Enantioselective synthesis of functionalized nitrocyclopropanes by organocatalytic conjugate addition of bromonitroalkanes to α,β- unsaturated enones

Article abstract of DOI:10.1002/chem.200801651

A general enantioselective synthesis of functionalized nitrocyclopropanes by organocatalytic conjugate addition of a variety of bromonitroalkanes to α,β-unsaturated enone systems is presented. The process, efficiently catalyzed by the salts of 9amino-9-de

Full text of DOI:10.1002/chem.200801651

DOI: 10.1002/chem.200801651
Enantioselective Synthesis of Functionalized Nitrocyclopropanes by
Organocatalytic Conjugate Addition of Bromonitroalkanes to a,b-
Unsaturated Enones
Jian Lv, Jiaming Zhang, Zhu Lin, and Yongmei Wang*[a]
Abstract: A general enantioselective
synthesis of functionalized nitrocyclo-
propanes by organocatalytic conjugate
addition of a variety of bromonitroal-
kanes to a,b-unsaturated enone sys-
tems is presented. The process, effi-
ciently catalyzed by the salts of 9-
amino-9-deoxyepiquinine 1d serves as
a powerful approach to the preparation
of synthetically and biologically impor-
tant cyclopropanes with high levels of
enantio- and diastereoselectivities.
Since only 0.6 equivalents of bromoni-
tromethane are used as a reagent, (S)-
2e is obtained enantiomerically pure
by employing chiral 1d as a highly effi-
cient catalyst for its kinetic resolution
(97% ee at 51% conversion, selectivity
s=120).
Keywords: asymmetric catalysis
·
enones · Michael addition · nitrocy-
clopropanes · organocatalysis
Introduction
pressive degrees of enantioselectivity by using a very simple
procedure.
With representation in more than 4000 natural isolates[1] and
100 biologically active agents, the cyclopropane framework
has long been established as an attractive target for medici-
nal chemistry. In this regard, the development of effective
asymmetric entries to cyclopropane architecture constitutes
an important research field. The current available methods
for the synthesis of cyclopropanes include intensively stud-
ied organometallic-based catalysis[2–4] and asymmetric ver-
sions of the Simmons–Smith reaction.[5] Notably, recently
Gaunt pioneered the use of ammonium ylides in enantiose-
lective intermolecular[6] and intramolecular[7] cyclopropana-
tion by using cinchona alkaloids as organocatalysts. More-
over, Kojima and Ohkata have used cinchonidine as a chiral
Brønsted base for the asymmetric cyclopropanation reaction
between chloromethyl ketones and b-substituted methylide-
nemalononitriles.[8] Furthermore, the advent in the most
recent years of enantioselective cyclopropanation of a,b-un-
saturated aldehydes catalyzed by chiral imidazolidinones,
pioneered by MacMillan et al.,[9] and improved by Arvids-
son,[10] Cꢀrdova,[11] and Wang,[12] allowed us to obtain im-
In particular, the recent confirmation of the first biologi-
cally active natural product structure to contain a chiral ni-
trocyclopropane moiety[13] prompted us to undertake the de-
velopment of a convenient, organocatalytic Michael-based
route to functionalized nitrocyclopropanes of high potential
synthetic utility. For example, a diastereoselective nitrocy-
clopropanation has been reported by Ballini et al.[14] Nota-
bly, Ley and co-workers reported the first organocatalytic
nitrocyclopropanation of cyclohexenone by using their pro-
line tetrazole catalyst with modest yields and enantioselec-
tivities,[15] and Arai and co-workers reported an asymmetric
cyclopropane reaction of a-bromocyclopentenone with ni-
tromethane by using quaternary ammonium salts as the
phase-transfer catalysts.[16] Moreover, Connon and co-works
have used cinchona alkaloids derivatives as catalysts for the
asymmetric cyclopropanation of nitroalkenes with modest
enantioselectivities.[17]
Herein, we report the highly enantioselective catalytic
asymmetric reaction between bromonitroalkanes and a,b-
unsaturated enones that gives the corresponding nitrocyclo-
propanes in high yields and with excellent asymmetric in-
duction (up to >99% ee). In particular, the successful appli-
cation of new primary amine salts as iminium catalysts for
enone substrates has rarely been explored.[18]
[a] Dr. J. Lv, Dr. J. Zhang, Dr. Z. Lin, Prof. Dr. Y. Wang
Department of Chemistry
Key Laboratory of Elemento-Organic Chemistry
Nankai University, 97 Weijin Road
Tianjin, 300071 (China)
Fax : (+86)22-2350-2654
E-mail: ymw@nankai.edu.cn
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Chem. Eur. J. 2009, 15, 972 – 979

FULL PAPER
Results and Discussion
Subsequently, we found that 9-amino-9-deoxyepiquinine 1d
exhibited much higher catalytic activity, and the product
4aa was obtained in 82% yield with 90% ee after 12 h at
room temperature (Table 1, entry 5). Compounds 1e and 1 f
furnished comparable yields and enantioselectivities
(Table 1, entries 6 and 7). A variety of solvents were
screened; however, inferior results to that with 1d were ob-
served (Table 1, entries 8–15). The product 4aa was formed
with the best yield and enantioselectivity when the reaction
was conducted in the solvent system PhCH3/CH2Cl2 (v/v,
7:3) at room temperature (Table 1, entry 16). The yield and
enantioselectivity of this reaction was decreased at 08C
(Table 1, entry 17). Notably, the use of the benzoic acid salt
of the easily available 9-amino-9-deoxyepiquinine 1d, which
was very recently described as an effective catalyst for
enone activation,[20] afforded a promising yield and stereoin-
duction. With this consideration in mind, a survey of various
salts of the chiral primary amine 1d were performed
(Table 1, entry 17).
The proposed organocatalytic nitrocyclopropanation strat-
egy was first examined by reacting cyclohexenone 2a with
bromonitromethane (3a) in the presence of a series of chiral
amines as the catalysts (Table 1). We found that the addition
of one equivalent of NMM was crucial to obtain high yields.
Interesting, secondary amines, such as proline (Table 1,
entry 1), afforded poor results. As the relative bulkiness of
secondary amines might be unfavorable for the formation of
iminium ions with a,b-unsaturated ketones, we questioned
whether primary amines, owing to their reduced steric re-
quirements, might be suitable for enone activation.[19]
Preliminary studies confirmed that the primary amines
1a–c were able to promote the reaction with moderate cata-
lytic efficiency and enantioselectivity (Table 1, entries 2–4).
Table 1. Catalyst screen for the reaction between 2a and 3a.[a]
An extensive screening of the acidic additives revealed
that the use of N-Boc phenylalanine gave the product 4aa
with a high yield (96–98%; Table 2, entries 5–7) and high
enantiomeric excess (97% ee, Table 2, entries 5–7). Surpris-
ingly, employing the racemic or enantiomeric counterion
formed the same enantiomeric product 4aa with very similar
selectivity; thus, we didnꢂt consider that the chiral anion of
the amine salt of 1d might influence asymmetric induction.
Table 2. Acid Additive screen for the reaction between 2a and 3a.[a]
Entry
Additive
Yield [%][b]
ee [%][c]
1
2
3
4
AcOH
80
86
87
95
99
92
89
95
Entry
Catalyst
Solvent
t [h]
Yield [%][b]
ee [%][c]
TFA[d]
1
2
3
4
5
6
7
8
proline
1a
1b
1c
1d
1e
1 f
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
THF
PhCH3
CH3OH
H2O
DMSO
Et2O
24
14
12
24
12
12
12
48
15
12
5
40
52
55
49
82
80
83
–
70
85
90
70
–
À35
66
31
75
90
89
À88
–
81
91
65
8
TsOH[d]
PhCOOH
5
6
7
96
98
96
97
97
97
9
10
11
12
13
14
15
16
17[e]
18[f]
6
48
18
16
12
24
12
–
8
9
R=CH3, PG=H[d]
R=Ph, PG=H[d]
87
96
92
93
94
99
95
92
97
93
95
92
98
96
60
54
90
60
95
46
73
94
84
95
nBu2O
10
11
12
13
14
R=3-Cl-Ph, PG=H[d]
R=3,5-F2-Ph, PG=H[d]
R=4-Br-Ph, PG=H[d]
R=4-CH3, PG=H[d]
R=Ph, PG=Ac[d]
[d]
[d]
[d]
PhCH3/CH2Cl2
PhCH3/CH2Cl2
PhCH3/CH2Cl2
[a] Reaction conditions: unless otherwise noted, 2a (0.3 mmol), 3a
(0.25 mmol), NMM (0.25 mmol), and catalyst (20 mol%) in the solvent
(0.5 mL) were stirred at room temperature for the time given. [b] Yield
of isolated product. [c] Determined by HPLC analysis. [d] PhCH3/CH2Cl2
(v/v, 7:3). [e] The reaction was performed at 08C. [f] PhCOOH
(20 mol%) as acid additive.
[a] Reaction conditions: 2a (0.3 mmol), 3a (0.25 mmol), NMM
(0.25 mmol), 1d (20 mol%), and acid additive (20 mol%) in PhCH3/
CH2Cl2 (7:3) were stirred at room temperature for 12 h. [b] Yield of iso-
lated product. [c] Determined by HPLC analysis. [d] PG=protecting
group; TFA=trifluoroacetic acid; Ts=tosyl.
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973

Y. Wang et al.
Table 4. Scope of the organocatalytic cyclic enones nitropropanation.[a]
Next, we evaluated the efficiency of catalytic salts derived
from the combination of 1d with a series of (rac)-mandelic
acids (Table 2, entries 9–14). Variation in the electronic con-
tribution of substituents on the phenyl ring reveals that the
electron-donating methyl group engenders higher yields
(99%) and enantioselectivities (98% ee). The presence of a
protecting group in the hydroxy acid had a little deleterious
effect on the catalytic activity (Table 2, entry 14). On the
basis of these studies, (rac)-4-methyl mandelic acid was
chosen for further investigations as it proved to be superior
with regard to enantioselectivity and catalytic efficiency.
Next, we examined the nitrocyclopropanation of a range
of bromonitro compounds 3 to cyclohexenone 2a under the
optimized conditions. Alkyl groups tested were suitable sub-
strates for the reaction and gave excellent enantioselectivi-
ties (Table 3, entries 1 and 2, ꢀ97%). However, phenyl
group compound 3c did not react with 2a, presumably
owing to the electronic effect.
Entry
Product
t [h]
Yield [%][b]
ee [%][c]
1
12
99
98
2
24
94
83
3
4
16
12
85
94
99
>99
Table 3. Nitrocyclopropanation of various bromonitroalkanes to cyclo-
hexenone.[a]
5[d,e]
48
83
>99
[a] Reaction conditions: 2a (0.3 mmol), 3a (0.25 mmol), NMM
(0.25 mmol), 1d (20 mol%), and p-methyl mandelic acid (20 mol%) in
PhCH3/CH2Cl2 (7:3) were stirred at room temperature. [b] Yield of isolat-
ed product. [c] Determined by HPLC analysis. [d] Structure deduced
from 1H NMR spectroscopic analysis (NOE). [e] Reaction condition: 2e
(0.3 mmol), 3a (0.18 mmol), NMM (0.18 mmol), 1d (20 mol%), and p-
methyl mandelic acid (20 mol%) in PhCH3/CH2Cl2 (7:3) were stirred at
room temperature.
Entry
R
Product
t [h]
Yield [%][b]
ee [%][c]
1
H
CH3
Ph
4aa
4ab[d]
–
12
48
72
99
54
–
98
97
–
2[d]
3
[a] Reaction conditions: 2a (0.3 mmol),
3
(0.25 mmol), NMM
(0.25 mmol), 1d (20 mol%), and p-methyl mandelic acid (20 mol%) in
PhCH3/CH2Cl2 (7:3) were stirred at room temperature. [b] Yield of isolat-
ed product. [c] Determined by HPLC analysis. [d] Structure deduced
nitrocyclopropanation as shown in Scheme 1. By using the
salt of 1d (20 mol%) and bromonitromethane (0.6 equiv) in
PhCH3/CH2Cl2 (v/v, 7:3) at room temperature for the resolu-
tion of (Æ)-4-tert-amyl-2-cyclohexenone (2e) on an 1 mmol
scale, an ee of 97% was reached at 51% conversion, which
indicated a selectivity (s) of 120 (Table 5, entry 1). A bulky
tert-butyl group (2 f) led to a slight decrease in the selectivi-
ty (s=61, Table 5, entry 2), and substrate 2g containing a
phenyl group at the 4-position also gave a lower selectivity
(s=7, Table 5, entry 3) than 2e. Unfortunately, substrate 2h
containing a relatively small methyl group at the 4-position
produced no selectivity.
1
from H NMR spectroscopic analysis (NOE).
Next, the scope of organocatalytic cyclic enone substitu-
ent nitrocyclopropanation was explored by using the stan-
dard reaction conditions and is reported in Table 4. It ap-
pears from these results that the enantioselectivity is depen-
dent on the ring size. For cyclopentenone 2b, the reaction
proceeds well giving a 94% yield of 4ba; however, the en-
antiomeric excess of the product was only 83% ee (Table 4,
entry 2). It is notable that increasing the ring size to seven-
membered rings led to an improvement in the enantioselec-
tivity up to 99% (Table 4, entry 3). For the six-membered
ring systems, it was pleasing to find that as well as the
known compound 2a, other substituted 2-cyclohexenones
were also formed with similarly high enantioselectivity
(Table 4, entries 4 and 5). Interestingly, the racemic enone
2e only gave one isomer and higher enantioselectivity (up
to >99% ee). 4-Alkyl-substituted 2-cyclohexenones may
provide high selectivity in the kinetic resolution of these
compounds.
To check the viability of the approach, we tested 1d in
the kinetic resolution of racemic 4-substituted 2-cyclohexe-
nones 2e–h under the conditions typical for the asymmetric
Scheme 1. Kinetic resolution of racemic 4-substituted 2-cyclohexenones
2e–h under conditions typical for asymmetric nitrocyclopropanation.
NMM=N-methyl morpholine.
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Chem. Eur. J. 2009, 15, 972 – 979

Synthesis of Functionalized Nitrocyclopropanes
FULL PAPER
Table 5. Kinetic resolution of 4-substituted 2-cyclohexenones 2e–h ac-
cording to Scheme 1.
unsatisfactory from an asymmetric catalysis standpoint: of
the additives tested DBU furnished 1d in racemic form,
whereas substoichiometric amounts of NMM as the base re-
sulted in a good enantioselectivity (95% ee), but diminished
yield (8%). Compound 1d was not involved catalytically in
this reaction.
To circumvent these difficulties, route B was examined
(Scheme 4). The initial Michael addition of bromonitrome-
thane 3a to 8a was promoted by chiral catalysts, with a sub-
Entry
Enone
t [h]
Conv. [%][a]
ee [%][b]
s
Conf.[c]
1
2
3
4
2e
2 f
2g
2h
24
24
24
12
51
54
58
60
97
99
76
–
120
61
8
S
S
S
–
–
[a] Yield of isolated product. [b] Determined by HPLC analysis. [c] Con-
figuration of the unconverted enone.
Based on the absolute and relative configuration of nitro-
cyclopropane derivatives 4, we propose the following mech-
anism to account for the organocatalytic nitrocyclopropana-
tion reaction of enones 2 (Scheme 2). We propose that a cin-
Scheme 4. Route B.
sequent amine-promoted ring-closure (Scheme 4). First, the
proposed organocatalytic Michael addition reaction was ex-
amined by reacting chalcone 8a with bromonitromethane
3a in the presence of 1d as the catalyst. The results of these
experiments are outlined in Table 6. We were pleased to
Table 6. Enantioselective Michael addition reaction with 1d.[a]
Entry
Acid
Yield [%][b]
d.r.[c]
ee [%][d,e]
1
2
-
50
85
82
87
78
85
80
84
85
99
1.7
1.6
1.6
1.4
1.5
1.5
1.6
1.6
1.2
1.2
85
98
95
99
93
97
98
98
p-methylmandelic acid
p-methylmandelic acid
TFA
3[f]
4
Scheme 2. A proposed catalytic cycle for the reaction of 2a and 3a with
cinchona alkaloid 1d.
5
6
7
8
AcOH
PhCOOH
N-Boc-benzyl l-glycine[g]
(R)-mandelic acid
TFA
chona alkaloid derivative, such as 1d, could render the nu-
cleophilic addition of the bromomethane 3a to the iminium
intermediate 5 enantioselective. Presumably, owing to steric
crash and multipoint binding interactions between the chiral
enamine intermediate 6 and the covalently linked cinchona
alkaloid, the rotational freedom of the chiral enamine
should be hampered. Next, the generated chiral enamine in-
termediate undergoes intramolecular 3-exo-tert nucleophilic
attack to form the cyclopropane ring 7. Hydrolysis of imini-
um intermediate 7 releases the catalyst and gives the nitro-
cyclopropane 4aa.
9[h]
10[i]
À97
TFA
>99
[a] Unless noted, reactions were carried out with 8a (0.15 mmol) and 3a
(0.125 mmol) in 0.5 mL of CHCl3 for 48 h. [b] Yield of isolated product.
[c] Determined by NMR analysis. [d] Determined by HPLC analysis.
[e] Enantiomeric excess for major isomer. [f] PhCH3:CH2Cl2 (v/v=7:3) as
solvent. [g] Boc=tert-butoxycarbonyl. [h] 1 f as an organocatalyst. [i] Re-
action was carried out with 8a (0.25 mmol) and 3a (0.125 mmol) in
0.5 mL of CHCl3 for 24 h.
The addition of 3a to chalcone 8a promoted by the salt of
organocatalyst 1d and Brønsted-base additives was then at-
tempted (Scheme 3). These experiments exposed route A as
find that 9-amino-9-deoxyepiquinine 1d in combination with
TFA (20 mol%) exhibited high bifunctional catalytic activi-
ty[21] for asymmetric Michael addition of 3a to chalcone 8a
in CHCl3 at room temperature (Table 6, entry 4). The enan-
tioselectivity was decreased in the presence of other acidic
additives (Table 6, entries 2 and 5–8). Under the optimized
conditions, 1 f furnished a comparable yield and enantiose-
lectivity (Table 6, entry 9). Moreover, it was necessary to
use two equivalents of chalcone 8a to obtain a good yield of
product (Table 6, entries 4 and 10).
Scheme 3. Route A. Base=none: no reaction; morpholine: 30% yield,
0% ee; NMM: 8% yield, 95% ee; DBU: 95% yield, 0% ee.
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Y. Wang et al.
Table 7. Effect of base and solvent on nitrocyclopropane stereochemis-
try.[a]
After considerable experimentation, it was found that the
variation of the bases had a substantial impact on diastereo-
selectivity, but
a minimal impact on enantioselectivity
(Table 7). The diastereoselectivity of the reaction was also
sensitive to the choice of organic base (Table 7, entries 1–7).
For example, when the reaction was performed in CH2Cl2
by using trans-dimethylpiperazine as the base, a slower but
cleaner reaction resulted, leading to the formation of the de-
sired product in a 94:6 diastereomeric ratio (d.r.) (Table 7,
entry 7). On closer examination of the reaction solvent,
CH2Cl2 was found to be the optimal solvent in terms of both
yield and distereoselection. However, the diastereoselectiv-
ity decreased in CHCl3, THF, PhCH3, and CH3OH (Table 7,
entries 8–11).
To investigate the scope of the present nitrocyclopropane
transformations, the reaction of 3a with a series of aromatic
(E)-a,b-unsaturated enones was explored under the opti-
mized reaction conditions (Table 8). It was pleasing to find
that these also worked very well and the nitrocyclopropane
adducts were all formed in high yields and with generally
excellent enantioselectivities. Electron-withdrawing (Cl,
CF3; Table 8, entries 13 and 15) substituents can be intro-
duced on the aromatic ring of R1 with a loss in diastereose-
lectivity; however, a recrystallization takes the 60:40 d.r. up
to 96:4 (Table 8, entry 15). Moreover, we were encouraged
to develop a one-pot cyclopropanation involving the con-
trolled 1d-catalyzed addition of
Entry
Solvent
Base
Yield
[%][b]
d.r.
9a/10a[c]
1
2
3
4
5
6
7
8
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
THF
morpholine
NMM
25
8
68:32
80:20
78:22
38:62
86:14
84:16
94:6
90:10
84:16
86:14
32:68
pyridine
80
95
50
75
71
65
75
72
80
DBU[d]
Et3N
nPr2NH
trans-2,5-dimethylpiperazine
trans-2,5-dimethylpiperazine
trans-2,5-dimethylpiperazine
trans-2,5-dimethylpiperazine
trans-2,5-dimethylpiperazine
9
10
11
PhCH3
CH3OH
[a] NMR spectroscopic data of 9a and 10a are consistent with the refer-
ence reported.[22] [b] Yield of isolated product. [c] Determined by NMR
spectroscopic analysis. [d] DBU=1,8-diazabicycloACHTNUTRGNEUNG[5.4.0]undec-7-ene.
Conclusion
In summary, a general enantioselective synthesis of function-
alized nitrocyclopropanes by organocatalytic conjugate addi-
bromonitromethane to (E)-a,b-
Table 8. Organocatalytic asymmetric Michael ring-closure reactions of 5a–j and 3a.
unsaturated enones, followed
by trans-dimethylpiperazine-
mediated cyclization. However,
enantioselectivity and diaste-
reoselectivity were decreased.
Work is now underway to ex-
plore the scope of the reaction
for the other substrates. Pre-
liminary indications suggest
that for the b-methyl with alter-
native groups, the Michael ad-
dition product was easily
formed in high yield and with
Entry
R1
Ph
Ph
R2
Yield [%][a]
Major product
d.r.[b] 9/10
ee [%][c,d]
1
70
75
66
70
75
76
63
67
73
70
60
61
77
80
85
82
80
71
76
72
94:6
90:10
95:5
85:15
96:4
90:10
90:10
87:13
>99
95
98
96
99
95
99
90
93
88
98
91
Ph
9a
9b
2[e]
3
4-Cl-C6H4
4[e]
5
Ph
3-Cl-C6H4
4-Me-C6H4
4-NO2-C6H4
3-furyl
Ph
9c
9d
9e
9 f
6[e]
7
excellent
enantioselectivity
Ph
8[e]
9
(98% ee); however, few nitro-
cyclopropane adducts were ob-
tained with trans-2,5-dimethyl-
piperazine as the base. Unfortu-
nately, oct-3-en-2-one as a Mi-
chael acceptor did not react
with 3a. These results suggest
that further optimization and
catalyst development will be
necessary to discover a general
nitrocyclopropanation
99:1
95:5
92:8
Ph
10[e]
11
Ph
12[e]
13
86:14
69:31 (99:1)[g]
85:15
60:40 (96:4)[g]
78:22
95:5
85:15
87:13
81:19
97 (>99)[f]
4-Cl-C6H4
4-CF3-C6H4
4-MeO-C6H4
2-naphthyl
9g
9h
14[e]
15
82
>99 (>99)[f]
Ph
16[e]
17[g]
18[e,g]
19
90
98
90
96
71
9i
9j
Ph
Ph
20[e]
ACHTUNGTRENNUNGprocedure.
[a] Yield of isolated product. [b] Determined by NMR spectroscopic analysis. [c] Determined by HPLC analy-
sis. [d] Enantiomeric excess for major isomer. [e] The one-pot reaction was carried out with 1a (0.13 mmol),
2a (0.125 mmol), 1d (20 mol%), and TFA (20 mol%). trans-Dimethylpiperazine (1.2 equiv) was added to the
mixture after 72 h. [f] After recrystallization. [g] trans-Dimethylpiperazine (2 equiv).
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Chem. Eur. J. 2009, 15, 972 – 979

Synthesis of Functionalized Nitrocyclopropanes
FULL PAPER
ACHUTNGRENU(NG 1R,6S,7R)-7-Nitro-5,5-dimethylbicycloACHTUNTGREN[NUGN 4.1.0]heptan-2-one (4da): The
tion of a variety of bromonitroalkanes to a,b-unsaturated
enone systems has been developed. The reaction is efficient-
ly catalyzed by the salt of cinchona alkaloid 1d. Cyclic and
aromatic enones can be used and the reaction with bromoni-
tromethane 3a provides the nitrocyclopropane products in
high yields with good to excellent stereoselectivities. Since
only 0.6 equivalents of bromomethane are used as a reagent,
(S)-2e is obtained enantiomerically pure by employing
chiral 1d as a highly efficient catalyst for their kinetic reso-
lution (97% ee at 51% conversion, selectivity s=120).
title compound was obtained according to the general procedure. White
solid; yield: 94%; [a]D20 =À134.6 (c=0.5 in CH2Cl2); 1H NMR (400 MHz,
ACTHNUTRGNEUNG
CDCl3, 258C, TMS): d=4.65 (t, 3J(H,H)=2.8 Hz, 1H), 2.82 (dd, 3J-
ACHUTNGRENNUG CAHTUNGTRENNUGN
(H,H)=1.9, 9.6 Hz, 1H), 2.40 (d, 3J(H,H)=9.5 Hz, 1H), 2.26 (dd, 3J-
AHCTUNGERTG(NNUN H,H)=4.6, 9.2 Hz, 2H), 1.41–1.53 (m, 2H), 1.12 (s, 3H), 1.19 ppm (s,
3H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=208.8, 54.6, 36.4, 32.9,
28.9, 26.8, 25.5, 24.2 ppm; MS (EI): m/z: 183 [M]+; HRMS-EI: m/z: calcd
for C7H9NO3: 183.08954; found: 183.08913 [M]+; HPLC (Chiralpak AD-
H, hexane/iPrOH 97:3, flow rate=0.6 mLminÀ1): t
(major)=25.5 min.
(1R,5R,6S,7R)-7-Nitro-5-tert-amylbicycloCATHNUGTRNEN[UG 4.1.0]heptan-2-one (4ea): The
RACHTUNGTREN(NUNG minor)=23.6, tR-
AHCTUNGTRENNUNG
title compound was obtained according to the general procedure. White
solid; yield: 83%; [a]D20 =+26.9 (c=0.5 in CH2Cl2); 1H NMR (400 MHz,
ACTHNUTRGNEUNG
CDCl3, 258C, TMS): d=4.51 (t, 3J(H,H)=3.2 Hz, 1H), 2.71 (d, 3J-
A
ACHTUNGTRNE(NUNG H,H)=3.2, 10.1 Hz, 1H), 2.41 (d,
Experimental Section
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
General: Commercial reagents were used as received, unless otherwise
stated. Catalysts 1d, 1e, and 1 f were synthesized according to literature
13C NMR (100 MHz, CDCl3, 258C, TMS): d=208.3, 62.0, 42.8, 38.7, 36.3,
34.4, 32.8, 32.6, 31.4, 24.3, 24.1, 7.8 ppm; MS (EI): m/z: 225 [M]+;
HRMS-EI: m/z: calcd for C7H9NO3: 225.13649 [M]+; found: 225.13605;
HPLC (Chiralpak AD-H, hexane/iPrOH 98:2, flow rate=0.5 mLminÀ1):
procedures.[21a] 1H and 13C NMR spectra were recorded on either
a
Bruker-DPX 300 or AV-400 sepectrometer. Chemical shifts are reported
in ppm from tetramethylsilane with the solvent resonance as the internal
standard. Accurate mass data were obtained on VG ZAB-HS by EI. Op-
tical rotations were measured on a Perkin–Elmer 341 Polarimeter at
208C. HPLC analysis was performed on Shimadzu CTO-10AS by using a
Chiralpak AD-H and OD-H column purchased from Daicel Chemical
t CHTUGTNRNENUG(minor)=24.0, tRACHTUNGTRENNUNG
RA
(major)=35.8 min.
G
[4.1.0]heptan-2-one (4ab): The title
compound was obtained according to the general procedure. White solid;
yield: 54%; [a]2D0 =À40.1 (c=0.5 in CH2Cl2); H NMR (400 MHz, CDCl3,
1
258C, TMS): d=2.70–2.80 (m, 2H), 2.37–2.44 (m, 1H), 2.22–2.31 (m,
1H), 2.11–2.02 (m, 1H), 1.85–1.93 (m, 2H), 1.78 (s, 3H), 1.59–1.65 ppm
(m, 1H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=203.2, 69.8, 39.0,
35.6, 23.6, 18.0, 12.8 ppm; MS (EI): m/z: 169 [M]+; HRMS-EI: m/z: calcd
for C8H11NO3: 169.07389 [M]+; found: 169.07336; HPLC (Chiralpak AD-
ACHTUNGTRENNUNGIndustries.
General procedure for the nitrocyclopropanation of bromonitromethane
to cyclic enones: (rac)-4-Methyl-mandelic acid (20 mol%) was added to
a stirred solution of catalyst (20 mol%) in PhCH3/CH2Cl2 (v/v, 7:3,
0.5 mL) and the solution was stirred for 5 min at room temperature.
After addition of enone (1.2 equiv), the mixture was stirred at the indi-
cated temperature for 10 min. The bromonitromethane (1 equiv) and
NMM (1 equiv) were added, separately, the tube was closed with a
rubber stopper, and stirring was continued for the indicated time. Then,
the crude reaction mixture was loaded onto a silica-gel column for purifi-
cation (EtOAc/hexane 1:5) to afford the nitrocyclopropanation product.
H, hexane/iPrOH 98:2, flow rate=0.5 mLminÀ1): t
AHCTUNGTREG(NNNU major)=46.6 min.
RACHTUNGTREN(NUNG minor)=43.9, tR-
General procedure for the nitrocyclopropanation of bromonitromethane
to aromatic (E)-a,b-unsaturated enones: CF3COOH (20 mol%) was
added to a stirred solution of catalyst (20 mol%) in CHCl3 (0.5 mL), and
the solution was stirred for 5 min at room temperature. After addition of
enone (2 equiv), the mixture was stirred for 10 min. The bromonitrome-
thane (1 equiv) was added, the tube was closed with a rubber stopper,
and stirring was continued for the indicated time. Then, the crude reac-
ACHTUNGTRENNUNG(1R,6S,7R)-7-NitrobicycloACHTUNTGREN[NUGN 4.1.0]heptan-2-one (4aa): The title compound
was obtained according to the general procedure. White solid; yield:
1
99%; [a]2D0 =À57.1 (c=0.5 in CH2Cl2); H NMR (300 MHz, CDCl3, 258C,
TMS): d=4.71 (t, 3J(H,H)=2.9 Hz, 1H), 2.81 (dd, 3J
ACHTUNGTRENNUNG ACHTUNTGREN(NUGN H,H)=2.5, 9.6 Hz,
tion mixture was loaded onto
a silica-gel column for purification
1H), 2.69–2.66 (m, 1H), 2.35 (td, 3J
ACTHNUTRGNE(NUG H,H)=4.53, 4.53, 17.94 Hz, 1H),
(EtOAc/hexane 1:10) to afford the Michael adduct as a white solid. The
resulting solid was dissolved in CH2Cl2 (0.15m). trans-Dimethylpiperazine
as a base was added, the tube was closed with a rubber stopper, and stir-
ring was continued for 24 h. The crude reaction mixture was loaded onto
a silica-gel column for purification (EtOAc/hexane 1:10) to afford the ni-
trocyclopropanation product.
2.22–2.13 (m, 2H), 2.06–1.99 (m, 1H), 1.91–1.83 (m, 1H), 1.63–1.52 ppm
(m, 1H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=201.2, 60.7, 37.3,
35.3, 26.9, 19.70, 18.3 ppm; MS (EI): m/z: 155 [M]+; HRMS-EI: m/z:
calcd for C7H9NO3: 155.05824 [M]+; found: 155.05768; HPLC (Chiralpak
AD-H, hexane/iPrOH 95:5, flow rate=0.6 mLminÀ1): t
RA(major)=38.5 min.
(1R,5S,6R)-6-NitrobicycloACTHNUTRGNE[NUG 3.1.0]hexan-2-one (4ba): The title compound
RACHTUNGTREN(NUNG minor)=35.5,
t CHTUNGTRENNUNG
General procedure for the one-pot nitrocyclopropanation of bromonitro-
methane to aromatic (E)-a,b-unsaturated enones: CF3COOH (20 mol%)
was added to a stirred solution of catalyst (20 mol%) in CHCl3 (0.5 mL),
and the solution was stirred for 5 min at room temperature. After addi-
tion of enone (2 equiv), the mixture was stirred for 10 min. The bromoni-
tromethane (1 equiv) was added, the tube was closed with a rubber stop-
per, and stirring was continued for 72 h. Then, trans-dimethylpiperazine
as a base was added and stirring was continued for 24 h. The crude reac-
R
was obtained according to the general procedure. White solid; yield:
95%; [a]2D0 =+11.8 (c=0.5 in CH2Cl2); 1H NMR (300 MHz, CDCl3,
258C, TMS): d=4.41 (t, 3J
ACTHUNRTGNE(GNU H,H)=1.5 Hz, 1H), 3.01–2.98 (m, 1H), 2.82
(d, 3J
ACHTUNGTRENNUNG(H,H)=6.6 Hz, 1H), 2.40–2.20 (m, 3H), 2.04–1.95 ppm (m, 1H);
13C NMR (75 MHz, CDCl3, 258C, TMS): d=208.3, 62.4, 37.5, 32.7, 31.0,
22.4 ppm; MS (EI): m/z: 141 [M]+; HRMS-EI: m/z: calcd for C6H7NO3:
141.04259 [M]+; found: 141.04217; HPLC (Chiralpak AD-H, hexane/
tion mixture was loaded onto
a silica-gel column for purification
(EtOAc/hexane 1:10) to afford the nitrocyclopropanation product.
iPrOH 95:5, flow rate=0.6 mLminÀ1):
tRACTHNGUTRE(NNUG minor)=39.2, tRACHTUNGRTEN(NUNG major)=
40.4 min.
1-(2-Nitro-3-phenylcyclopropyl)-1’-phenylmethanone (mixture of 9a and
10a): The title compound was obtained according to the general proce-
dure. White solid; yield: 70%; [a]2D0 =À3.0 (c=0.5 in CH2Cl2); 1H NMR
(400 MHz, CDCl3, 258C, TMS): major rotamer 9a peaks reported: d=
ACHTUNGTRENNUNG(1R,7S,8R)-8-NitrobicycloACHTUNTGREN[NUGN 5.1.0]octan-2-one (4ca): The title compound
was obtained according to the general procedure. White solid; yield:
85%; [a]2D0 =À20.1 (c=0.5 in CH2Cl2); H NMR (300 MHz, CDCl3, 258C,
1
8.13 (d, 3J
(H,H)=7.6 Hz, 2H), 7.36 (s, 5H), 5.10 (dd, 3J
4.40 (dd, 3J(H,H)=3.2, 7.5 Hz, 1H), 3.50 ppm (t, 3J
ACHTUNGTRENNUNG
(H,H)=8.2 Hz, 2H), 7.69 (t, 3J
ACHUTGTNRENNUG CAHTUNGTRENNUNG
TMS): d=4.65 (t, 3J
ACHTUNGTRENNUNG(H,H)=2.9 Hz, 1H), 2.70–2.80 (m, 2H), 2.37–2.44
A
ACHTUNGTRENNUNG
(m, 1H), 2.22–2.31 (m, 1H), 2.11–2.02 (m, 1H), 1.85–1.93 (m, 2H), 1.78
(s, 3H), 1.59–1.65 ppm (m, 1H); 13C NMR (75 MHz, CDCl3, 258C, TMS):
d=203.3, 62.9, 43.1, 39.9, 27.3, 26.9, 25.6, 24.4 ppm; MS (EI): m/z: 169
[M]+; HRMS-EI: m/z: calcd for C8H11NO3: 169.07389 [M]+; found:
169.07328; HPLC (Chiralpak AD-H, hexane/iPrOH 98:2, flow rate=
T
13C NMR (100 MHz, CDCl3, 258C, TMS): major rotamer 9a peaks re-
ported: d=193.6, 136.1, 134.3, 134.0, 130.9, 128.8, 128.5, 128.4, 66.5, 36.2,
30.8 ppm; d.r.: 9a/10a 94:6; MS (ESI): m/z: 268 [M+H]+; HRMS-EI: m/
z: calcd for C16H13NO3: 267.08954 (parent ion not found); found:
0.5 mLminÀ1): t
RACHTUNGTRENNUNG(minor)=21.1, tRACHTUNGTREN(NGUN major)=22.3 min.
Chem. Eur. J. 2009, 15, 972 – 979
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
977

Y. Wang et al.
235.11315 [MÀNO2]+; the ee of major diastereomer 9a was determined
to be >99% by chiral HPLC analysis (Chiralpak AD-H, hexanes/iPrOH
95:5, flow rate=1 mLminÀ1): tR(9a minor)=12.2, tR(9a major)=
14.9 min.
1H NMR (400 MHz, CDCl3, 258C, TMS): major rotamer 9 f peaks report-
ed: d=8.06 (d, 3J
7.55 (t, 3J
5.01 (dd, 3J
3.19 ppm (t, 3J
(H,H)=7.5 Hz, 2H), 7.67 (t, 3J
ACHUTGTNRENNUG CAHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
1-(2-(4-Chlorophenyl)-3-nitrocyclopropyl)-1’-phenylmethanone (mixture
of 9b and 10b): The title compound was obtained according to the gener-
al procedure. White solid; yield: 66%; [a]2D0 =À13.9 (c=0.5 in CH2Cl2);
1H NMR (400 MHz, CDCl3, 258C, TMS): major rotamer 9b peaks re-
TMS): major rotamer 9 f peaks reported: d=193.6, 143.7, 141.9, 136.1,
134.6, 129.3, 128.9, 116.2, 111.0, 66.4, 31.7, 28.1 ppm; d.r.: 9 f/10 f 92:8;
MS (ESI): m/z: 257 [M+H]+; HRMS-EI: m/z: calcd for C14H11NO4:
257.06881 (parent ion not found); found: 211.07582 [MÀNO2]+; the ee of
major diastereomer 9 f was determined to be 98% by chiral HPLC analy-
sis (Chiralpak AD-H, hexanes/iPrOH 95:5, flow rate=1 mLminÀ1): tR(9 f
minor)=17.9, tR(9 f major)=20.4 min.
3
3
ported: d=8.11 (d, J
G
U
3
3
7.58 (t, J
(H,H)=7.7 Hz, 2H), 7.34 (d, J
ACHTUNGTRENNUNG ACHTUNGTRENNUNG
(H,H)=8.6 Hz, 2H), 5.07 (dd, 3J
A
ACHTUNGTRENNUNG
(100 MHz, CDCl3, 258C, TMS): major rotamer 9b peaks reported: d=
193.3, 135.9, 134.6, 134.5, 130.2, 129.4, 129.2, 129.1, 128.5, 66.4, 35.3,
30.7 ppm; d.r.: 9b/10b 95:5; MS (ESI): m/z: 302 [M+H]+; HRMS-EI: m/
z: calcd for C16H12ClNO3: 301.05057 (parent ion not found); found:
255.05894 [MÀNO2]+; the ee of major diastereomer 9a was determined
to be 98% by chiral HPLC analysis (Chiralpak AD-H, hexanes/iPrOH
95:5, flow rate=1 mLminÀ1): tR(9b minor)=16.9, tR(9b major)=
18.7 min.
1-(2-Nitro-3-phenylcyclopropyl)-1’-(4-chlorophenyl)methanone (mixture
of 9g and 10g): The title compound was obtained according to the gener-
al procedure. White solid; yield: 77%; [a]2D0 =+8.5 (c=0.5 in CH2Cl2);
1H NMR (400 MHz, CDCl3, 258C, TMS): major rotamer 9g peaks report-
ed: d=8.06 (d, 3J
7.40–7.30 (m, 5H), 5.08 (dd, 3J
(H,H)=3.1, 7.3 Hz, 1H), 3.49 ppm (t, 3J
ACHTUNGTRENNUNG
A
ACHTUNGTREN(NUGN H,H)=8.3 Hz, 2H),
AHCTUNGTRENNUNG
E
(100 MHz, CDCl3, 258C, TMS): major rotamer 9g peaks reported: d=
192.8, 141.2, 134.5, 130.8, 130.1, 129.9, 128.9, 128.8, 128.5, 66.8, 36.7,
30.9 ppm; d.r.: 9g/10g 69:31; MS (ESI): m/z: 302 [M+H]+; HRMS-EI:
m/z: calcd for C16H12ClNO3: 301.05057 (parent ion not found); found:
255.05894 [MÀNO2]+; the ee of major diastereomer 9g was determined
to be 97% by chiral HPLC analysis (Chiralpak AD-H, hexanes/iPrOH
95:5, flow rate=1 mLminÀ1): tR(9g minor)=15.9, tR(9g major)=
24.7 min.
1-(2-(3-Chlorophenyl)-3-nitrocyclopropyl)-1’-phenylmethanone (mixture
of 9c and 9c): The title compound was obtained according to the general
procedure. White solid; yield: 75%; [a]2D0 =À23.1 (c=0.5 in CH2Cl2);
1H NMR (400 MHz, CDCl3, 258C, TMS): major rotamer 6c peaks report-
ed: d=8.11 (d, 3J
G
G
3
3
7.58 (t, J
N
8.8 Hz, 1H), 4.36 (dd, 3J
8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3, 258C, TMS): major rotamer 9c
peaks reported: d=193.5, 136.1, 134.9, 134.8, 133.0, 130.3, 129.4, 129.3,
129.1, 128.7, 127.2, 66.5, 35.5, 30.8 ppm; d.r.: 9c/10c 96: 4; MS (ESI): m/
z: 302 [M+H]+; HRMS-EI: m/z: calcd for C16H12ClNO3: 301.05057
(parent ion not found); found: 255.05894 [MÀNO2]+; the ee of major dia-
stereomer 9c was determined to be 99% by chiral HPLC analysis (Chir-
alpak AD-H, hexanes/iPrOH 95:5, flow rate=1 mLminÀ1): tR(9c
minor)=12.8, tR(9c major)=15.8 min.
1-(2-Nitro-3-phenylcyclopropyl)-1’-(4-trifluoromethylphenyl)methanone
(mixture of 9h and 10h): The title compound was obtained according to
the general procedure. White solid; yield: 80%; [a]2D0 =+8.1 (c=0.5 in
CH2Cl2); 1H NMR (400 MHz, CDCl3, 258C, TMS): major rotamer 9h
peaks reported: d=8.23 (d, 3J
8.1 Hz, 2H), 7.36 (s, 3H), 7.25 (d, 3J
(H,H)=3.3, 8.8 Hz, 1H), 4.38 (dd, 3J
(H,H)=3.3, 7.5 Hz, 1H), 3.52 ppm
(t, 3J(H,H)=8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): major rotamer
A
ACHTUNGTRENNUNG(H,H)=
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
9h peaks reported: d=193.3, 138.8, 135.5, 130.7, 130.6, 129.1, 129.0,
128.9, 126.4 ppm; d.r.: 9h/10h 60:40; MS (ESI): m/z: 336 [M+H]+;
HRMS-EI: m/z: calcd for C17H12F3NO3: 301.05057 (parent ion not
found); found: 255.05894 [MÀNO2]+; the ee of major diastereomer 6h
was determined to be >99% by chiral HPLC analysis (Chiralpak AD-H,
hexanes/iPrOH 95: 5, flow rate=1 mLminÀ1): tR(6d minor)=11.5, tR(6d
major)=17.7 min.
1-(2-Nitro-3-p-tolylcyclopropyl)-1’-phenylmethanone (mixture of 9d and
10d): The title compound was obtained according to the general proce-
1
dure. White solid; yield: 63%; [a]2D0 =À15.1 (c=0.5 in CH2Cl2); H NMR
(400 MHz, CDCl3, 258C, TMS): major rotamer 9d peaks reported: d=
8.12 (d, 3J(H,H)=7.6 Hz, 2H), 7.68 (t, 3J(H,H)=7.4 Hz, 1H), 7.57 (t, 3J-
ACHTUNGTRENNUNG ACHTUNGTRENNUGN
A
R
ACHTUNGTRNE(NUNG H,H)=
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
1-(2-Nitro-3-phenylcyclopropyl)-1’-(4-methoxyphenyl)methanone (mix-
ture of 9i and 10i): The title compound was obtained according to the
general procedure. White solid; yield: 80%; [a]2D0 =+2.3 (c=0.5 in
CH2Cl2); 1H NMR (400 MHz, CDCl3, 258C, TMS): major rotamer 9i
CDCl3, 258C, TMS): major rotamer 9d peaks reported: d=194.1, 138.6,
136.3, 134.5, 131.2, 129.7, 129.3, 128.8, 127.9, 66.9, 36.4, 31.0, 21.4 ppm;
d.r.: 9d/10d 90:10; MS (ESI): m/z: 282 [M+H]+; HRMS-EI: m/z: calcd
for C17H15NO3: 281.10519 (parent ion not found); found: 235.11315
[MÀNO2]+; the ee of major diastereomer 9d was determined to be 99%
by chiral HPLC analysis (Chiralpak AD-H, hexanes/iPrOH 95:5, flow
rate=1 mLminÀ1): tR(9d minor)=13.5, tR(9d major)=15.8 min.
peaks reported: d=8.11 (d, 3J
3J(H,H)=8.8 Hz, 2H), 5.07 (dd, 3J
(H,H)=3.4, 7.6 Hz, 1H), 3.92 (s, 3H), 3.48 ppm (t, 3J
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
1H); 13C NMR (100 MHz, CDCl3, 258C, TMS): major rotamer 9i peaks
reported: d=192.1, 164.7, 131.3, 132.0, 131.1, 129.3, 129.0, 128.7, 114.5,
66.6, 55.9, 36.3, 30.7 ppm; d.r.: 9i/10i 95:5; MS (ESI): m/z: 298 [M+H]+;
HRMS-EI: m/z: calcd for C17H15NO4: 297.10011 (parent ion not found);
found: 251.10696 [MÀNO2]+; the ee of major diastereomer 9i was deter-
mined to be 98% by chiral HPLC analysis (Chiralpak AD-H, hexanes/
iPrOH 95:5, flow rate=1 mLminÀ1): tR(9i minor)=27.9, tR(9i major)=
44.9 min.
1-(2-Nitro-3-(4-nitophenylcyclopropyl)-1’-phenylmethanone (mixture of
9e and 10e): The title compound was obtained according to the general
procedure. White solid; yield: 73%; [a]2D0 =À5.0 (c=0.5 in CH2Cl2);
1H NMR (400 MHz, CDCl3, 258C, TMS): major rotamer 9e peaks report-
ed: d=8.11 (d, 3J
(H,H)=7.6 Hz, 2H), 7.70 (t, 3J
G
3
3
7.58 (t, J
N
8.8 Hz, 1H), 4.36 (dd, 3J
N
8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3, 258C, TMS): major rotamer 9e
peaks reported: d=193.5, 136.1, 134.9, 134.8, 133.0, 130.3, 129.4, 129.3,
129.1, 128.7, 127.2, 66.5, 35.5, 30.8 ppm; d.r.: 9e/10e 99:1; MS (ESI): m/z:
313 [M+H]+; HRMS-EI: m/z: calcd for C16H12N2O5: 312.07462 (parent
ion not found); found: 266.08126 [MÀNO2]+; the ee of major diastereo-
mer 9e was determined to be 93% by chiral HPLC analysis (Chiralpak
OD-H, hexanes/iPrOH 90:10, flow rate=1 mLminÀ1): tR(9e minor)=
62.5, tR(9e major)=67.7 min.
1-(2-Nitro-3-phenylcyclopropyl)-1’-(4-chlorophenyl)methanone (mixture
of 9j and 10j): The title compound was obtained according to the general
procedure. White solid; yield: 76%; [a]2D0 =+1.4 (c=0.5 in CH2Cl2);
1H NMR (400 MHz, CDCl3, 258C, TMS): major rotamer 9j peaks report-
ed: d=8.68 (s, 1H), 8.12 (d, 3J
8.0 Hz, 1H), 7.99 (d, 3J(H,H)=8.7 Hz, 1H), 7.93 (d, 3J
1H), 7.65 (m, 2H), 7.39 (s, 5H), 5.15 (dd, J
(dd, 3J(H,H)=3.1, 7.4 Hz, 1H), 3.57 ppm (t, 3J
A
ACHTUNGTRENNUNG(H,H)=
A
ACHTUNGTRENNUNG
3
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
1-(2-(Furan-3-yl)3-nitrocyclopropyl)-1’-phenylmethanone (mixture of 9 f
and 10 f): The title compound was obtained according to the general pro-
cedure. White solid; yield: 60%; [a]2D0 =+28.3 (c=0.5 in CH2Cl2);
13C NMR (100 MHz, CDCl3): major rotamer 9j peaks reported: 193.8,
136.3, 133.6, 132.7, 131.2, 131.0, 129.5, 129.3, 129.1, 128.9, 128.2, 127.5,
123.8, 66.9, 36.5, 31.1 ppm; d.r.: 9j/10j 87:13; MS (ESI): m/z: 318
978
www.chemeurj.org
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 972 – 979

Synthesis of Functionalized Nitrocyclopropanes
FULL PAPER
[M+H]+; HRMS-EI: m/z: calcd for C20H15NO3: 317.10519 (parent ion
not found); found: 271.11280 [MÀNO2]+; the ee of major diastereomer
9j was determined to be 96% by chiral HPLC analysis (Chiralpak AD-
H, hexanes/iPrOH 95:5, flow rate=1 mLminÀ1): tR(9j minor)=18.9,
tR(9j major)=20.7 min.
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Acknowledgements
The work was financially supported by the National Natural Science
Foundation of China (grant no. 20672061, China) and 863 Project (no.
2007AA05Z102, China). We also thank the Nankai University State Key
Laboratory of Elemento-Organic Chemistry for support.
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Received: August 10, 2008
Published online: December 10, 2008
Chem. Eur. J. 2009, 15, 972 – 979
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