH), 87.2 (CHNO2), 92.5 (CHNO2),
125.0 (CHarom), 125.7 (CHarom), 126.0 (CHarom), 126.1
(CHarom), 127.1 (CHarom), 127.3 (CHarom), 127.5 (CHarom),
128.5 (CHarom), 128.8 (Carom), 129.4 (CHarom), 129.8 (CHarom),
130.4 (CHarom), 133.1 (Carom), 133.4 (Carom), 134.5 (Carom),
135.8 (Carom); MS (EI, 70 eV): m/z (%)=364 [M+ÀH] (8),
272 (26), 271 (100), 254 (38), 253 (34), 252 (29), 143 (25),
141 (21), 128 (22), 127 (36), 126 (30), 115 (36); HR-MS
(ESI): m/z=387.0951, calcd. for C20H16N2O5Na [M+ +Na]:
387.0951.
948, 909, 821, 774, 709 cmÀ1; H NMR (400 MHz, CD3OD):
1
d=4.70 (dd, J=10.4, 12.3 Hz, 1H, CHAr), 5.33 (d, J=
3.5 Hz, 1H, CHOH), 5.62 (dd, J=3.6, 12.3 Hz, 1H,
CHNO2), 6.09 (d, J=10.3 Hz, 1H, CHNO2), 7.28 (d, J=
7.9 Hz, 1H, CHarom), 7.37 (dd, J=2.0, 6.5 Hz, 2H, 2xCHarom),
7.40 (dd, J=2.1, 6.5 Hz, 2H, 2CHarom), 7.45 (ddd, J=1.2,
7.5, 7.6 Hz, 1H, CHarom), 7.50–7.53 (m, 1H, CHarom), 7.56
(dd, J=0.8, 7.7 Hz, 1H, CHarom), the OH proton could not
be observed; 13C NMR (100 MHz CD3OD): d=41.5
(CHAr), 68.3 (CHOH), 87.0 (CHNO2), 92.3 (CHNO2),
125.6 (CHarom), 128.5 (Carom), 128.7 (2CHarom), 129.4
(2CHarom), 129.4 (CHarom), 129.8 (CHarom), 130.4 (CHarom),
133.8 (Carom), 135.7 (Carom), 136.0 (Carom); MS (EI, 70 eV):
m/z (%)=257 (33), 256 (20), 255 [M+ÀHNO2, ÀNO2] (100),
238 (26), 220 (30), 202 (36), 131 (16), 115 (25), 101 (21);
HR-MS (ESI): m/z=348.0507, calcd. for C16H13N2O5Cl
[M+]: 348.0508.
(1R,2S,3R,4R)-3-(2’-Furyl)-2,4-dinitro-1,2,3,4-tetrahydro-
naphthalen-1-ol (5k): Synthesized according to the general
procedure by using 2-(nitromethyl)benzaldehyde (3a)
(85 mg, 0.52 mmol) and (E)-(2-nitrovinyl)furyl (4k) (76 mg,
0.55 mmol); brownish solid; yield: 97 mg (62%); [a]2D5:
+16.3 (c 1.02, CHCl3); 64% ee; Rf =0.70 (n-hexane/ethyl
acetate=1:1); mp 1588C. IR (film) n=3464, 2918, 2566,
2062, 1738, 1548, 1453, 1360, 1287, 1194, 1144, 1096, 1061,
(1R,2S,3R,4R)-3-(3’,4’-Methylenedioxyphenyl)-2,4-dini-
tro-1,2,3,4-tetrahydronaphthalen-1-ol (5i): Synthesized ac-
cording to the general procedure by using 2-(nitromethyl)-
benzaldehyde (3a) (80 mg, 0.48 mmol) and (E)-1,2-methyl-
endioxy-4-(2-nitrovinyl)benzene (4i) (97 mg, 0.50 mmol);
colorless solid; yield: 88 mg (51%); [a]2D5: +38.4 (c 0.88,
CHCl3); 87% ee; Rf =0.64 (n-hexane/ethyl acetate=1:1);
mp 1618C. IR (film) n=3532, 2905, 1697, 1551, 1493, 1448,
1013, 935, 886, 819, 773, 741 cmÀ1 1H NMR (400 MHz,
;
CD3OD): d=4.93 (dd, J=9.5, 11.8 Hz, 1H, CHAr), 5.28 (d,
J=3.3 Hz, 1H, CHOH), 5.41 (dd, J=3.4, 11.9 Hz, 1H,
CHNO2), 6.05 (d, J=9.4 Hz, 1H, CHNO2), 6.29 (d, J=
3.1 Hz, 1H, CHarom), 6.33–6.34 (m, 1H, CHarom), 7.27 (d, J=
7.8 Hz, 1H, CHarom), 7.38–7.49 (m, 4H, 4xCHarom), the OH
proton could not be observed; 13C NMR (100 MHz
CD3OD): d=36.1 (CHAr), 68.2 (CHOH), 85.3 (CHNO2),
89.5 (CHNO2), 108.3 (CHarom), 110.3 (CHarom), 126.4
(CHarom), 128.1 (Carom), 129.4 (CHarom), 129.9 (CHarom), 130.0
(CHarom), 135.7 (Carom), 142.7 (CHarom), 150.0 (Carom); MS
(EI, 70 eV): m/z (%)=257 [M+ÀHNO2] (4), 212 (19), 211
(100), 194 (30), 183 (17), 165 (51), 155 (18), 153 (19), 152
(16), 128 (15), 115 (31); anal. calcd. for C14H12N2O6: C 55.27
H 3.98, N 9.21; found: C 54.84, H 4.29, N 8.82.
1363, 1242, 1113, 1035, 925, 859, 810, 755 cmÀ1 1H NMR
;
(400 MHz, CD3OD): d=4.58 (dd, J=10.4, 12.4 Hz, 1H,
CHAr), 5.29 (d, J=3.6 Hz, 1H, CHOH), 5.55 (dd, J=3.6,
12.4 Hz, 1H, CHNO2), 5.93 (d, J=1.2 Hz, 1H, CHH), 5.94
(d, J=1.2 Hz, 1H, CHH), 6.04 (d, J=10.4 Hz, 1H,
CHNO2), 6.77 (d, J=8.0 Hz, 1H, CHarom), 6.84 (dd, J=1.8,
8.0 Hz, 1H, CHarom), 6.88 (d, J=1.8 Hz, 1H, CHarom), 7.24
(d, J=7.7 Hz, 1H, CHarom), 7.42 (ddd, J=1.8, 7.2, 7.8 Hz,
1H, CHarom), 7.47–7.51 (m, 1H, CHarom), 7.53 (dd, J=1.8,
7.7 Hz, 1H, CHarom), the OH proton could not be observed;
13C NMR (100 MHz CD3OD): d=41.2 (CHAr), 68.2
(CHOH), 87.1 (CHNO2), 92.6 (CHNO2), 101.3 (CH2), 107.7
(CHarom), 108.1 (CHarom), 121.5 (CHarom), 125.5 (CHarom),
128.8 (Carom), 129.4 (CHarom), 129.7 (CHarom), 130.4 (CHarom),
130.5 (Carom), 135.7 (Carom), 147.6 (Carom), 148.2 (Carom); MS
(EI, 70 eV): m/z (%)=358 [M+] (18), 294 (27), 266 (26), 265
(100), 248 (50), 235 (29), 207 (24), 190 (15), 189 (55), 178
(23), 165 (16), 148 (37), 135 (49), 124 (22), 121 (20), 119
(22), 118 (16), 115 (21), 94 (17), 91 (33), 89 (27), 65 (23), 63
(1R,2S,3R,4S)-5-Methoxy-2,4-dinitro-3-phenyl-1,2,3,4-tet-
rahydronaphthalen-1-ol (5l): Synthesized according to the
general procedure by using 3-methoxy-2-(nitromethyl)ben-
zaldehyde (3l) (104 mg, 0.53 mmol) and (E)-(2-nitrovinyl)-
benzene (4a) (85 mg, 0.57 mmol); colorless solid; yield:
75 mg (41%); [a]25: À167.3 (c 0.89, CHCl3); 70% ee; Rf =
0.47 (n-hexane/ethDyl acetate=1:1); mp 1998C. IR (film): n=
3571, 3472, 3006, 2936, 1696, 1596, 1547, 1472, 1363, 1331,
1268, 1188, 1088, 1053, 1011, 974, 925, 853, 810, 784, 747
741 cmÀ1 1H NMR (600 MHz, CD3OD): d=3.80 (s, 3H,
;
OCH3), 4.49 (dd, J=6.1, 12.8 Hz, 1H, CHPh), 5.43 (d, J=
4.0 Hz, 1H, CHOH), 6.01 (dd, J=4.0, 12.8 Hz, 1H,
CHNO2), 6.15 (d, J=6.1 Hz, 1H, CHNO2), 7.05 (d, J=
8.3 Hz, 1H, CHarom), 7.17 (d, J=7.7 Hz, 1H, CHarom), 7.27–
7.35 (m, 5H, 5CHarom), 7.54 (dd, J=8.1, 8.1 Hz, 1H,
CHarom), the OH proton could not be observed; 13C NMR
(150 MHz CD3OD): d=39.7 (CHPh), 54.9 (CH3), 68.0
(CHOH), 84.1 (CHNO2), 86.7 (CHNO2), 110.5 (CHarom),
117.0 (Carom), 122.1 (CHarom), 126.6 (2CHAr), 127.7 (CHAr),
128.6 (2CHarom), 131.8 (CHarom), 135.9 (Carom), 138.3 (Carom),
157.4 (Carom); MS (EI, 70 eV): m/z (%)=298 [M+ÀNO2] (3),
(17);
HR-MS
(ESI):
m/z=381.0692,
calcd.
for
C17H14N2O7Na [M+ +Na]: 381.0693.
(1R,2S,3R,4R)-3-(2’-Naphthyl)-2,4-dinitro-1,2,3,4-tetrahy-
dronaphthalen-1-ol (5j): Synthesized according to the gener-
al procedure by using 2-(nitromethyl)benzaldehyde (3a)
(82 mg, 0.50 mmol) and (E)-2-(2-nitrovinyl)naphthalene (4j)
(105 mg, 0.53 mmol); colorless solid; yield: 123 mg (68%);
[a]25: +71.0 (c 1.01, CHCl3); 92% ee; Rf =0.68 (n-hexane/
ethDyl acetate=1:1); mp 1688C. IR (film): n=3853, 3061,
2913, 2653, 2290, 2108, 2065, 1984, 1912, 1550, 1454, 1364,
1132
asc.wiley-vch.de
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 1126 – 1136

Asymmetric Synthesis of Functionalized Tetrahydronaphthalenes
251 (100), 236 (17); HR-MS (ESI): m/z=298.1074, calcd. for
C17H16N1O4 [M+ÀNO2]: 298.1074.
(100 MHz CD3OD): d=29.0 (CH2), 27.8 (CH2), 50.1
(CHPh), 70.6 (CHOH), 87.3 (CHNO2), 94.3 (CHNO2),
127.9 (CHarom), 128.3 (2CHarom), 128.5 (2CHarom), 134.1
(Carom); MS (EI, 70 eV): m/z (%)=266 [M+] (28), 189 (24),
174 (16), 173 (100), 172 (22), 171 (15), 155 (33), 146 (16),
145 (57), 143 (30), 131 (22), 130 (15), 129 (59), 128 (37), 117
(34), 116 (15), 115 (56), 105 (43), 103 (16), 91 (96), 77 (24),
67 (17), 55 (15); HR-MS (ESI): m/z=266.0900, calcd. for
C12H14N2O5 [M+]: 266.0897.
(1R,2S,3R,4R)-6-Bromo-2,4-dinitro-3-phenyl-1,2,3,4-tetra-
hydronaphthalen-1-ol (5m): Synthesized according to the
general procedure by using 4-bromo-2-(nitromethyl)benzal-
dehyde (3m) (130 mg, 0.53 mmol) and (E)-(2-nitrovinyl)ben-
zene (4a) (83 mg, 0.56 mmol); colorless solid; yield: 73 mg
(35%); [a]2D5: +19.1 (c 0.90, CHCl3); 97% ee; Rf =0.74 (n-
hexane/ethyl acetate=1:1); mp 1168C. IR (film): n=3499,
2922, 2855, 1703, 1553, 1486, 1362, 1287, 1189, 1117, 1053,
(1R,2S,3R,4S)-1-Methyl-2,4-dinitro-3-phenylcyclohexan-1-
ol (11a): Synthesized according to the general procedure by
using 5-nitropentan-2-one (10) (71 mg, 0.54 mmol) and (E)-
(2-nitrovinyl)benzene (4a) (85 mg, 0.57 mmol); colorless
solid; yield: 93 mg (61%); [a]2D5: À15.1 (c 1.00, CHCl3); 94%
ee; Rf =0.65 (n-hexane/ethyl acetate=1:1); mp 1828C. IR
(film): n=3559, 2939, 1737, 1548, 1495, 1451, 1373, 1327,
1290, 1137, 1089, 1031, 949, 917, 887, 825, 761, 729,
1
922, 874, 824, 761 cmÀ1; H NMR (600 MHz, CD3OD): d=
4.69 (dd, J=10.1, 12.2 Hz, 1H, CHPh), 5.30 (d, J=3.5 Hz,
1H, CHOH), 5.59 (dd, J=3.6, 12.3 Hz, 1H, CHNO2), 6.07
(d, J=10.4 Hz, 1H, CHNO2), 7.30–7.39 (m, 5H, 5CHarom),
7.43 (s, 1H, CHarom), 7.48 (d, J=8.3 Hz, 1H, CHarom), 7.68
(dd, J=1.9, 8.3 Hz, 1H, CHarom), the OH proton could not
be observed; 13C NMR (150 MHz CD3OD): d=39.6
(CHPh), 67.8 (CHOH), 87.0 (CHNO2), 91.6 (CHNO2),
122.9 (Carom), 127.7 (2CHarom), 128.0 (CHarom), 128.7
(2CHarom), 128.7 (CHarom), 130.8 (Carom), 132.1 (CHarom),
133.0 (CHarom), 135.2 (Carom), 136.9 (Carom); MS (EI, 70 eV):
m/z (%)=330, 328 [M+ÀH2O, ÀNO2] (47, 50), 301 (63), 299
(57), 284 (15), 283 (23), 282 (36), 249 (17), 220 (100), 203
(24), 202 (82), 191 (19), 126 (15), 115 (17), 91 (15), 77 (18);
HR-MS (ESI): m/z=414.9901, calcd. for C16H13N2O5BrNa
[M+ +Na]: 414.9900.
701 cmÀ1 1H NMR (400 MHz, CD3OD): d=1.32 (s. 3H,
;
CH3), 1.85 (ddd, J=4.0, 13.9, 14.2 Hz, 1H, CHH), 1.96 (ddd,
J=3.1, 4.3, 14.3 Hz, 1H, CHH), 2.14 (dddd, J=3.1, 4.0, 4.0,
12.4 Hz, 1H, CHH), 2.47 (dddd, J=4.3, 12.5, 12.5, 13.7, 1H,
CHH), 4.18 (dd, J=11.8, 11.8 Hz, 1H, CHPh), 4.95 (ddd,
J=4.3 Hz, 11.9, 11.9 Hz, 1H, CHNO2), 5.02 (d, J=12.0 Hz,
1H, CHNO2), 7.23–7.32 (m, 5H, 5CHarom,) the OH proton
could not be observed; 13C NMR (100 MHz CD3OD): d=
25.4 (CH3), 26.3 (CH2), 35.6 (CH2), 45.8 (CHPh), 68.9
(CCH3OH), 88.7 (CHNO2), 94.1 (CHNO2), 127.9 (CHarom),
128.3 (4CHarom), 135.4 (Carom); MS (EI, 70 eV): m/z (%)=
280 [M+] (61), 187 (75), 186 (42), 185 (15), 173 (17), 171
(16), 169 (35), 158 (39), 157 (25), 156 (16), 149 (18), 145
(39), 144 (17), 143 (90), 131 (21), 130 (22), 129 (69), 128
(58), 127 (20), 117 (61), 116 (19), 115 (68), 105 (86), 103
(22), 91 (100), 77 (35), 71 (29), 65 (17), 55 (16); anal. calcd.
for C13H16N2O5: C 55.71 H 5.75, N 9.99; found: C 55.46, H
5.24, N 9.69.
(1R,2S,3R,4R)-7-Fluoro-2,4-dinitro-3-phenyl-1,2,3,4-tetra-
hydronaphthalen-1-ol (5n): Synthesized according to the
general procedure by using 5-fluoro-2-(nitromethyl)benzal-
dehyde (3n) (90 mg, 0.49 mmol) and (E)-(2-nitrovinyl)ben-
zene (4a) (84 mg, 0.51 mmol); brownish oil; yield: 73 mg
(45%); [a]2D5: +8.0 (c 0.20, CHCl3); 77% ee; Rf =0.76 (n-
hexane/ethyl acetate=1:1). IR (film): n=3480, 2922, 2286,
2110, 2070, 1990, 1922, 1740, 1607, 1553, 1500, 1446, 1362,
1250, 1151, 1110, 1056, 877, 821, 758 cmÀ1
;
1H NMR
(600 MHz, CD3OD): d=4.69 (dd, J=10.1, 12.3 Hz, 1H,
CHPh), 5.31 (d, J=3.6 Hz, 1H, CHOH), 5.62 (dd, J=3.6,
12.2 Hz, 1H, CHNO2), 6.05 (d, J=10.0 Hz, 1H, CHNO2),
7.22 (ddd, J=2.8, 8.5, 8.6 Hz, 1H, CHarom), 7.29–7.39 (m,
7H, 7CHarom), the OH proton could not be observed;
(1R,2S,3R,4S)-3-(4’-Chlorophenyl)-1-methyl-2,4-dinitrocy-
clohexan-1-ol (11b): Synthesized according to the general
procedure by using 5-nitropentan-2-one (10) (63 mg,
0.48 mmol) and (E)-1-chloro-4-(2-nitrovinyl)benzene
4
(R1 =4-ClC6H4) (89 mg, 0.48 mmol); colorless solid; yield:
100 mg (77%); [a]2D5: À21.6 (c 0.70, CHCl3); 89% ee; Rf =
0.61 (n-hexane/ethyl acetate=1:1); mp 1108C. IR (film): n=
3554, 2968, 1549, 1493, 1451, 1371, 1285, 1179, 1132, 1093,
13C NMR (150 MHz CD3OD): d=42.0 (CHPh), 67.9
2
(CHOH), 87.0 (CHNO2), 91.8 (CHNO2), 116.3 (d, JC,F
=
22.3 Hz, CHarom), 116.6 (d, 2JC,F =22.3 Hz, CHarom), 126.9
3
1
(Carom), 127.7 (2CHarom), 127.9 (CHarom), 128.4 (d, JC,F
=
1029, 918, 891, 822, 755 cmÀ1; H NMR (600 MHz, CD3OD):
8.7 Hz, CHarom), 128.7 (2CHarom, Carom), 137.1 (Carom), 163.2
d=1.32 (s, 3H, CH3), 1.84 (ddd, J=4.0, 14.0, 14.1 Hz, 1H,
CHH), 1.96 (ddd, J=3.1, 4.2, 14.3 Hz, CHH), 2.15 (dddd,
J=3.1, 4.0, 4.0, 12.4 Hz, 1H, CHH), 2.47 (dddd, J=4.2, 12.4,
12.4, 13.8 Hz, 1H, CHH), 4.19 (dd, J=11.8, 11.8 Hz, 1H,
CHAr), 4.93 (ddd, J=4.4, 11.8, 11.9 Hz, 1H, CHNO2), 5.01
(d, J=12.0 Hz, 1H, CHNO2), 7.27–7.32 (m, 4H, 4CHarom),
the OH proton could not be observed; 13C NMR (150 MHz
CD3OD): d=25.4 (CH3), 26.3 (CH2), 35.6 (CH2), 45.3
(CHAr), 68.9 (CCH3OH), 88.5 (CHNO2), 93.9 (CHNO2),
128.4 (2CHarom), 129.9 (2CHarom), 133.9 (Carom), 134.3
(Carom); MS (EI, 70 eV): m/z (%)=316, 314 [M+] (31, 97),
237 (20), 223 (31), 222 (38), 221 (93), 220 (96), 207 (22), 206
(18), 205 (15), 204 (35), 203 (44), 194 (23), 193 (25), 192
(68), 191 (42), 190 (22), 179 (53), 177 (73), 168 (15), 167
(33), 165 (39), 163 (30), 153 (27), 152 (22), 151 (47), 149
(16), 143 (16), 142 (25), 141 (73), 139 (100), 129 (44), 128
(64), 127 (71), 125 (75), 116 (30), 115 (84), 102 (19), 101
(27), 99 (27), 91 (16), 83 (29), 81 (22), 77 (30), 75 (17), 71
1
(d, JC,F =248.3 Hz, CF); 19F NMR (565 MHz, CD3OD): d=
À113.1; MS (EI, 70 eV): m/z (%)=286 [M+ÀNO2] (1), 239
(100), 220 (19); HR-MS (ESI): m/z=355.0700, calcd. for
C16H13N2O5FNa [M+ +Na]: 355.0701.
(1S,2S,3R,4S)-2,4-Dinitro-3-phenylcyclohexan-1-ol (1-epi-
8): Synthesized according to the general procedure by using
4-nitrobutanal (7) (60 mg, 0.51 mmol) and (E)-(2-nitrovi-
nyl)benzene (4a) (85 mg, 0.57 mmol); colorless solid; yield:
34 mg (25%); [a]25: À24.1 (c 1.00, CHCl3); 97% ee; mp
1458C. IR (film):Dn=2924, 2855, 1736, 1547, 1494, 1453,
1
1372, 1284, 1214, 1068, 1014, 981, 861, 760 cmÀ1; H NMR
(400 MHz, CD3OD): d=1.70–1.82 (m, 1H, CHH), 2.17–2.24
(m, 2H, 2CHH), 2.36–2.42 (m, 1H, CHH), 3.73 (dd, J=
11.7, 11.7 Hz, 1H, CHPh), 4.20 (ddd, J=4.5, 9.7, 14.0 Hz,
CHOH), 4.76 (dd, J=9.7, 11.9 Hz, 1H, CHNO2), 5.06 (ddd,
J=4.3, 11.7, 11.7 Hz, 1H, CHNO2), 7.22–7.34 (m, 5H,
5CHarom), the OH proton could not be observed; 13C NMR
Adv. Synth. Catal. 2013, 355, 1126 – 1136
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1133

Dieter Enders et al.
FULL PAPERS
(44); HR-MS (ESI): m/z=314.0663, calcd. for C13H15N2O5Cl References
[M+]: 314.0664.
(1R,2S,3R,4S)-1-Methyl-2,4-dinitro-3-(3’-nitrophenyl)cy-
clohexan-1-ol (11c): Synthesized according to the general
procedure by using 5-nitropentan-2-one (10) (71 mg,
0.54 mmol) and (E)-1-nitro-3-(2-nitrovinyl)benzene 4 (R1 =
3-NO2C6H4) (107 mg, 0.55 mmol); colorless solid; yield:
120 mg (68%); [a]2D5: À9.6 (c 0.57, CH3OH); 91% ee; Rf =
0.58 (n-hexane/ethyl acetate=1:1); mp 1888C. IR (film) n=
3582, 3082, 2935, 2646, 1536, 1454, 1352, 1122, 1032, 913,
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868, 815, 730 cmÀ1 1H NMR (600 MHz, CD3OD): d=1.37
;
(s, 3H, CH3), 1.91 (ddd, J=4.0, 14.0, 14.2 Hz, 1H, CHH),
2.01 (ddd, J=3.4, 3.9, 14.4 Hz, 1H, CHH), 2.22 (dddd, J=
3.1, 4.0, 4.0, 12.5 Hz, 1H, CHH), 2.52 (dddd, J=4.2, 12.5,
12.5, 13.8 Hz, 1H, CHH), 4.39 (dd, J=11.7, 11.7 Hz, 1H,
CHAr), 5.07 (ddd, J=4.3, 11.8, 11.8 Hz, 1H, CHNO2), 5.17
(d, J=11.9 Hz, 1H, CHNO2), 7.58 (dd, J=8.0, 8.0 Hz, 1H,
CHarom), 7.77 (d, J=7.5 Hz, 1H, CHarom), 8.17 (ddd, J=1.0,
2.2, 8.3 Hz, 1H, CHarom), 8.31 (s, 1H, CHarom), the OH
proton could not be observed; 13C NMR (150 MHz
CD3OD): d=25.4 (CH3), 26.3 (CH2), 35.6 (CH2), 45.7
(CHAr), 68.9 (CCH3OH), 88.2 (CHNO2), 93.7 (CHNO2),
122.9 (CHarom), 123.0 (CHarom), 129.7 (CHarom), 135.0
(CHarom), 137.9 (Carom), 148.4 (Carom); MS (EI, 70 eV): m/z
(%)=325 [M+] (27), 232 (100), 218 (58), 215 (20), 214 (45),
207 (27), 203 (25), 202 (50), 190 (69), 188 (31), 184 (16), 172
(16), 171 (18), 168 (24), 167 (24), 154 (16), 152 (22), 150
(33); HR-MS (ESI) m/z=348.0803, calcd. for C13H15N3O7Na
[M+ +Na]: 348.0802.
(1R,2S,3R,4S)-3-(2’-Bromophenyl)-1-methyl-2,4-dinitrocy-
clohexan-1-ol (11d): Synthesized according to the general
procedure by using 5-nitropentan-2-one (10) (73 mg,
0.56 mmol) and (E)-1-bromo-2-(2-nitrovinyl)benzene
4
(R1 =2-BrC6H4) (130 mg, 0.57 mmol); colorless solid; yield:
94 mg (47%); [a]25: À10.3 (c 0.84, CHCl3); 87% ee; mp
1518C. IR (film):Dn=3579, 3292, 2918, 2852, 2008, 1731,
1547, 1471, 1367, 1285, 1248, 1177, 1129, 1031, 949, 916, 889,
820, 768, 722 cmÀ1 1H NMR (600 MHz, CD3OD): d=1.33
;
(s, 3H, CH3), 1.84 (ddd, J=4.1, 14.0, 14.1 Hz, 1H, CHH),
1.97 (ddd, J=3.1, 4.3, 14.3 Hz, 1H, CHH), 2.13 (dddd, J=
3.0, 4.0, 4.0, 12.7 Hz, 1H, CHH), 2.55 (dddd, J=4.4, 12.0,
12.6, 13.8 Hz, 1H, CHH), 4.85–4.92 (m, 1H, CHNO2), 4.98–
5.00 (m, 2H, CHNO2, CHAr), 7.13 (ddd, J=1.7, 7.4, 8.1 Hz,
1H, CHarom), 7.35 (ddd, J=1.3, 7.5, 7.7 Hz, 1H, CHarom),
7.51 (dd, J=1.3, 8.1, 1H, CHarom), 7.64 (dd, J=1.6, 7.9 Hz,
1H, CHarom), the OH proton could not be observed;
13C NMR (150 MHz CD3OD): d=25.4 (CH3), 26.1 (CH2),
35.5 (CH2), 43.7 (CHAr), 69.0 (CCH3OH), 88.3 (CHNO2),
94.2 (CHNO2), 126.0 (Carom), 127.7 (CHarom), 128.0 (CHarom),
129.3 (CHarom), 133.4 (CHarom), 135.1 (Carom); MS (EI,
70 eV): m/z (%)=360, 358 [M+] (58, 62), 279 (91), 266 (33),
265 (32), 249 (23), 247 (16), 223 (28), 221 (25), 202 (68), 185
(36), 183 (23), 171 (40), 169 (33), 168 (61), 159 (20), 154
(16), 152 (15), 145 (18), 144 (23), 143 (23), 142 (41), 141
(35), 131 (17), 130 (19), 129 (44), 128 (100), 127 (15), 116
(53), 115 (87), 102 (25), 101 (15), 99 (15), 91 (19), 89 (16), 83
(21), 77 (24), 71 (31); HR-MS (ESI): m/z=358.0159, calcd.
for C13H15N2O5Br [M+]: 358.0159.
1134
asc.wiley-vch.de
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 1126 – 1136

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