Rhodium-catalyzed asymmetric nitroallylation of arylmetallics with cyclic nitroallyl acetates and applications in organic synthesis

Article abstract of DOI:10.1002/ejoc.200600275

Highly enantioselective rhodium-catalyzed nitroallylations of arylboronic acids and arylzinc chlorides with cyclic nitroallyl acetates are described. Catalyst screening indicated that the rhodium complex of [Rh(OH)(CODJ] ₂ and optically pure bi

Full text of DOI:10.1002/ejoc.200600275

FULL PAPER
DOI: 10.1002/ejoc.200600275
Rhodium-Catalyzed Asymmetric Nitroallylation of Arylmetallics with Cyclic
Nitroallyl Acetates and Applications in Organic Synthesis
Lin Dong,[a,c] Yan-Jun Xu,[a] Wei-Cheng Yuan,[a,c] Xin Cui,[a] Lin-Feng Cun,[a] and
Liu-Zhu Gong*[a–c]
Keywords: Asymmetric catalysis / Nitroallylation / Rhodium complexes / (+)-β-Lycorane / (+)-γ-Lycorane / Chiral nitroal-
kenes
Highly enantioselective rhodium-catalyzed nitroallylations of
arylboronic acids and arylzinc chlorides with cyclic nitroallyl
acetates are described. Catalyst screening indicated that the
rhodium complex of [Rh(OH)(COD)]2 and optically pure bi-
nap is the optimal catalyst for the nitroallylation of aryl-
boronic acids with 2-nitrocyclohex-2-enyl esters, providing
good yields and high enantioselectivities of up to 99% ee.
The rhodium complex prepared from Rh(acac)(C2H4)2 and
(R)-binap efficiently catalyzed the nitroallylation of arylzinc
chlorides with 2-nitrocyclohex-2-enyl acetate at 0 °C in high
yields of up to 93% and with high enantioselectivities of up
to 96% ee. A number of synthetically useful intermediates
with high optical purity were prepared with this reaction as
starting point: concise total syntheses of optically pure (+)-β-
lycorane in 53% overall yield and of (+)-γ-lycorane in 52%
overall yield were achieved by commencing with the asym-
metric nitroallylation of 3,4-methylenedioxyphenylzinc chlo-
ride with 2-nitrocyclohex-2-enyl acetate.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
Introduction
Organic molecules that contain multiple functionalities
are always synthetically useful in organic chemistry because
they can be transformed into a variety of substances
through transformation of the functional groups in dif-
ferent organic reactions. Nitroallyl acetates 1, as first devel-
oped by Seebach and Knochel,[1] can undergo tandem reac-
tion sequences involving conjugated addition and ester
group elimination to yield nitroolefins 2, whilst Michael ad-
dition of further nucleophiles to the nitroolefins 2 produces
nitroalkanes 3 [Equation (1)], which can be further trans-
formed into a variety of useful compounds as the nitro
group can be converted into various functionalities.[2] The
utilities of these transformations involving nitroallyl ace-
tates have been demonstrated by their applications in the
organic syntheses of heterocycles and nonnatural prod-
ucts.[3] Despite these versatile applications, this useful trans-
formation has not yet been operated as a catalytic asymmet-
ric process.
(1)
In contrast, asymmetric conjugated addition reactions of
organometallics to nitroalkenes mediated by transition
metal complexes have been documented.[4,5] Of those, the
asymmetric addition of arylboronic acids to nitroolefins
with catalysis by a rhodium complex of (S)-binap, recently
discovered by Hayashi and co-workers,[5] has emerged as an
efficient method for the preparation of optically enriched
nitro-containing compounds.
[a] Key Laboratory for Asymmetric Synthesis and Chirotechnol-
ogy of Sichuan Province, Chengdu Institute of Organic Chemis-
try, Chinese Academy of Sciences,
Inspired by works from Seebach and Hayashi and co-
workers,[1,2,5] we investigated reactions between 2-nitrocy-
clohex-2-enol esters 1 and arylboronic acids in the presence
of chiral rhodium complexes.[6] Our preliminary results in-
deed indicated that the asymmetric nitroallylation of aryl-
boronic acids with cyclic nitroallyl acetate 1a and its struc-
tural analogues in the presence of chiral rhodium complexes
proceeded smoothly, affording the chiral cyclic nitroalkenes
2 with high enantioselectivities, but in unsatisfactory yields.
Chengdu, 610041, China
Fax: +86-28-85223978
E-mail: gonglz@cioc.ac.cn
[b] Hefei National Laboratory for Physical Sciences at the Micro-
scale and Department of Chemistry, University of Science and
Technology of China,
Hefei, 230026, China
[c] Graduate School of Chinese Academy of Sciences,
Beijing, China
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In this paper we describe highly enantioselective nitroal- sis with a rhodium complex of Rh(acac)(C2H4)2 with (R)-
lylations of arylboronic acids and arylzinc reagents with cy- binap under the standard conditions that had been used
clic nitroallyl acetates 1,[7] promoted by rhodium complexes for rhodium-catalyzed 1,4-additions of arylboronic acids to
of optically pure binap and a number of its derivatives 4–6 nitroalkenes.[5] We were delighted to observe that the reac-
(Figure 1). The resulting nitroalkenes 2 are readily con- tion gave the desired product 2a, the structure of which was
verted into a variety of optically active compounds 7 [Equa- confirmed by X-ray diffraction (Figure 2), with a high
tion (2)], as a result of which concise syntheses of optically enantioselectivity of 94% ee (Table 1, Entry 1). The abso-
pure (+)-γ-lycorane (8)[8,9] and (+)-β-lycorane (9)[10] are fin- lute configuration of the stereogenic center was determined
ished in high overall yields with this reaction as starting to be R by correlation with a known compound 11, which
point.
was derived from 2a by a two-step reaction sequence involv-
ing a reduction and a functional group transformation of
the nitro into a carbonyl group (Scheme 1).[5]
Figure 2. X-ray structure of 2a (CCDC-289193).
Table 1. Rhodium-catalyzed asymmetric nitroallylation of phen-
ylboronic acid with 2-nitrocyclohex-2-enyl esters 1.[a]
Figure 1. The chiral ligands evaluated in this study.
Entry Metal
Ligand
1
Temp. Time Yield ee
(oC)
(h)
(%)[b] (%)[c]
1
2
3
4
5
6
7
8
Rh(acac)(C2H4)2
(R)-BINAP 1a 100
(R)-BINAP 1b 100
(R)-BINAP 1c 100
(R)-BINAP 1a 100
(R)-BINAP 1a 50
5
5
5
5
30
30
48
20
41
55
56
43
51
48
36
44
36
45
48
94
95
93
94
94
97
97
97
94
90
95
86
97
77
90
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
[RhCl(COD)]2
Rh(acac)(C2H4)2
[Rh(OH)(COD)]2 (R)-BINAP 1a 50
[Rh(OH)(COD)]2 (S)-BINAP
[Rh(OH)(COD)]2 4a
[Rh(OH)(COD)]2 4b
[Rh(OH)(COD)]2 4c
[Rh(OH)(COD)]2 4d
[Rh(OH)(COD)]2 5a
[Rh(OH)(COD)]2 5b
[Rh(OH)(COD)]2 6a
[Rh(OH)(COD)]2 6b
20
20
20
20
20
20
20
50
20
20
20
1a 50
1a 50
1a 50
1a 50
1a 50
1a 50
1a 50
1a 50
1a 50
(2)
9
10
11
12
13
14
15
[a] Treatment of arylboronic acid was performed in the presence
of 5 mol-% rhodium complex and 6 mol-% (R)-binap in a solvent
mixture of dioxane/H2O = 10:1. [b] Isolated yield. [c] The ee values
were determined by GC.
Results and Discussion
The product 2a, however, was isolated in only 30% yield
as the starting substrate 1a decomposed at 100 °C, so fur-
ther optimization of the reaction conditions was required
Enantioselective Nitroallylation of Arylboronic Acids and
Arylzinc Chlorides with Cyclic Nitroallyl Acetates
We first investigated nitroallylation of phenylboronic (Table 1). The use of 2-nitrocyclohex-2-enyl pivalate (1b) to
acid with 2-nitrocyclohex-2-enyl acetate (1a)[1] with cataly- replace 1a as a substrate did not suppress the decomposi-
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Asymmetric Nitroallylation of Arylmetallics
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(S)-binap, which catalyzed the reaction in good yield with
97% ee at 50 °C, with minimization of the decomposition
of 1a (Entries 6 and 7).
The rhodium complexes of the 7,7Ј-disubstituted binaps
4–6, prepared starting with asymmetric oxidative coup-
ling,[12] and [Rh(OH)(COD)]2 were also examined for the
model reaction (Entries 8–15), which indicated that the sub-
stitution of the ligand has a considerable influence over the
stereocontrol. Of these ligands, 4a and 5b exhibited higher
enantioselectivities than their structural analogues, though
much lower enantioselectivities of 86% and 77% ee were
observed with rhodium complexes formed from
[Rh(OH)(COD)]2 and 5a and 6a, respectively (Entries 12
and 14). The effect of the substituent on the enantio-
selectivity might be a function of variation of the dihedral
angle.[13] Although comparable enantioselectivities was ob-
served with 4a and 5b, the yields were lower than those
with binap (Entries 6–8 and 13), so the rhodium complex of
[Rh(OH)(COD)]2 and binap can be regarded as an optimal
catalyst system in terms both of catalytic activity and of
enantioselectivity.
Scheme 1. The conversion of 2a into (R)-2-phenylcyclohexanone
(11) for determination of the absolute configuration of 2a.
tion, and a low yield was still observed, though with the
enantioselectivity maintained (Table 1, Entry 2). Although
a higher yield was observed with 1c, the enantioselectivity
was decreased slightly (Entry 3), whilst the yield could be
slightly improved to 41% by performing the reaction at
50 °C (Entry 4). Screening of the transition metal source
The scope of the optimal catalyst generated from
revealed [Rh(OH)(COD)]2[11] to be a better precatalyst (En- [Rh(OH)(COD)]2 and (S)-binap was then extended to cata-
tries 1–6), so further improvement in the yield and the lyze the nitroallylation of a range of arylboronic acids bear-
enantioselectivity was achieved by using a rhodium com- ing either electron-donating or electron-withdrawing sub-
plex generated in situ from [Rh(OH)(COD)]2 and (R)- or stituents with cyclic nitroallyl acetates 1a and 1d. As shown
Table 2. Scope and limitations of the rhodium-catalyzed asymmetric nitroallylation of arylboronic acids.[a]
[a] The reaction of arylboronic acid was performed in the presence of 5 mol-% Rh and 6 mol-% (S)-binap in a solvent mixture of dioxane/
H2O = 10:1. [b] Isolated yield. [c] The ee values were determined by GC or HPLC.
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in Table 2, the reactions between 2-nitrocyclohex-2-enyl below room temperature. To improve the yield, asymmetric
acetate (1a) and arylboronic acids gave the desired products nitroallylation of 1a with arylzinc was investigated
in good yields and with excellent enantioselectivities rang- (Table 3).
ing from 90–99% ee (Entries 1–9). The electronic nature of
The asymmetric nitroallylation was examined in the pres-
the substituents in the arylboronic acids did not signifi- ence of a rhodium complex of Rh(acac)(C2H4)2 and (R)-
cantly affect the reaction, but the enantioselectivity did to binap as a catalyst and phenylzinc chloride as a nucleophilic
some degree depend on the steric bulkiness of the aryl- species. The organozinc is indeed more reactive than the
boronic acids: an enantioselectivity of only 90% ee, for ex- organoboronic acid toward the nitroallyl acetate: the nitro-
ample – much lower than those of its structural analogues – allylation of phenylzinc chloride with 1a proceeded
was observed for 4-tert-butylphenylboronic acid (Entry 6). smoothly at 20 °C and even at 0 °C, giving rise to 2a in high
The stereoselectivity of this type of reaction is also quite yields ranging from 75% to 93% (Entries 1–4). The solvent
sensitive to the ring size of the cyclic nitroallyl acetate: dramatically affects the enantioselectivity: use of THF as a
much lower enantioselectivity was observed in, for example, solvent gave the highest enantioselectivity, of 85% ee at
the reaction between 2-nitrocyclopent-2-enyl acetate (1d) 20 °C (Entry 1) and improved to 93% ee by conducting the
and phenylboronic acid (Entry 10).
reaction at 0 °C (Entry 5). Asymmetric nitroallylations of
Conducting the rhodium-catalyzed asymmetric nitroal- some other arylzinc compounds with 1a were also studied
lylation at low temperature generally prevents the decompo- under these reaction conditions (Entries 6–11): the nitroal-
sition of the 2-nitrocyclohex-2-enyl esters, such decomposi- lylations of arylzinc chlorides proceeded at 0 °C to generate
tion being a possible reason for the low yield. Use of more the products in much higher yields than obtained with aryl-
reactive arylmetallic species to replace arylboronic acids boronic acids, but the enantioselectivity had decreased by
may make the reaction proceed at a lower temperature so small amounts, probably due to the occurrence of the back-
that the yield might be improved. Conjugated additions of ground reaction. Excellent enantioselectivities were
arylzinc compounds to electron-deficient unsaturated ole- observed, though, in the cases of 4-fluorophenyl-, phenyl-,
fins catalyzed by rhodium complexes have been discov- and 3,4-methylenedioxyphenylzinc chlorides (Entries 5, 8,
ered,[7a] and in this case the reaction can be carried out and 10).
Table 3. The nitroallylation of PhZnCl acetic acid with 2-nitrocyclohex-2-enyl ester 1a.[a]
[a] Treatment of organozinc reagents was performed in the presence of 3 mol-% Rh(acac)(C2H4)2 and 3.3 mol-% (R)-binap in THF.
[b] Isolated yield. [c] The ee values were determined by GC or HPLC.
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Asymmetric Nitroallylation of Arylmetallics
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Mechanism Consideration
enantiomeric excess (98% ee).[16] The relative configuration
between the two contiguous stereogenic carbon atoms in
7a was identified as cis by X-ray crystallographic analysis
(Figure 3). Following treatment with DABCO, the com-
A plausible mechanism to account for the results ob-
tained in the reaction is proposed in Scheme 2. The reaction
is considered to begin with a transmetalation between the
chiral rhodium complex of binap and an arylboronic acid
or an arylzinc chloride to form the arylrhodium(I) species
A,[14] and the insertion of the carbon–carbon double bond
of the nitroallyl acetate into the Ar–Rh bond produces a
key intermediate B,[5,14] which undergoes a β-elimination of
the ester group to regenerate the catalyst and liberate the
product 2.[15]
Scheme 3. Conversion of 2i to methyl 3-[6-(benzo[1,3]dioxol-5-yl)-
3-hydroxycyclohex-1-enyl]propionate (12).
Scheme 2. A plausible mechanism for the asymmetric nitroal-
lylation.
Application in the Synthesis of Chiral Synthetically Useful
Compounds
The optically active nitroalkenes 2 obtained by the rho-
dium-catalyzed asymmetric addition presented here should
be useful chiral building blocks since they should be readily
transformable into a wide variety of optically active com-
pounds 7 through organic reactions either at their electron-
deficient carbon–carbon double bonds or at the nitro
groups as mentioned in the preceding section, see Equation
(2).[1,3]
To indicate the versatile utility of nitroalkenes 2, Michael
addition of enantio-enriched 2i (98% ee) to methyl acrylate
in the presence of DBU as a base (Scheme 3) was first
tested, providing 7a in a high yield and with a maintained Figure 3. X-ray structure of 7a (CCDC-605923).
Scheme 4. Diastereoselective epoxidation of 2a to 7b (CCDC-605922).
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pound 7a underwent a rearrangement reaction to be trans- crystal structure analysis of 7b showed the phenyl group to
formed into 12, a promising precursor for the syntheses of be syn to the oxirane ring.
enones and corresponding acetates or carbonates, in 76%
Conjugated addition of phenylethynyllithium, prepared
yield with no loss of enantioselectivity.
in situ from phenylacetylene and n-butyllithium, to 2a in
Diastereoselective epoxidation of 2a with lithium tert-bu- THF at –78 °C over 24 h gave 7c as the sole diastereomer
tyl peroxide (tBuOOLi),[17] generated in situ from tert-butyl in 91% yield and with 98% ee (Scheme 5). The substituents
hydroperoxide and n-butyllithium in toluene at –78 °C, fur- at the three contiguous stereogenic centers are all cis on
nished 7b as the sole diastereomer in a good yield and with the basis of X-ray crystallographic analysis of 7c (Figure 4).
a high enantioselectivity of 96% ee (Scheme 4). The X-ray Reduction of 7c with a combined reagent consisting of zinc
powder and 2% HCl aqueous solution in ethanol at room
temperature generated 13 in 81% yield.
Michael addition of an enolate prepared in situ from
methyl acetate and lithium diisopropylamide (LDA) at
–78 °C to 2a furnished compound 14 (CCDC-605920) in
70% yield and in a high diastereomeric ratio of 12:1 in favor
of the cis,cis diastereomer, as determined by X-ray crystal-
lographic analysis (Scheme 6).
Total Synthesis of Optically Pure (+)-γ-Lycorane and (+)-
β-Lycorane
β- and γ-Lycorane are deoxygenated skeletons of Amar-
Scheme 5. Preparation of chiral amine 13 from 2a.
ylliaceae alkaloids.[18] The syntheses of these molecules have
received much attention from synthetic chemists because of
the challenging tetracyclic galanthan skeleton and their po-
tent biological activity.[19] Despite the apparent absence of
useful pharmaceutical properties, lycorane has become a
popular target for illustrating potential new strategies for
the synthesis of this family of alkaloids.
All of the ring junctures in γ-lycorane are cis[20] and total
syntheses of racemic γ-lycorane have been reported by se-
veral groups.[8] A number of efforts[9] geared towards asym-
metric syntheses of optically active (+)-γ-lycorane have also
been reported, but with only one example involving the
asymmetric catalytic construction of the stereogenic centers
(with 46% ee[9a]) a concise asymmetric catalytic total synthe-
sis of optically pure (+)-γ-lycorane is of great importance.
Asymmetric nitroallylation either of 3,4-methylenedioxy-
phenylboronic acid or of 3,4-methylenedioxyphenylzinc
chloride with 2-nitrocyclohex-2-enyl acetate (1a) was ap-
plied to a concise asymmetric total synthesis of (+)-γ-lycor-
ane (Scheme 7). Nitroallylation of 3,4-methylenedioxyphen-
Figure 4. X-ray structure of 7c (CCDC-605921).
ylboronic acid with 1a in the presence of 5 mol-% rhodium
Scheme 6. Diastereoselective Michael addition of an enolate to 2a.
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Asymmetric Nitroallylation of Arylmetallics
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complex of [Rh(OH)(COD)]2 and (S)-binap gave the prod- concise total synthesis of optically pure (+)-γ-lycorane from
uct 2i in 65% yield and with 98% ee (Table 2, Entry 9), the reaction between 1a and 3,4-methylenedioxyphenyl-
whilst the similar reaction with 3,4-methylenedioxyphenyl- boronic acid is 38%, and was improved to 52% when the
zinc chloride catalyzed by 3 mol-% rhodium complex of synthesis commenced with the reaction between 1a and 3,4-
Rh(acac)(C2H4)2 and (S)-binap afforded the product 2i in methylenedioxyphenylzinc chloride.
an improved yield of 89% yield and with an excellent
Efforts toward the total syntheses of racemic β-lycorane
enantioselectivity of 96% ee (Table 3, Entry 10). Treatment have been undertaken,[10] but in contrast, no asymmetric
of 2i with methyl acetate and lithium diisopropylamide synthesis of optically active (+)-β-lycorane has yet ap-
(LDA) at –78 °C furnished compound 15a in a high dia- peared, so such an asymmetric synthesis would be desirable.
stereomeric ratio of 7:1 in favor of the cis,cis diastereomer. The relative configuration between the aryl and the nitro
The cis,cis-15a was subjected to Raney nickel-catalyzed hy- groups in β-lycorane is trans, whilst that between aryl and
drogenation under 80 atmosphere of hydrogen at 55 °C, acetate is cis. (+)-β-Lycorane was also synthesized in the
which directly formed lactam 16a in 95% yield. A modified same way as (+)-γ-lycorane (Scheme 8), starting with the
Pictet–Spengler ring closure[21] of 16a with paraformalde- nitroallylation of 3,4-methylenedioxyphenylzinc chloride
hyde and trifluoroacetic acid afforded 17a in 88% yield, and with 1a in the presence of 3 mol-% rhodium complex of
reduction of 17a with lithium aluminum hydride gave (+)- Rh(acac)(C2H4)2 and (R)-binap to yield the product (R)-2i
γ-lycorane in 98% yield with an optical rotation consistent with 96% ee. Treatment of 2i with methyl acetate and lith-
with that of the natural product.[20] The overall yield of this ium diisopropylamide (LDA) at –78 °C furnished com-
Scheme 7. Highly enantioselective total synthesis of (+)-γ-lycorane.
Scheme 8. Total synthesis of optically pure (+)-β-lycorane.
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General Procedure for the Asymmetric Nitroallylation of Aryl-
boronic Acids with Nitroallyl Acetates Catalyzed by Chiral Rhodium
Complexes: Under argon, a solution of [Rh(OH)(COD)]2 (3.4 mg,
15 µmol, 5 mol-% Rh), (S)-binap (11.2 mg, 18 µmol, 6 mol-%) and
phenylboronic acid (183 mg, 1.5 mmol, 5 equiv.) in 1,4-dioxane
(1.0 mL) was stirred at 50 °C for 2 h. Then a solution of the cyclic
nitroallyl acetate (0.3 mmol) in 1,4-dioxane (1.0 mL) was added to
the reaction mixture, followed by addition of water (200 µL). The
reaction mixture was stirred at 50 °C for another 20 h. After evapo-
ration of the solvent, the residue was purified by column
pound 15b in a high diastereomeric ratio of 7:1 in favor of
the cis,cis diastereomer, treatment of 15b with DBU in
CH3CN at room temperature for 24 h provided a thermo-
dynamically stable diastereomer 15c in a quantitative yield,
and Raney nickel-catalyzed hydrogenation of 15c under 80
atmospheres of hydrogen at 55 °C proceeded to generate 18,
which was converted to 16b in an overall 95% yield by heat-
ing at reflux in toluene for 24 h. A Pictet–Spengler ring clo-
sure[21] of 16b with paraformaldehyde and trifluoroacetic
acid under conditions similar to those used for the synthesis chromatography on silica gel (diethyl ether/PET, 1:20).
of 17a provided 17b in 90% yield, and reduction of 17b
with lithium aluminum hydride in THF at reflux over 24 h
gave (+)-β-lycorane in 97% yield with an optical rotation
consistent with that of the natural product.[20] The overall
yield of this concise total synthesis of optically pure (+)-β-
lycorane from 1a is 53% (Scheme 8). It is worth noting that
this represents the first example of total synthesis of op-
tically pure β-lycorane.
1-Nitro-6-phenylcyclohexene (2a): Yield 34 mg, 56%; white solid,
m.p. 71.3–72.0 °C. [α]2D0 = +92.5 (c = 1.07, CHCl ). IR (KBr): ν =
˜
3
3456, 3023, 2946, 2920, 2867, 1663, 1510, 1491, 1451, 1413, 1333,
1
1077, 938 cm–1. H NMR (CDCl3, 300 MHz): δ = 1.55–1.62 (m, 2
H), 1.89–1.92 (m, 1 H), 2.01–2.03 (m, 1 H), 2.40–2.49 (m, 2 H),
4.29 (br. s, 1 H), 7.14–7.34 (m, 5 H), 7.57 (t, J = 4.0 Hz, 1 H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 16.5, 25.0,31.5, 39.5, 126.7, 127.1,
128.5, 136.2, 141.9, 150.9 ppm. HRMS: calcd. for C12H13NO2
203.0940, found 203.0928. C12H13NO2 (203.09): calcd. C 70.93, H
6.41, N 6.89; found C 70.84, H 6.44, N 6.84. Enantiomeric excess:
96%, detemined by chiral GC analysis [CP-Cyclodextrin-2,3,6-M-
19, 0.25 mm×25 m, column temperature 168 °C (isothermal), in-
ject temperature 240 °C, detector temperature 260 °C, inlet pressure
10 psi].
Conclusions
In conclusion, we have developed an enantioselective
rhodium-catalyzed nitroallylation of arylboronic acids and
organozinc reagents with nitroallyl acetates. This study
demonstrates that the rhodium complex of [Rh(OH)-
(COD)]2 and optically pure binap is an optimal catalyst,
providing high enantioselectivities ranging from 90–
99% ees for the nitroallylation of various arylboronic acids.
The rhodium complex of Rh(acac)(C2H4)2 and (R)-binap
shows high enantioselectivity and catalytic activity for the
nitroallylation of organozinc reagents. A number of chiral
synthetic intermediates have been readily prepared from the
products of the asymmetric nitroallylation. Concise total
syntheses of optically pure (+)-γ-lycorane in 38% overall
yield by starting with nitroallylation of arylboronic acids
with nitroallyl acetates and in an overall 52% yield by start-
ing with nitroallylation of organozinc reagents with nitroal-
lyl acetates have been accomplished and the first total syn-
thesis of optically pure (+)-β-lycorane was completed in an
overall yield of 53% commencing from the asymmetric ni-
troallylation of organozinc reagents with nitroallyl acetates.
Crystal Data of 2a: CCDC-289193, C12H13NO2 (203.23), ortho-
rhombic, space group P212121, a = 6.1206(5), b = 12.592(1), c =
14.007(1) Å, V = 1079.57(12) Å3, T = 290(2) K, Z = 4, Dcalcd.
=
1.250 mg/m3, µ = 0.085 mm–1, λ = 0.71073 Å, F(000) = 432, crystal
size 0.56×0.50×0.42 mm, 1483 reflections collected, 1380 [R(int)
= 0.0122]; refinement method: full-matrix least squares on F2;
goodness-of-fit on F2 = 0.961, final R indices [IϾ2σ(I)]: R1
0.0327, wR2 = 0.0652.
=
6-(4-Methylphenyl)-1-nitrocyclohexene (2b): Yield 41 mg, 63%,
white solid, m.p. 54.4–55.9 °C. [α]2D0 = +84.3 (c = 0.86, CHCl3). IR
1
(KBr): ν = 3447, 3022, 2950, 2872, 1660, 1506, 1336, 809 cm–1. H
˜
NMR (CDCl3, 300 MHz): δ = 1.57 (m, 2 H), 1.89 (m, 1 H), 2.00
(m, 1 H), 2.32 (s, 3 H), 2.39 (m, 2 H), 4.26 (br. s, 1 H), 7.04 (d, J
= 8.0 Hz, 2 H), 7.14 (d, J = 8.0 Hz, 2 H), 7.55 (t, J = 4.0 Hz, 1 H)
ppm. 13C NMR (CDCl3, 75 MHz): δ = 16.4, 20.8, 24.9, 31.5, 39.0,
126.9, 129.1, 135.9, 136.2, 138.8, 151.0 ppm. HRMS: calcd. for
C13H15NO2 217.1097, found 217.1095. Enantiomeric excess: 95%,
determined by chiral GC analysis [CP-Cyclodextrin-2,3,6-M-19,
0.25 mm×25 m, column temperature 168 °C (isothermal), inject
temperature 240 °C, detector temperature 260 °C, inlet pressure
10 psi].
6-(4-Methoxyphenyl)-1-nitrocyclohexene (2c): Yield 41 mg, 58%;
white solid, m.p. 56.8–57.9 °C. [α]2D0 = +93.4 (c = 1.06, CHCl3). IR
Experimental Section
(KBr): ν = 3494, 2996, 2859, 2936, 2833, 1658, 1613, 1507, 1460,
˜
1448, 1336, 1258, 1177, 1031, 823, 815 cm–1. 1H NMR (CDCl3,
300 MHz): δ = 1.54–1.61 (m, 2 H), 1.82–1.88 (m, 1 H), 1.96–2.00
(m, 1 H), 2.39–2.47 (m, 2 H), 3.77 (s, 3 H), 4.23 (br. s, 1 H), 6.81
(d, J = 11.5 Hz, 2 H), 7.04 (d, J = 11.5 Hz, 2 H), 7.52 (t, J = 4.0
Hz, 1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 16.5, 25.0, 31.6,
38.7, 55.2, 113.9, 128.1, 134.0, 135.8, 151.2, 158.3 ppm. HRMS:
calcd. for C13H15NO3 233.1046, found 233.1033. Enantiomeric ex-
cess: 95%, determined by chiral HPLC [Daicel Chiralpak OD; hex-
ane/2-propanol, 99:1; flow 1.0 mL/min; (R) isomer: tR = 12.4 min;
(S) isomer: tR = 14.5 min].
General Techniques: All manipulations were carried out under ar-
gon. NMR spectra were recorded with a Bruker 300-MHz spec-
trometer. Mass spectra were recorded with a VG 7070E instrument.
Elemental analysis was recorded with a Carlo Erba 1106 instru-
ment. HR-MS (ESI) spectra were recorded with a Bruker Bio-
TOF Q instrument. THF, toluene, and dioxane were dried with
sodium/benzophenone. Diethyl ether, petroleum ether (PET) and
ethyl acetate for column chromatography were distilled before use.
CCDC-289193 (2a), -605923 (7a), -605922 (7b), -605921 (7c),
-605920 (14) contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
6-(4-Chlorophenyl)-1-nitrocyclohexene (2d): Yield 45 mg, 64%; col-
orless oil. [α]2D0 = +102.2 (c = 1.15, CHCl ). IR (neat): ν = 2943,
˜
3
1
2867, 1662, 1517, 1488, 1336, 1091, 1013, 819. H NMR (CDCl3,
4100
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 4093–4105

Asymmetric Nitroallylation of Arylmetallics
FULL PAPER
300 MHz): δ = 1.25–1.62 (m, 2 H), 1.84–1.87 (m, 1 H), 2.03 (m, 1
1-Nitro-5-phenylcyclopentene (2j): Yield 23 mg, 40%, colorless oil.
H), 2.41–2.48 (m, 2 H), 4.24 (br. s, 1 H), 7.06 (d, J = 11.0 Hz, 2 [α]2D0 = +7.0 (c = 0.16, CHCl ). IR (KBr): ν = 2946, 1634, 1507,
˜
3
H), 7.24 (d, J = 11.0 Hz, 2 H), 7.56 (t, J = 4.0 Hz, 1 H) ppm. 13C 1359 cm–1; H NMR (CDCl3, 300 MHz): δ = 2.06–2.11 (m, 1 H),
1
NMR (CDCl3, 75 MHz): δ = 16.5, 24.9, 31.4, 39.0, 128.4, 128.7,
132.5, 136.6, 140.5, 150.5 ppm. HRMS calcd. for C12H12ClNO2 13C NMR (CDCl3, 75 MHz): δ = 29.5, 33.3, 47.9, 126.7, 127.0,
237.0551, found 237.0569. Enantiomeric excess: 99%, determined 128.8, 139.5, 142.0, 155.2 ppm. Enantiomeric excess: 17%, deter-
by chiral GC analysis [CP-Cyclodextrin-2,3,6-M-19, 0.25 mm×25 m, mined by chiral HPLC analysis [Daicel Chiralpak OD; hexane/2-
2.65–2.80 (m, 3 H), 4.36–4.40 (m, 1 H), 7.18–7.34 (m, 6 H) ppm.
column temperature 168 °C (isothermal), inject temperature
240 °C, detector temperature 260 °C, inlet pressure 10 psi].
propanol, 99:1; flow 1.0 mL/min; (R) isomer: tR = 10.71 min; (S)
isomer: tR = 12.34 min].
6-(4-Fluorophenyl)-1-nitrocyclohexene (2e): Yield 40 mg, 61%; col-
6-(3,4-Methylenedioxyphenyl)-1-nitrocyclohexene (2i): Yield 45 mg,
orless oil. [α]2D0 = +87.3 (c = 1.22, CHCl ). IR (neat): ν = 3069,
65%; colorless oil. [α]2D0 = +98.2 (c = 1.40, CHCl ). IR (neat): ν =
˜
˜
3
3
2945, 2868, 1662, 1602, 1509, 1336, 1222, 826, 816 cm–1. H NMR
2942, 2897, 1661, 1607, 1513, 1486, 1439, 1333, 1249, 1231, 1037,
1
(CDCl3, 300 MHz): δ = 1.52–1.61 (m, 2 H), 1.84–1.87 (m, 1 H), 934, 809 cm–1. H NMR (CDCl3, 300 MHz): δ = 1.55–1.62 (m, 2
1
2.02 (m, 1 H), 2.39–2.48 (m, 2 H), 4.26 (br. s, 1 H), 6.95–7.01 (m,
H), 1.81–1.87 (m, 1 H), 1.95–2.00 (m, 1 H), 2.38–2.47 (m, 2 H),
2 H), 7.10–7.13 (m, 2 H), 7.55 (t, J = 4.0 Hz, 1 H) ppm. 13C NMR 4.19 (br. s, 1 H), 5.92 (s, 2 H), 6.57–6.84 (m, 3 H), 7.52 (t, J = 4.0
(CDCl3, 75 MHz): δ = 16.4, 24.9, 31.5, 38.8, 115.1, 115.4, 128.5,
Hz, 1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 16.4, 24.9, 31.5,
128.6, 136.4, 137.7, 150.8, 160.0, 163.2 ppm. HRMS: calcd. for
39.1, 100.9, 107.7, 108.1, 120.0, 135.8, 136.1, 146.3, 147.774,
C12H12FNO2 221.0846, found 221.0834. Enantiomeric excess: 98%, 150.9 ppm. HRMS: calcd. for C13H13NO4 247.0839, found
determined by chiral GC analysis [CP-Cyclodextrin-2,3,6-M-19,
0.25 mm×25 m, column temperature 168 °C (isothermal), inject
temperature 240 °C, detector temperature 260 °C, inlet pressure
10 psi].
247.0852. Enantiomeric excess: 98%, determined by chiral HPLC
analysis [Daicel Chiralpak OD; hexane/2-propanol, 99:1; flow
1.0 mL/min; (R) isomer: tR = 15.3 min; (S) isomer: tR = 21.5 min].
6-(3-Methylphenyl)-1-nitrocyclohexene (2k): Yield 88%; colorless
6-(4-tert-Butylphenyl)-1-nitrocyclohexene (2f): Yield 52 mg, 67%;
white solid, m.p. 82.0–83.5 °C. [α]2D0 = +98.2 (c = 0.70, CHCl3). IR
oil. [α]2D0 = –80.7 (c = 0.14, CHCl ). IR (neat): ν = 2942, 1660,
˜
3
1513, 1339 cm–1. H NMR (CDCl3, 300 MHz): δ = 1.56–1.60 (m,
1
(KBr): ν = 2958, 2865, 1659, 1513, 1342, 1330, 1075, 1018,
2 H), 1.85–1.90 (m, 1 H), 1.98–2.02 (m, 1 H), 2.31 (s, 3 H), 2.39–
˜
823 cm–1. 1H NMR (CDCl3, 300 MHz): δ = 1.28 (s, 9 H), 1.57– 2.48 (m, 2 H), 4.25 (br. s, 1 H), 7.02–7.26 (m, 4 H), 7.53 (t, J = 4.0
1.86 (m, 2 H), 1.87–2.02 (m, 2 H), 2.40–2.48 (m, 2 H), 4.25 (br. s,
1 H), 7.04 (d, J = 8.3 Hz, 2 H), 7.28 (d, J = 8.3 Hz, 2 H), 7.53 (t,
J = 4.0 Hz, 1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 16.6,
24.9, 31.2, 31.4, 34.3, 39.0, 125.3, 126.7, 135.8, 138.7, 149.3, 149.3,
151.1 ppm. HRMS: calcd. for C16H21NO2 259.1567, found
259.1554. Enantiomeric excess: 90%, determined by chiral GC
analysis [CP-Cyclodextrin-2,3,6-M-19, 0.25 mm×25 m, column
temperature 168 °C (isothermal), inject temperature 240 °C, detec-
tor temperature 260 °C, inlet pressure 10 psi].
Hz, 1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 16.5, 20.9, 25.0,
31.6, 39.1, 127.0, 129.2, 136.0, 136.3, 138.9, 151.1 ppm. Enantio-
meric excess: 85%, determined by Chiral GC analysis [CP-Cyclo-
dextrin-2,3,6-M-19, 0.25 mm×25 m, column temperature = 168 °C
(isothermal), inject temperature 240 °C, detector temperature
260 °C, inlet pressure 10 psi].
General Procedure for the Asymmetric Nitroallylation of the Orga-
nometallic Reagent with Nitroallyl Acetates Catalyzed by Chiral
Rhodium Complexes: Under argon, ArZnCl (0.30 mmol; in THF)
was added dropwise to a stirred solution of Rh(acac)(C2H4)2
(1.6 mg, 15 µmol, 3 mol-%) (R)-BINAP (4.1 mg, 18 µmol,
3.3 mol%) and substrate 1a (37.4 mg, 0.20 mmol) in THF (1.0 mL)
1-Nitro-6-(4-trifluoromethylphenyl)cyclohexene (2g): Yield 42 mg,
52%; colorless oil. [α]2D0 = +107.2 (c = 0.83, CHCl ). IR (neat): ν
˜
3
= 2943, 2871, 1664, 1618, 1519, 1325, 1163, 1112, 1066, 1017 cm–1.
1H NMR (CDCl3, 300 MHz): δ = 1.52–1.63 (m, 2 H), 1.87–1.90 at 0 °C. After the mixture had been stirred at 0 °C for 20 h, the
(m, 1 H), 2.08 (m, 1 H), 2.44–2.52 (m, 2 H), 4.32 (br. s, 1 H), 7.25 reaction was quenched with water (50 µL). After evaporation of the
(d, J = 8.2 Hz, 2 H), 7.55 (d, J = 8.2 Hz, 2 H), 7.62 (t, J = 4.0 Hz, solvent, the residue was purified by column chromatography on
1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 16.5, 24.9, 31.4, 39.5,
122.2, 125.5, 127.4, 128.4, 128.9, 129.3, 129.4, 137.0, 146.1,
150.2 ppm. HRMS: calcd. for C13H12F3NO2 271.0814, found
271.0808. Enantiomeric excess: 94%, determined by chiral GC
analysis [CP-Cyclodextrin-2,3,6-M-19, 0.25 mm×25 m, column
temperature 168 °C (isothermal), inject temperature 240 °C, detec-
tor temperature 260 °C, inlet pressure 10 psi].
silica (diethyl ether/PET, 1:20) to yield 2.
4-[6-(3,4-Methylenedioxyphenyl)-1-nitrocyclohex-2-enyl]butan-2-one
(7a): A solution of 1-nitrocyclohexene (2i) (110 mg, 0.44 mmol),
methyl acrylate (0.08 mL, 0.88 mmol) and DBU (7.0 µL,
0.04 mmol) in acetonitrile (1.0 mL) was stirred at room tempera-
ture for 3 h. The acetonitrile was evaporated under reduced pres-
sure. The crude product was purified by flash chromatography
(PET/EA, 5:1) to give 7a (140 mg, 96%) as a white solid; m.p.
6-(3-Methoxyphenyl)-1-nitrocyclohexene (2h): Yield 41 mg, 58%;
white solid, m.p. 81.7–83.6 °C. [α]2D0 = +108.5 (c = 1.29, CHCl3).
113.4–114.5 °C. [α]2D0 = –148.6 (c = 0.64, CHCl ). IR (KBr): ν =
˜
3
IR (KBr): ν = 2942, 2866, 2835, 1662, 1600, 1583, 1515, 1487, 1330,
2947, 2891, 1739, 1535, 1489, 1441, 1352, 1265, 1203 cm–1. 1H
˜
1285, 1263, 1042, 781 cm–1. 1H NMR (CDCl3, 300 MHz): δ = 1.57– NMR (CDCl3, 300 MHz): δ = 1.68 (m, 1 H), 2.21–2.35 (m, 5 H),
1.62 (m, 2 H), 1.88–1.93 (m, 1 H), 1.98–2.17 (m, 1 H), 2.40–2.48
2.40–2.51 (m, 2 H), 3.04 (m, 1 H), 3.66 (s, 3 H), 5.84 (d, J = 10.2
(m, 2 H), 3.78 (s, 3 H), 4.24 (br. s, 1 H), 6.68 (s, 1 H), 6.72–6.78 Hz, 1 H), 5.90 (s, 2 H), 6.24 (m, 1 H), 6.57 (d, J = 7.56 Hz, 1 H),
(m, 2 H), 7.19 (m, 1 H), 7.55 (d, J = 8.2 Hz, 2 H), 7.62 (t, J = 4.0
6.60 (s, 1 H), 6.69 (d, J = 7.56 Hz, 1 H) ppm. 13C NMR (CDCl3,
Hz, 1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 16.6, 25.0, 31.4, 75 MHz): δ = 24.2, 24.8, 28.8, 33.0, 47.6, 51.8, 91.3, 100.9, 108.0,
39.5, 55.1, 111.6, 113.4, 119.5, 129.5, 136.2, 143.6, 150.8, 108.1, 121.4, 123.9, 132.6, 135.0, 146.9, 147.6, 172.5 ppm. HRMS:
159.7 ppm. HRMS: calcd. for C13H15NO3 233.1046, found
233.1055. Enantiomeric excess: 96%, determined by chiral HPLC
analysis [Daicel Chiralpak OD; hexane/2-propanol, 99:1; flow
1.0 mL/min; (R) isomer: tR = 22.5 min; (S) isomer: tR = 25.3 min].
calcd. for C17H19NNaO6 [M + Na]+ 356.1105, found 356.1121. En-
antiomeric excess: 98%, determined by chiral HPLC analysis
[Daicel Chiralpak AS; hexane/2-propanol, 7:3; flow 1.0 mL/min;
(R) isomer: tR = 11.90 min; (S) isomer: tR = 14.55 min].
Eur. J. Org. Chem. 2006, 4093–4105
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4101

L. Dong, Y.-J. Xu, W.-C. Yuan, X. Cui, L.-F. Cun, L.-Z. Gong
FULL PAPER
Crystal Data of 7a: CCDC-605923, C17H19NO6 (333.33), mono-
clinic, space group P2(1), a = 9.102(2), b = 7.185(1), c =
perature for 24 h, the reaction was quenched with a saturated aque-
ous NH4Cl solution (10 mL). The organic layer was separated and
12.243(2) Å, β = 96.02°, V = 796.22(24) Å3, T = 296(2) K, Z = 2, the aqueous layer was extracted with ethyl acetate (3×10 mL). The
Dcalcd. = 1.390 mg/m3, µ = 0.106 mm–1, λ = 0.71073 Å, F(000) =
352, crystal size: 0.52×0.52×0.26 mm, 2443 reflections collected,
2220 [R(int) = 0.0154]; refinement method: full-matrix least squares
on F2; goodness-of-fit on F2 = 0.999, final R indices [IϾ2σ(I)]: R1
= 0.0369, wR2 = 0.0881.
combined organic layers were washed with brine and dried with
anhydrous sodium sulfate. After removal of the solvent under re-
duced pressure, the residue was purified by flash chromatography
(PET/EA, 20:1) to give 7c (138 mg, 91%) as a white solid; m.p.
130.9–132.0 °C. [α]2D0 = –83.3 (c = 0.72, CHCl ). IR (KBr): ν =
˜
3
2936, 2955, 2866, 1596, 1545, 1489, 1441, 1375, 1346, 1242 cm–1.
1H NMR (CDCl3, 300 MHz): δ = 1.51 (m, 1 H), 1.82 –1.83 (m, 1
H), 2.05–2.11 (m, 1 H), 2.16- 2.17 (m, 1 H), 2.32–2.38 (m, 1 H),
2.51–2.57 (m, 1 H), 3.01–3.12 (m, 2 H), 5.10 (t, J = 4.20 Hz, 1 H),
7.19–7.36 (m, 10 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 23.4,
24.8, 26.2, 33.7, 45.6, 83.7, 86.7, 90.3, 122.5, 127.1, 127.7, 128.1,
128.2, 128.8, 131.7, 139.5 ppm. HRMS: calcd. for C20H19NNaO2
[M + Na]+ 328.1308, found 328.1319. Enantiomeric excess: 98%,
determined by chiral HPLC analysis [Daicel Chiralpak AS; hexane/
2-propanol, 85:15; flow 1.0 mL/min; (R) isomer: tR = 7.48 min; (S)
isomer: tR = 8.43 min].
4-[3-Hydroxy-6-(3,4-methylenedioxyphenyl)cyclohex-1-enyl]butan-2-
one (12): A solution of DABCO (70 mg, 0.62 mmol) and 7a
(136 mg, 0.41 mmol) in 1,2-dichlorobenzene (2.0 mL) was refluxed
for 30 min, then the solvent was removed under reduced pressure.
The crude product was purified by flash chromatography (PET/
EA, 1:1) to give 12 (95 mg, 76%) as colorless oil. [α]2D0 = –65.8 (c
= 0.36, CHCl ). IR (neat): ν = 3408, 2934, 1733, 1483, 1435, 1264,
˜
3
1229 cm–1. H NMR (CDCl3, 300 MHz): δ = 1.53 (m, 1 H), 1.70–
1
1.73 (m, 2 H), 1.90–1.91 (m, 2 H), 2.12- 2.20 (m, 2 H), 2.32–2.41
(m, 2 H), 3.21 (m, 1 H), 3.61 (s, 3 H), 4.25 (br. s, 1 H), 5.70 (br. s,
1 H), 5.91 (s, 2 H), 6.61–6.73 (m, 3 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 28.0, 29.5, 30.2, 32.1, 43.9, 51.5, 66.3, 100.8, 108.0,
108.6, 121.3, 127.2, 137.5, 140.8, 145.9, 147.6, 173.4 ppm. HRMS:
calcd. for C17H20NNaO5 [M + Na]+ 327.1203, found 327.1215. En-
antiomeric excess: 98%, determined by chiral HPLC analysis
[Daicel Chiralpak OD; hexane/2-propanol, 90:10; flow 1.0 mL/min;
(R) isomer: tR = 11.70 min; (S) isomer: tR = 14.88 min].
Crystal Data of 7c: CCDC-605921, C20H19NO2 (205.36), triclinic,
¯
space group P1, a = 10.054(2), b = 11.932(2), c = 14.177(3) Å, α =
99.36°, β = 100.40°, γ = 90.29°, V = 1649.40(47) Å3, T = 296(2) K,
Z = 4, Dcalcd. = 1.230 mg/m3, µ = 0.079 mm–1, λ = 0.71073 Å,
F(000) = 648, crystal size: 0.64×0.64×0.20 mm, 6711 reflections
collected, 6126 [R(int) = 0.0105]; refinement method: full-matrix
least squares on F2; goodness-of-fit on F2 = 0.947, final R indices
[IϾ2σ(I)]: R1 = 0.0384, wR2 = 0.0900.
1-Nitro-2-phenyl-7-oxabicyclo[4.1.0]heptane (7b): nBuLi (1.57 mL,
2.52 mmol, 1.6  in hexanes) was added to a solution of tBuOOH
(0.5 mL, 2.52 mmol, 5.0–6.0 ) in toluene (5.0 mL) at –78 °C. To
the mixture was added dropwise a solution of 2a (170 mg,
0.84 mmol) in toluene (1.0 mL) at –78 °C. After the mixture had
been stirred for 8 h at this temperature, the reaction was quenched
with an aq. saturated NH4Cl solution (10 mL). The organic layer
was separated, and the aqueous layer was extracted with ethyl ace-
tate (3×10 mL). The combined organic layers were washed with
10% aq. Na2SO3 solution (10 mL) and brine and dried with anhy-
drous sodium sulfate. After the solvent had been removed under
reduced pressure, the residue was purified by flash chromatography
using (PET/EA, 20:1) to give 7b (123 mg, 67%) as a white solid;
2-Phenyl-6-(phenylethynyl)cyclohexylamine (13): 2% HCl (2.0 mL)
and Zn powder (102 mg, 1.58 mmol) were added to a solution of
7c (135 mg, 0.45 mmol) in EtOH (10 mL) at room temperature. Af-
ter being stirred for 1 d, the mixture was filtered and concentrated.
The filtrate was diluted with AcOEt (10 mL), and then washed with
saturated aqueous NaHCO3 (10 mL) and brine (10 mL). After re-
moval of the solvent, the residue was purified by column
chromatography on silica gel to give 13 (99.5 mg, 81% yield) as
white solid; m.p. 65.8–67.8 °C. [α]2D0 = –53.6 (c = 0.39, CHCl3). IR
1
(KBr): ν = 2929, 2854, 1596, 1488, 1440 cm–1. H NMR (CDCl ,
˜
3
300 MHz): δ = 1.11 (br. s, 2 H), 1.25 (m, 1 H), 1.42–1.47 (m, 1 H),
1.61–1.97 (m, 3 H), 2.11–2.17 (m, 1 H), 2.78–2.2.83 (m, 1 H), 2.89–
2.92 (m, 1 H), 3.47 (t, J = 2.82 Hz, 1 H), 7.23–7.40 (m, 10 H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 22.6, 25.6, 25.8, 36.7, 47.1, 54.0,
82.1, 92.0, 123.5, 126.3, 127.5, 127.6, 128.1, 128.3, 131.5,
143.9 ppm. HRMS: calcd. for C20H22N [M + H]+ 276.1747, found
276.1740.
m.p. 93.7–95.1 °C. [α]2D0 = +50.0 (c = 0.80, CHCl ). IR (KBr): ν =
˜
3
2944, 2929, 1538, 1493, 1362, 1270 cm–1. 1H NMR (CDCl3,
300 MHz): δ = 1.60–1.68 (m, 1 H), 1.74–1.78 (m, 1 H), 1.89–1.98
(m, 2 H), 2.17–2.23 (m, 1 H), 3.61 (d, J = 4.90 Hz, 1 H), 4.07 (m,
1 H), 7.23–7.39 (m, 5 H) ppm. 13C NMR (CDCl3, 75 MHz): δ =
20.5, 23.0, 29.3, 41.7, 58.8, 89.1, 127.6, 128.1, 128.7, 138.6 ppm.
HRMS: calcd. for C12H13NO3 [M + H]+ 242.0895, found 242.1172.
Enantiomeric excess: 96%, determined by chiral HPLC analysis
[Daicel Chiralpak AD; hexane/2-propanol, 99:1; flow 1.0 mL/min;
(R) isomer: tR = 9.86 min; (S) isomer: tR = 11.28 min].
Methyl 2-(2-Nitro-3-phenylcyclohex-1-yl)acetate (14): A solution of
2a (121 mg, 0.6 mmol) in THF (3.0 mL) was added to the lithium
enolate, which was prepared in situ from AcOMe (3.3 mmol), diiso-
propylamide (3.3 mmol), and nBuLi (3.3 mmol, 2.2  in hexane)
at –78 °C within 20 min. After stirring at –78 °C for 3 h, a solution
of AcOH (0.4 mL) in THF (3.0 mL) was added, and the mixture
was warmed to –40 °C within 20 min. After usual workup and puri-
fication by column chromatography on silica gel (AcOEt/PET,
1:15), compound 14 was obtained. Yield: 70%; diastereomeric ratio
of 12:1 in favor of cis,cis derivative was determined by 1H NMR
spectroscopy. Physical property and characterization of the major
Crystal Data of 7b: CCDC-605922, C12H13NO3 (219.23), mono-
clinic, space group P2(1)/c, a = 5.754(1), b = 26.725(4), c =
7.623(1) Å, β = 108.061°, V = 1079.57(12) Å3, T = 296(2) K, Z =
4, Dcalcd. = 1.307 mg/m3, µ = 0.094 mm–1, λ = 0.71073 Å, F(000) =
464, crystal size: 0.58×0.40×0.26 mm, 2423 reflections collected,
2070 [R(int) = 0.0107]; refinement method: full-matrix least squares
on F2; goodness-of-fit on F2 = 1.056, final R indices [IϾ2σ(I)]: R1
= 0.0392, wR2 = 0.1067.
product: m.p. 106.8–108.7 °C. IR (KBr): ν = 3452, 2951, 2937,
˜
2864, 1727, 1544, 1273 cm–1. 1H NMR (CDCl3, 300 MHz): δ =
1.56–1.67 (m, 2 H), 1.76–1.84 (m, 2 H), 2.06 (m, 1 H), 2.29–2.32
(m, 2 H), 2.49–2.54 (m, 2 H), 3.04–3.08 (m, 1 H), 3.68 (s, 3 H),
5.04 (t, J = 4.0 Hz, 1 H), 7.18–7.25 (m, 2 H), 7.27–7.33 (m, 3 H)
ppm. 13C NMR (CDCl3, 75 MHz): δ = 23.6, 24.9, 25.3, 36.7, 36.9,
45.7, 51.8, 90.9, 127.1, 127.4, 128.6, 139.8, 171.9 ppm. HRMS:
calcd. for C15H19NO4 277.1308, found 277.1291.
[2-Nitro-3-(phenylethynyl)cyclohexyl]benzene (7c): nBuLi (0.94 mL,
1.5 mmol, 1.6  in hexanes) was added to a solution of phenyl-
acetylene (0.18 mL, 1.5 mmol) in THF (3.0 mL) at –78 °C, and
then the mixture was stirred at 0 °C for 3 h. A solution of 2a
(101 mg, 0.5 mmol) in THF (1.0 mL) was added dropwise to the
mixture at –78 °C. After the mixture had been stirred at this tem-
4102
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 4093–4105

Asymmetric Nitroallylation of Arylmetallics
FULL PAPER
Crystal Data of 14: CCDC-605920, C15H19NO4 (277.31), mono-
clinic, space group P2(1)/c, a = 9.955(2), b = 10.050(2), c =
15.080(3) Å, β = 107.27°, V = 1440.61(46) Å3, T = 293(2) K, Z =
(CDCl3, 75 MHz): δ = 24.2, 27.5, 35.1, 40.2, 43.7, 58.8, 101.0,
107.5, 108.5, 119.7, 136.2, 146.4, 148.0, 177.9 ppm. HRMS: calcd.
for C15H17NO3 259.1203, found 259.1203. Enantiomeric excess:
4, Dcalcd. = 1.279 mg/m3, µ = 0.093 mm–1, λ = 0.71073 Å, F(000) = 98%, determined by chiral HPLC [Daicel Chiralpak OJ-H; hexane/
592, crystal size: 0.58×0.38×0.38 mm, 3140 reflections collected,
2682 [R(int) = 0.0105]; refinement method: full-matrix least squares
on F2; goodness-of-fit on F2 = 0.949, final R indices [IϾ2σ(I)]: R1
= 0.0360, wR2 = 0.0865.
2-propanol, 70:30; flow 1.0 mL/min; (R) isomer: tR = 8.1 min; (S)
isomer: tR = 13.3 min].
(3aS,7R,7aS)-7-(Benzo[1,3]dioxol-5-yl)octahydroindol-2-one (16b):
To a solution of 15b (96 mg, 0.3 mmol) in absolute ethanol
(1.0 mL) in an autoclave was added Raney nickel (5 mol%) pre-
Methyl [3-c-(1,3-Benzodioxol-5-yl)-2-c-nitrocyclohex-1-r-yl]acetate
(15a): A solution of (S)-2i (121 mg, 0.6 mmol) in THF (3.0 mL) viously rinsed with absolute ethanol. Hydrogen was introduced into
was added to the lithium enolate, which was prepared in situ from
AcOMe (3.3 mmol), diisopropylamide (3.3 mmol), and nBuLi
(3.3 mmol, 2.2  in hexane) at –78 °C within 20 min. After the mix-
ture had been stirred at –78 °C for 3 h, a solution of AcOH
(0.4 mL) in THF (3.0 mL) was added and the mixture was warmed
to –40 °C within 20 min. After usual workup and purification by a
column chromatography on silica gel (AcOEt/PET, 1:15), com-
pound 15a was obtained (138 mg, 72% yield) as colorless oil. A
diastereomeric ratio of 7:1 in favor of the cis,cis derivative was de-
the autoclave until the pressure reached 80 atm. The autoclave was
warmed to 55 °C and was maintained at the temperature for 24 h.
After the autoclave was cooled to room temperature, the mixture
was filtered, the filtrate was concentrated, and then refluxed in tol-
uene (5.0 mL) for 24 h. Recrystallization from CHCl3/hexane gave
16b (74 mg, 95 % yield) as a white solid; m.p. 201.7–202.5 °C.
[α]2D0 = +78.6 (c = 0.70, CHCl ). IR (KBr): ν = 3442, 3214, 2932,
˜
3
2855, 1688, 1499, 1487, 1443, 1239, 1228, 1036 cm–1
.
1H NMR
(CDCl3, 300 MHz): δ = 1.40–1.57 (m, 3 H), 1.90–1.93 (m, 3 H),
2.03–2.15 (m, 2 H), 2.33 (m, 1 H), 2.54 (m, 1 H), 3.11 (t, J = 10.0
termined by 1H NMR. IR (KBr): ν = 2939, 2864, 1733, 1543, 1504,
˜
1
1440 cm–1. H NMR (CDCl3, 300 MHz): δ = 1.48–1.78 (m, 4 H), Hz, 1 H), 5.31 (br. s, 1 H), 5.93 (s, 2 H), 6.61–6.67 (m, 2 H), 6.72–
2.03 (m, 1 H), 2.28 (m, 2 H), 2.39- 2.45 (m, 2 H), 2.45–2.99 (m, 1
6.76 (m, 1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 26.0, 28.1,
H), 3.68 (s, 3 H), 4.98 (t, J = 4.0 Hz, 1 H), 5.91 (s, 2 H), 6.63 – 32.9, 37.9, 44.8, 48.4, 65.3, 100.9, 106.9, 108.4, 119.9, 136.1, 146.4,
6.71 (m, 2 H), 6.74 (d, J = 8.1 Hz, 1 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 24.1, 24.9, 25.3, 36.7, 36.9, 45.5, 51.8, 91.1, 101.0,
107.6, 108.3, 120.4, 133.7, 146.7,147.8, 171.8 ppm. HRMS: calcd.
for C16H19NO6 321.1207, found 321.1206.
148.0, 177.6 ppm. HRMS: calcd. for C15H17NNaO3 [M + Na]+
282.1101, found 282.1109.
(3aR,12bS,12cS)-2,3,3a,4,12b,12c-Hexahydro-1H,7H-[1,3]dioxolo-
[4,5-j]pyrrolo[3,2,1-de]phenanthridin-5-one (17a): To a solution of
Methyl [3-c-(1,3-Benzodioxol-5-yl)-2-t-nitrocyclohex-1-r-yl]acetate 16a (52 mg, 0.20 mmol) in anhydrous Cl(CH2)2Cl (5.0 mL) were
(15c): A solution of 15b (96 mg, 0.3 mmol) and DBU (0.004 mL,
0.03 mmol) in acetonitrile (5.0 mL) was stirred at room tempera-
ture for 24 h. The acetonitrile was evaporated under reduced pres-
sure. The crude product was purified by column chromatography
on silica gel (AcOEt/PET, 1:10) to give compound 15c (96 mg,
Ͼ99% yield) as a white solid; m.p. 93.2–94.1 °C. [α]2D0 = +60.8 (c
added sequentially paraformaldehyde (23.1 mg, 0.77 mmol) and
CF3CO2H (0.19 mL, 2.5 mmol) at room temperature. The mixture
was stirred at room temperature for 24 h, and then the reaction
was quenched with a saturated aqueous NaHCO3 solution
(10 mL), followed by addition of CH2Cl2 (40 mL). The organic
layer was separated and the aqueous phase was extracted with ethyl
acetate. The combined organic layers were washed with brine and
= 0.74, CHCl ). IR (KBr): ν = 2938, 2862, 1737, 1548, 1487, 1440,
˜
3
1368, 1274 cm–1. H NMR (CDCl3, 300 MHz): δ = 1.32 (m, 1 H), dried with Na2SO4. After removal of the solvent under reduced
1
1.51–1.62 (m, 2 H), 1.84–1.86 (m, 1 H), 1.98–2.03 (m, 2 H), 2.19–
2.28 (m, 2 H), 2.34–2.40 (m, 1 H), 3.06–3.10 (m, 1 H), 3.67 (s, 3
pressure, the residue was purified by column chromatography on
silica gel (AcOEt/PET, 3:1) to give 17a (47 mg, 88% yield) as a
H), 4.45 (t, J = 11.0 Hz, 1 H), 5.90 (s, 2 H), 6.59–6.71 (m, 3 H) white solid; m.p. 144.0–147.7 °C. IR (KBr): ν = 2927, 2854, 1676,
˜
ppm. 13C NMR (CDCl3, 75 MHz): δ = 24.7, 30.0, 32.8, 36.8, 38.6,
48.3, 51.7, 95.3, 101.0, 107.2, 108.4, 120.5, 133.8, 146.8, 147.8,
171.3 ppm. HRMS: calcd. for C16H19NNaO6 [M + Na]+ 344.1105,
found 344.1102. Enantiomeric excess: 97%, determined by chiral
HPLC analysis [Daicel Chiralpak OD; hexane/2-propanol, 80:20;
1503, 1483, 1440, 1418 cm–1. 1H NMR (CDCl3, 300 MHz): δ =
1.12 –1.32 (m, 3 H), 1.68 (m, 3 H), 2.04 (d, J = 16.0 Hz, 1 H), 2.39
(m, 1 H), 2.51 (dd, J = 16.0 Hz, 6.8 Hz, 1 H), 2.69 (m, 1 H), 3.73
(t, J = 4.5 Hz, 1 H), 3.76 (d, J = 17.3 Hz, 1 H), 4.49 (d, J = 17.3
Hz, 1 H), 5.89 (m, 2 H), 6.57 (s, 1 H), 6.59 (s, 1 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 23.5, 27.8, 30.2, 32.9, 39.7, 40.2, 42.6, 55.6,
100.9, 106.6, 108.4, 123.2, 131.5, 146.5, 146.6, 175.6 ppm.
HRMS:calcd. for C16H17NO3 271.1203, found 271.1193.
flow 1.0 mL/min; (R) isomer: tR = 8.54 min; (S) isomer: tR
=
9.80 min].
(3aR,7S,7aS)-7-(Benzo[1,3]dioxol-5-yl)octahydroindol-2-one (16a):
To a solution of 15a (96 mg, 0.3 mmol) in absolute ethanol
(1.0 mL) in an autoclave was added Raney nickel (5 mol%) pre-
viously rinsed with absolute ethanol. Hydrogen was introduced into
the autoclave until the pressure reached 80 atm. The autoclave was
warmed to 55 °C and maintained at that temperature for 24 h. Af-
ter the autoclave was cooled to room temperature, the mixture was
filtered and the filtrate was concentrated. Recrystallization from
CHCl3/hexane gave 16a (74 mg, 95% yield) as a white solid; m.p.
(3aS,12bR,12cS)-2,3,3a,4,12b,12c-Hexahydro-1H,7H-[1,3]dioxolo-
[4,5-j]pyrrolo[3,2,1-de]phenanthridin-5-one (17b): To a solution of
16b (52 mg, 0.20 mmol) in anhydrous Cl(CH2)2Cl (5.0 mL) were
added sequentially paraformaldehyde (23.1 mg, 0.77 mmol) and
CF3CO2H (0.19 mL, 2.5 mmol) at room temperature. The mixture
was stirred at room temperature for 24 h, and then the reaction
was quenched with
a saturated aqueous NaHCO3 solution
(10 mL), followed by addition of CH2Cl2 (40 mL). The organic
layer was separated, and the aqueous phase was extracted with
ethyl acetate. The combined layers were washed with brine and
185.9–187.2 °C. [α]2D0 = +112.3 (c = 1.30, CHCl ). IR (KBr): ν =
˜
3
3252, 2927, 2915, 2853, 1681, 1502, 1488, 1242, 1230, 1039 cm–1.
1H NMR (CDCl3, 300 MHz): δ = 1.25–1.33 (m, 2 H), 1.68–1.75 dried with anhydrous sodium sulfate. After removal of the solvent
(m, 3 H), 1.82 (m, 1 H), 1.96 (d, J = 16.0 Hz, 1 H), 2.47 (m, 1 H),
2.52 (m, 1 H), 2.78–2.82 (m, 1 H), 3.84 (t, J = 4.2 Hz, 1 H), 5.33
(br. s, 1 H), 5.95 (s, 2 H), 6.63 (d, J = 1.5 Hz, 1 H), 6.66 (dd, J =
1.5 Hz, 7.9 Hz, 1 H), 6.75 (d, J = 7.9 Hz, 1 H) ppm. 13C NMR
under reduced pressure, the residue was purified by column
chromatography on silica gel (AcOEt/PET, 3:1) to give 17b (49 mg,
90% yield) a white solid; m.p. 212.2–213.1 °C. [α]2D0 = +184.1 (c =
0.44, CHCl ). IR (KBr): ν = 2932, 2859, 1680, 1502, 1487,
˜
3
Eur. J. Org. Chem. 2006, 4093–4105
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4103

L. Dong, Y.-J. Xu, W.-C. Yuan, X. Cui, L.-F. Cun, L.-Z. Gong
FULL PAPER
1411 cm–1. H NMR (CDCl3, 300 MHz): δ = 1.34–1.40 (m, 2 H),
1
[4]
For examples of catalytic asymmetric 1,4-addition to nitroal-
kenes, see a) H. Brunner, B. Kimel, Monatsh. Chem. 1996, 127,
1063–1072; b) N. Sewald, V. Wendisch, Tetrahedron: Asym-
metry 1998, 9, 1341–1344; c) J. P. G. Versleijen, A. M.
van Leusen, B. L. Feringa, Tetrahedron Lett. 1999, 40, 5803–
5806.
T. Hayashi, T. Senda, M. Ogasawara, J. Am. Chem. Soc. 2000,
122, 10716–10717.
For preliminary results: L. Dong, Y.-J. Xu, L.-F. Cun, X. Cui,
A.-Q. Mi, Y.-Z. Jiang, L.-Z. Gong, Org. Lett. 2005, 7, 4285–
4288.
1.68 (m, 1 H), 1.92–1.99 (m, 3 H), 2.00 (m, 1 H), 2.43–2.50 (m, 3
H), 2.68 (m, 1 H), 4.37 (d, J = 3.83 Hz, 2 H), 5.92 (s, 2 H), 6.58
(s, 1 H), 6.70 (s, 1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 25.8,
27.8, 27.8, 38.3, 40.5, 42.9, 42.9, 64.7, 101.0, 104.8, 107.3, 125.1,
130.6, 146.2, 146.7, 175.0 ppm. HRMS: calcd. for C16H17NNaO3
[M + Na]+ 294.1101, found 294.1089. Enantiomeric excess: 98%,
determined by chiral HPLC analysis [Daicel Chiralcel AD; hexane/
2-propanol, 85:15; flow 1.0 mL/min; (R) isomer: tR = 12.35 min;
(S) isomer: tR = 14.45 min].
[5]
[6]
(+)-γ-Lycorane (8): A mixture of 17a (40 mg, 0.15 mmol) and Li-
AlH4 (17.1 mg, 0.45 mmol) in THF (5.0 mL) was stirred at reflux
for 18 h, then Na2SO4 was added. The precipitate was removed by
filtration and washed with diethyl ether (10 mL×3). The combined
solutions were concentrated, and the residue was purified by flash
column chromatography (Et2O) to give (+)-γ-lycorane (37 mg, 98%
yield) as colorless oil. [α]2D0 = +17.3 (c = 0.98, EtOH) {ref.[20] [α]2D0
[7]
a) T. Hayashi, R. Shintani, H. Doi, J. Am. Chem. Soc. 2004,
126, 6240–6241. For a review on the copper-catalyzed asym-
metric 1,4-addition reactions of alkylzinc reagents, see: b) K.
Tomioka, Y. Nagaoka, in: Comprehensive Asymmetric Catalysis
(Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamatomo), Springer, New
York, 1999; chapter 31.1.
[8]
For total syntheses of racemic γ-lycorane, see: a) N. Ueda, T.
Tokuyama, T. Sakan, Bull. Chem. Soc. Jpn. 1966, 39, 2012; b)
H. Irie, Y. Nishitani, M. Sugita, S. Uyeo, J. Chem. Soc. C 1970,
1313; c) 9b; d) B. Genem, Tetrahedron Lett. 1971, 12, 4105–
4108; e) H. Hara, O. Hoshino, B. Umezawa, Tetrahedron Lett.
1972, 13, 5031–5034; f) B. Umezawa, O. Hoshino, S. Sawaki,
S. Sato, N. Numao, J. Org. Chem. 1977, 42, 4272–4275; g) H.
Iida, Y. Yuasa, C. Kibayashi, J. Am. Chem. Soc. 1978, 100,
3598–3599; h) H. Iida, Y. Yuasa, C. Kibayashi, J. Org. Chem.
1979, 44, 1074–1080; i) H. Higashiyama, T. Honda, H. Otom-
asu, T. Kametani, Planta Med. 1983, 48, 268; j) N. Sugiyama,
M. Narimiya, H. Iida, T. Kibuchi, J. Heterocycl. Chem. 1988,
25, 1455; k) J. E. Bäckvall, P. G. Andersson, G. B. Stone, A.
Gogoll, J. Org. Chem. 1991, 56, 2988–2993; l) W. H. Pearson,
J. M. Sckeryantz, J. Org. Chem. 1992, 57, 6783–6789; m) D. B.
Grotjahn, P. C. Vollhardt, Synthesis 1993, 579–605; n) M. G.
Banwell, A. W. Wu, J. Chem. Soc., Perkin Trans. 1 1994, 2671–
2672; o) S. R. Angle, J. P. Boyce, Tetrahedron Lett. 1995, 36,
6185–6188; p) M. Ikeda, S. Ohtani, T. Sato, H. Ishibashi, Syn-
thesis 1998, 1803–1806; q) X. Huang-Cong, B. Quiclet-Sire,
S. Z. Zard, Tetrahedron Lett. 1999, 40, 2125–2126; r) A. Padwa,
M. A. Brodney, S. M. Lynch, J. Org. Chem. 2001, 66, 1716–
1724; s) O. Tamura, H. Matsukida, A. Toyao, Y. Takeda, H.
Ishibashi, J. Org. Chem. 2002, 67, 5537–5545; t) Z. Shao, J.
Chen, R. Huang, C. Wang, L. Li, H. Zhang, Synlett 2003,
2228–2230; u) T. Yasuhara, E. Osafune, K. Nishimura, M. Ya-
mashita, K.-i. Yamada, O. Muraoka, K. Tomioka, Tetrahedron
Lett. 2004, 45, 3043–3045.
= +17.1 (c = 0.25, EtOH)}. IR (KBr): ν = 2928, 2848, 1505, 1483,
˜
1375, 1318, 1245, 1226, 1038 cm–1; 1H NMR (CDCl3, 300 MHz):
δ = 1.25–1.35 (m, 5 H), 1.42 (m, 3 H), 1.69–2.20 (m, 3 H), 2.36 (t,
J = 4.5 Hz, 1 H), 2.70 (m, 1 H), 3.18 (d, J = 14.4 Hz, 1 H), 3.23
(m, 1 H), 3.99 (d, J = 14.4 Hz, 1 H), 5.87 (m, 2 H), 6.49 (s, 1 H),
6.61 (s, 1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 25.2, 29.2,
30.3, 31.7, 37.3, 39.4, 53.7, 57.1, 62.8, 100.6, 106.2, 108.3, 127.3,
133.1, 145.6, 146.0 ppm. HRMS: calcd. for C16H20NO2 [M + H]+
258.1489, found 258.1496. The spectroscopic data are in agreement
with those reported in the literature.[20]
(+)-β-Lycorane (9): A mixture of 17b (40 mg, 0.15 mmol) and Li-
AlH4 (17.1 mg, 0.45 mmol) in THF (5.0 mL) was stirred at reflux
for 24 h, then Na2SO4 was added. The precipitate was removed by
filtration and washed with diethyl ether (10 mL×3). The filtrate
was concentrated, and the residue was purified by flash column
chromatography (Et2O) to give (+)-β-lycorane (36 mg, 97% yield)
as colorless oil. [α]2D0 = +142.5 (c = 0.17, EtOH) {ref.[20] [α]2D0
=
+143.3 (c = 1.04, EtOH)}. IR (KBr): ν = 2928, 2845, 1724,
˜
1
1483 cm–1. H NMR (CDCl3, 300 MHz): δ = 1.13–1.17 (m, 2 H),
1.50–1.54 (m, 4 H), 1.93–1.98 (m, 2 H), 2.23- 2.34 (m, 2 H), 2.45–
2.52 (m, 1 H), 3.31- 3.41 (m, 2 H), 4.04 (d, J = 14.2 Hz, 1 H), 3.23
(m, 1 H), 5.87 (dd, J = 1.41 Hz, 4.71 Hz, 2 H), 6.50 (s, 1 H), 6.71
(s, 1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 26.4, 28.2, 28.8,
30.1, 41.7, 42.9, 53.8, 57.3, 71.9, 100.6, 105.3, 106.8, 128.5, 131.2,
145.6, 146.1 ppm. HRMS: calcd. for C16H20NO2 [M + H]+
258.1489, found 258.1482.
[9]
For total syntheses of optically active (+)-γ-lycorane, see: a) H.
Yoshizaki, H. Satoh, Y. Sato, S. Nukui, M. Shibasaki, M.
Mori, J. Org. Chem. 1995, 60, 2016–2021; b) J. Cossy, L. Tres-
nard, D. G. Pard, Eur. J. Org. Chem. 1999, 1925–1933; c) M. G.
Banwell, J. E. Harvey, D. C. Hockless, J. Org. Chem. 2000, 65,
4241–4250.
Acknowledgments
[10]
For total syntheses of racemic β-lycorane, see: a) K. Kotera,
Tetrahedron 1961, 12, 240–247; b) R. K. Hill, J. A. Joule, L. J.
Loerrler, J. Am. Chem. Soc. 1962, 84, 4951–4956; c) H. Tanaka,
Y. Nagai, H. Irie, S. Uyeo, A. Kuno, J. Chem. Soc., Perkin
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S. H. Simonsen, J. Org. Chem. 1982, 47, 3634–3643; e) K. To-
mioka, T. Yasuhara, K. Nishimura, M. Yamashita, N. Fukuy-
ama, K. I. Yamada, O. Muraoka, Org. Lett. 2003, 5, 1123–
1126.
K. Yoshida, M. Ogasawara, T. Hayashi, J. Am. Chem. Soc.
2002, 124, 10984–10985.
W.-C. Yuan, L.-F. Cun, L.-Z. Gong, A.-Q. Mi, Y.-Z. Jiang,
Tetrahedron Lett. 2005, 46, 509–512.
P. W. N. M. van Leeuwen, P. C. J. Kamer, J. N. H. Reek, P. Di-
We are grateful for financial support from the National Natural
Science Foundation of China (Grants 203900505 and 20325211).
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4104
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 4093–4105

Asymmetric Nitroallylation of Arylmetallics
FULL PAPER
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Received: March 29, 2006
Published Online: July 24, 2006
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Eur. J. Org. Chem. 2006, 4093–4105
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