Asymmetric Michael addition of acetone to β-nitrostyrenes catalyzed by novel organocatalysts derived from D-isomannide or Lisoidide

Article abstract of DOI:10.3998/ark.5550190.p008.429

Novel bifunctional organocatalysts were prepared from D-isomannide or L-isoidide in three steps. These catalysts were then evaluated in the asymmetric Michael addition of acetone to trans-.-nitrostyrenes. Although moderate enantioselectivities were observed, this study has highlighted that a simple chiral primary diamine can catalyze this reaction. Furthermore, the reaction was also performed with an isomannide-derived diimine which was transformed in situ into the active catalyst under acidic conditions leading to the best enantioselectivity. ARKAT-USA, Inc.

Full text of DOI:10.3998/ark.5550190.p008.429

See discussions, stats, and author profiles for this publication at: http://www.researchgate.net/publication/263121702
Asymmetric Michael addition of acetone tobeta-
nitrostyrenes catalyzed by novel organocatalysts
derived from D-isomannide or Lisoidide
ARTICLE in ARKIVOC: ARCHIVE FOR ORGANIC CHEMISTRY · JANUARY 2014
DOI: 10.3998/ark.5550190.p008.429
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General Papers
ARKIVOC 2014 (iv) 215-227
Asymmetric Michael addition of acetone to -nitrostyrenes
catalyzed by novel organocatalysts derived from D-isomannide or L-
isoidide
Ling-Yan Chen,a,b Stéphane Guillarme,a Andrew Whiting,c and Christine Saluzzoa,*
a IMMM, UMR CNRS 6283, Faculté des Sciences, Université du Maine, Av. O. Messiaen,
72085 Le Mans Cedex 09, France
b College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science,
201620, China
c Department of Chemistry, Durham University, Science Laboratories, South Road,
Durham, DH1 3LE, UK
E-mail: Christine.Saluzzo@univ-lemans.fr
DOI: http://dx.doi.org/10.3998/ark.5550190.p008.429
Abstract
Novel bifunctional organocatalysts were prepared from D-isomannide or L-isoidide in three
steps. These catalysts were then evaluated in the asymmetric Michael addition of acetone to
trans--nitrostyrenes. Although moderate enantioselectivities were observed, this study has
highlighted that a simple chiral primary diamine can catalyze this reaction. Furthermore, the
reaction was also performed with an isomannide-derived diimine which was transformed in situ
into the active catalyst under acidic conditions leading to the best enantioselectivity.
Keywords: Organocatalysis, isomannide, isoidide, Michael addition, monothiourea, nitroalkenes
Introduction
Asymmetric organocatalysis has been revived as an important field of asymmetric synthesis
since the independent work of List,1 MacMillan,2 and Barbas.3 Inspired by natural enzymatic
systems, successful efforts have been directed towards the development of bifunctional
organocatalysts containing a Lewis-basic amine and a hydrogen bond donor able to activate both
nucleophile and electrophile simultaneously.4-6 In particular, bifunctional amine-thiourea-based
catalysts have proved to be efficient in various asymmetric transformations owing to the ability
of the thiourea moiety to highly activate carbonyl or nitro groups through double hydrogen-
bonding interactions.7,8 Therefore, this kind of organocatalyst has been widely studied in
asymmetric nitro-Michael addition reactions.9,10 The first asymmetric Michael addition of
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ketones to trans--nitrostyrenes was performed independently by List11 and Barbas3 involving
proline as catalyst. Since these reports, successful examples using bifunctional tertiary or
secondary amine-thiourea catalysts have been reported.12-22
Since Tsogoeva23 and Jacobsen24 demonstrated that a primary amine-thiourea catalyst can act
as efficient bifunctional catalyst for the asymmetric nitro Michael addition, such bifunctional
organocatalysts have attracted much attention owing to their easy preparation from chiral
diamines.25-32 However, the chiral scaffold of these reported organocatalysts is limited and is
mostly derived from 1,2-diaminocyclohexane and 1,2-phenylethylenediamine.
As part of an ongoing program, we were interested in the design of new bifunctional
organocatalysts from original chiral building blocks, i.e. from D-isomannide and L-isoidide; two
side-products of the starch industry. Although numerous examples of polymers containing this
backbone have been reported,33 only a few examples in the field of asymmetric catalysis have
been investigated. In asymmetric organometallic catalysis, ligands derived from
dianhydrohexitols have already been used to perform Diels-Alder reactions,34 nucleophilic
addition to aldehydes,35 asymmetric allylic substitution,36,37 hydrogen transfer reduction of
prochiral ketones38-40 and asymmetric hydrogenation of olefins.41,42 Recently, we described the
first example of organocatalysts derived from dianhydrohexitols for the asymmetric Friedel-Craft
alkylation of indoles.43 Herein, we report our preliminary results on asymmetric Michael addition
of acetone to trans--nitrostyrenes catalyzed by chiral thioureas and imines organocatalysts
derived from D-isomannide- or L-isoidide.
Results and Discussion
Herein, we report our preliminary results on asymmetric Michael addition of acetone to trans--
nitrostyrenes catalyzed by D-isomannide- or L-isoidide-derived organocatalysts 1-8 (Figure 1).
R
CF3
H2N
H2N
N
O
O
O
S
1, R =
2, R =
N
H
CF3
O
O
O
NHR
NHR
N
CF3
R
5, R = H
S
S
7, R =
8, R =
N
N
H
6, R =
N
H
CF3
S
3, R =
N
N
H
4, R = H
Figure 1. D-Isomannide and L-isoidide-derived organocatalysts.
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Catalysts 1-3 were obtained after reaction of one equivalent of the corresponding
isothiocyanate and diamine 4, which was obtained in three steps from D-isomannide (Scheme 1).
Around 10-15% of the corresponding dithioureas were also isolated. Monothiourea 6 was
prepared from diamine 5 which was isolated in three steps from L-isoidide.43 Finally, using the
same conditions as preparing thioureas 1-3, catalyst 6 was successfully obtained in 40% yield
(Scheme 1).
CF3
ArNCS
(1 equiv)
THF, rt
1, 51%, Ar =
H2N
H2N
O
HO
O
O
3 steps
CF3
S
Ref.16
2, 57%, Ar =
3, 48%, Ar =
O
O
HN
O
NH2
OH
Ar
HN
D-Isomannide
4
ArNCS
(1 equiv)
THF, rt
H2N
O
H2N
HO
O
O
CF3
CF3
3 steps
S
Ref.16
O
6, 40%, Ar =
HN
O
O
NH2
OH
Ar
HN
5
L-isoidide
Scheme 1. Synthesis of monothioureas 1-3 and 6.
Diimines 7 and 8 were also prepared as precursor of amine-imine organocatalysts according to
Cheng et al.44 They were prepared from the corresponding diamine 4 under the usual conditions
(Scheme 2).
Scheme 2. Synthesis of diimine derivatives.
With these organocatalysts in hand, the Michael addition of acetone to trans--nitrostyrene 9a,
using 20 mol% of catalyst 1, was evaluated without any solvent (Table 1). In these conditions,
the desired product was obtained with moderate yield and poor enantioselectivity (Table 1, entry
1). To improve the reaction rate and the enantioselectivity, we investigated the effect of acidic
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additives (1 equivalent related to the catalyst) on the reaction (Table 1, entries 1-9). Compared to
the reaction performed without additive, in the presence of benzoic acid, the chemical yield and
enantioselectivity were improved (Table 1, entries 1 and 2). With mandelic acids, both yields and
ees decreased (Table 1, entries 3 and 4), no matched-mismatched double diastereoselectivity
effects were observed. Moreover, the chirality of the acid had no influence on the
enantioselectivity; the same major isomer being formed (entries 3 and 4). In the case of 2,2,2-
trichloroacetic acid (TCA), although better enantioselectivity was obtained, the product was
isolated along with a side-product even after purification (Table 1, entry 5). The use of a strong
acid such as trifluoroacetic acid led to deactivation of the catalyst (Table 1, entry 6). p-
Toluenesulfonic acid was also not suitable for this asymmetric reaction (Table 1, entry 7).
Finally, a weaker acid, such as acetic acid, gave the best results in terms of yield and ee (Table 1,
entry 9). However, the use of larger amounts or less than 20 mol% of acetic acid had a dramatic
effect on both yields and ees (Table 1, entries 10-12).
Table 1. Catalytic asymmetric Michael addition of acetone with trans--nitrostyrene 9a with
different additivesa
O
O
NO2
1
Cat.
NO2
9a
+
Ph
additive
neat, rt, 2 d
Ph
10a
Entry
1
Additive (mol%)
Yield (%)b
EE (%)c (R)d
-
44
77
24
39
95e
-
<5
15
10
8
27
-
2
3
4
5
PhCO2H (20)
D-Mandelic acid (20)
L-Mandelic acid (20)
TCA (20)
6
TFA (20)
7
8
9
10
11
12
p-TsOH (20)
PhOH (20)
AcOH (20)
AcOH (75)
AcOH (175)
AcOH (10)
29
39
87
87
24
68
11
24
23
7
10
6
a Reaction conditions: 9a (0.1 mmol), acetone (0.4 mL), 1 (20 mol%), additive at rt for 2 d.
b Yield of product isolated after flash chromatography.
c Determined by HPLC analysis (Phenomenex Lux 5 cellulose-2, i-octane/i-PrOH = 9/1).
d
Absolute configuration was determined by comparison of the optical rotation with the known
compounds in the literature.45
e % Conversion.
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Using the optimized conditions from Table 1 (entry 9), we then explored the different
organocatalysts. Among all the primary amine-thiourea-based catalysts 1-3 and 6, catalyst 1 had
the best performance, affording yields up to 87%. However, the ees were all in the same range
(around 25%, Table 2, entries 1-3), except for catalyst 6 which led to a racemic product (Table 2,
entry 6).
The formation of the racemic compound can be explained by the proximity of the two nitrogen
group in the ‘endo’-position which perhaps give rise to a strong intramolecular hydrogen bond
either between the thiourea moiety and the oxygen of the bicycle or between the primary amine
and the thiourea groups.46
The same stereochemical outcome was observed with the chiral primary diamine 5 (Table 2,
entry 5). Surprisingly, the simple diamine catalyst 4 gave promising results in terms of both yield
and ee (Table 2, entry 4). Although some examples using secondary or secondary-tertiary
diamines as catalysts for this reaction have been reported,47,48 to the best of our knowledge, a
successful example with a chiral primary diamine has not yet been described. Finally, the
asymmetric reaction was also performed in solvents such as toluene, CHCl3, DCM and MTBE,
but the reaction rate dramatically decreased in all cases.
Table 2. Catalytic asymmetric Michael addition of acetone with trans--nitrostyrene 9a with
different catalystsa
Catalyst
AcOH
O
O
NO2
NO2
+
Ph
neat, rt
Ph
9a
10a
Entry Catalyst Time (h)
Yieldb (%)
EEc (%)
23
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
48
48
48
48
48
48
48
48
87
43
34
65
36
58
34
39
26
28
40
<5
<5
37
59
a
Reaction conditions: 9a (0.1 mmol), acetone (0.4 mL), catalyst 1-9 (20 mol%), AcOH (20
mol%.
b Yield of product isolated after flash chromatography.
c Determined by HPLC analysis (Phenomenex Lux 5 cellulose-2, i-octane/i-PrOH = 9/1).
With the diimine catalysts 7 and 8, some catalytic effect was observed. We think that, in the
presence of acetic acid, the diimines are likely to be transformed in situ into primary amine-
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imines which might be potential catalysts, as demonstrated by Cheng et al.44 With the quinoline-
derived diimine catalyst 8, we assumed that the pre-catalyst 8 led to the catalyst 11, able to both
activate the nucleophile and electrophile. The activation of the nitro group is possible by a
hydrogen-bonding interaction after in situ formation of the quinolinium cation (intermediate A,
Scheme 3). In that case, the ee reached 59% (Table 2, entry 9). The difference in the ee observed
between that obtained from pre-catalyst diimines 7 and 8 is probably attributed to the presence of
the second aromatic ring in compound 8 which likely induced additional steric hindrance (Table
2, entries 7 and 8). Our attempts to perform the synthesis of the pure amino-imine 11 to test its
reactivity on the catalytic reaction were unsuccessful as the organocatalyst could not be obtained
pure even after chromatography on deactivated silica gel.
The asymmetric Michael addition was then performed with other substrates 9b-e to expand
upon the scope of this reaction (Table 3). The reaction was carried out with catalyst 4 which
afforded the best results in terms of both yields and enantioselectivities under the optimal
conditions.
Scheme 3. Possible transition state A.
The reaction between different nitrostyrenes which had either electron-withdrawing groups or
electron-donating groups were studied. The corresponding adducts were isolated in moderate to
good yields and with ees in the similar range to those obtained previously (ca. 40% ee) (Table 3,
entries 1-4). However, when the naphthyl nitroolefin 9e was used, the ee of product 10e was only
24% (Table 3, entry 5). Furthermore, with our catalytic system, the Michael addition of aromatic
ketones, such as acetophenone, was unsuccessful contrary to the Xu’s catalysts.31
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Table 3. The scope of catalytic asymmetric Michael addition of ketones with
trans--nitrostyrenes 9a-ea
R1
4
Cat.
AcOH
O
O
neat, rt, 2 d
NO2
+
R2
NO2
R2
R1
9a-e
10a-e
Entry
R1
Me
Me
Me
Me
Me
Ph
R2
Product
10a
10b
10c
10d
10e
-
Yieldb (%)
EEc (%)
1
2
3
4
5
6
Ph
4-ClC6H4
4-Tol
4-MeOC6H4
Naphth-1-yl
Ph
65
62
63
51
72
-
40
37
39
40
24
-
a Reaction conditions: 9a-e (0.1 mmol), acetone (0.4 mL), 4 (20 mol%), AcOH (20 mol%).
b Yield of product isolated after flash chromatography.
c Determined by HPLC analysis (Phenomenex Lux 5 cellulose-2, i-octane/i-PrOH = 9/1).
Conclusions
In conclusion, we have developed a new series of organocatalysts derived from D-isomannide
and L-isoidide, which have shown their ability to catalyze for the first time the asymmetric
Michael addition of acetone to trans--nitroolefins. Although moderate enantioselectivities and
yields were observed, this study has shown that the reaction can be catalyzed by a simple chiral
primary diamine. On the other hand, the use of a chiral diimine in acidic conditions led to the
best enantioselectivity, however, the reaction rate was low. Owing to their ease of preparation
from D-isomannide even on large scale, these catalysts are ideal candidates for wider studies in
this area. To determine the stereochemical outcome using the diimine catalyst and to improve the
reaction rate, further investigations are in progress in our laboratory and the results will be
reported in due course.
Experimental Section
General. Unless otherwise noted, solvents and starting materials were obtained from commercial
1
suppliers. All chemicals used were of reagent grade without further purification before use. H
and 13C NMR spectra were recorded on a Bruker Avance (200 or 400 MHz for 1H, and 50 or 100
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13
MHz for C) in CDCl3, MeOH-d4, DMSO-d6 or acetone-d6. Chemical shifts were recorded in
1
13
ppm (δ) relative to CHCl3 on 7.26 or TMS on 0.00 for H NMR and 77.0 for C NMR, to
MeOH on 3.31 for 1H NMR and 49.0 for 13C NMR, to DMSO on 2.50 for 1H NMR and 39.5 for
13C NMR, to acetone on 2.05 for H NMR and 29.8 for 13C NMR. Melting points were
1
determined on a Reichert Thermoval apparatus and are uncorrected. Optical rotations values
were recorded using a Perkin-Elmer 343 polarimeter. FT-IR spectra were performed on a Nicolet
AVATAR 370 DTGS Thermo Electron Corporation apparatus and band positions are given in
cm-1. High resolution mass spectra were recorded on a Waters Micromass GCT PremierTM.
Diamines 4 and 5 were prepared according to the procedure described in the literature.43
General procedure for the synthesis of catalysts 1-3 and 6. To a stirred solution of diamine 4
(0.5 mmol) in THF (8 mL) was slowly added isothiocyanate (0.5 mmol) in THF (2.5 mL). After
stirring at rt for 2 h, the reaction mixture was concentrated, and the residue was purified by
column chromatography (eluent: DCM/MeOH: 10/1 to 5/1) to afford monothioureas 1-3 and 6.
Monothiourea 1. Prepared according to the general procedure to provide the product 1 as a solid
in 51% yield, mp: 94-95 oC; []D20 = + 36.5 (c 0.96, DCM); 1H NMR (400 MHz, CDCl3) 8.94
(br s, 1H), 7.90 (s, 2H), 7.62 (s, 1H), 7.34 (br s, 1H), 4.81 (d, J 4.3 Hz, 1H), 4.73 (br s, 1H), 4.44
(d, J 4.3 Hz, 1H), 4.05-4.01 (m, 1H), 3.92 (dd, J 9.7, 4.1 Hz, 1H), 3.81 (d, J 9.7 Hz, 1H), 3.74-
3.68 (m, 1H), 3.58-3.56 (m, 1H), 2.68 (br s, 2H).
Monothiourea 2. Prepared according to the general procedure to provide the product 2 as a solid
o
20
in 57% yield, mp: 78.8-80.5 C; []D = + 47.4 (c 1.16, DCM). IR (ATR, cm-1): 3250, 2933,
2872, 1593, 1526, 1495, 1449, 1313, 1242, 1061, 900, 842, 758, 693, 470; 1H NMR (200 MHz,
CDCl3) 8.48 (s, 1H), 7.47-7.38 (m, 2H), 7.33-7.21 (m, 3H), 6.24 (dm, J 5.8 Hz, 1H), 4.86 (br s,
1H), 4.75 (d, J 4.2 Hz, 1H), 4.29 (d, J 4.2 Hz, 1H), 3.97 (dd, J 10.0, 4.6 Hz, 1H), 3.91 (dd, J 9.4,
4.6 Hz, 1H), 3.75 (dd, J 10.0, 2.0 Hz, 1H), 3.67 (dd, J 9.4, 2.2 Hz, 1H), 3.52-3.48 (m, 1H), 1.66
13
(s, 2H). C NMR (50 MHz, CDCl3) 180.5, 136.2, 130.1, 127.2, 124.9, 89.1, 86.0, 75.1, 71.8,
61.5, 58.0. HRMS m/z calcd for C13H18N3O2S [M+H]+ = 280.1118, found 280.1120.
Monothiourea 3. Prepared according to the general procedure to provide the product 3 as a solid
o
20
in 48% yield, mp: 160.7-161.5 C, []D = + 5.23 (c 1.51, THF), IR (film, cm-1): 3358, 3056,
2947, 2880, 1712, 1541, 1398, 1272, 1056, 919, 777; 1H NMR (400 MHz, MeOH-d4) 7.94-7.91
(m, 2H), 7.87-7.85 (m, 1H), 7.57-7.47 (m, 4H), 4.89 (s, 2H), 4.70 (d, J 3.3 Hz, 1H), 4.30 (d, J 3.8
Hz, 1H), 3.98 (dd, J 9.8, 5.3 Hz, 1H), 3.93 (dd, J 9.8, 4.8 Hz, 1H), 3.69-3.65 (m, 2H). 13C NMR
(100 MHz, MeOH-d4) δ 183.8, 136.1, 135.0, 131.5, 129.5, 129.0, 127.8, 127.5, 126.8, 126.4,
123.7, 88.9, 87.8, 74.3, 72.8, 62.8, 58.6. HRMS m/z calcd for C17H20N3O2S [M+H]+ = 330.1276,
found 330.1261.
Monothiourea 6. Prepared from diamine 5 according to the general procedure to provide the
product 6 as a yellow solid in 40% yield, mp: 115.6-117.5 oC, []D20 = + 3.1 (c 1.5, CHCl3), 1H
NMR (400 MHz, MeOH-d4) 8.26 (s, 2H), 7.63 (s, 1H), 5.06-5.00 (m, 1H), 4.72 (dd, J 5.1, 4.2
Hz, 1H), 4.55 (dd, J 4.6, 4.2 Hz, 1H), 4.35 (dd, J 8.2, 7.9 Hz, 1H), 4.12 (dd, J 8.2, 7.5 Hz, 1H),
3.65 (ddd, J 9.5, 7.5, 4.6 Hz, 1H), 3.55 (dd, J 8.8, 8.6 Hz, 1H), 3.49 (dd, J 9.5, 8.6 Hz, 1H). 13C
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NMR (100.6 MHz, MeOH-d4) 182.9, 143.2, 132.7 (q, J 33.2 Hz), 124.8 (q, J 271.6 Hz), 123.2,
117.8, 83.9, 83.4, 73.6, 72.6, 59.4, 56.6. HRMS m/z calcd for C15H16F6N3O2S [M+H]+ =
416.0867, found 416.0858.
General procedure for the synthesis of catalysts 7-8
To a solution of diamine 4 (200 mg, 1.39 mmol) in dry DCM (8 mL) was added anhydrous
MgSO4 (332.4 mg) and the aldehyde (2.77 mmol). The resulting mixture was stirred for 16 h at
rt. The MgSO4 was filtered off. After evaporation of the solvent, the product was recrystallized
in Et2O.
Diimine 7. Prepared according to the general procedure to provide the product 7 as a solid in
o
20
85% yield, mp: 122.3-123.3 C; []D = + 6.9 (c 0.82, CHCl3). IR (ATR, cm-1): 2880, 2851,
1
1644, 1585, 1565, 1468, 1436, 1282, 1087, 1067, 1049, 991, 955, 905, 819, 772, 614. H NMR
(400 MHz, CDCl3) 8.66 (d, J 4.9 Hz, 2H), 8.47 (s, 2H), 8.02 (d, J 7.9 Hz, 2H), 7.74 (td, J 7.7, 1.6
Hz, 2H), 7.33 (dd, J 7.6, 4.8 Hz, 2H), 4.80 (s, 2H), 4.24-4.20 (m, 2H), 3.95 (dd, J 11.1, 4.7 Hz,
2H). 13C NMR (100 MHz, CDCl3) δ 162.9, 154.1, 149.5, 136.5, 125.0, 121.5, 89.0, 75.8, 74.0.
Diimine 8. Prepared according to the general procedure to provide the product 8 as a solid in
o
20
88% yield, mp: 145.1-146.5 C; []D = + 11.6 (c 1.0, CHCl3). IR (ATR, cm-1): 3052, 2901,
1
2872, 1638, 1589, 1556, 1495, 1454, 1422, 1205, 1099, 1066, 1046, 972, 886, 825, 739. H
NMR (200 MHz, CDCl3) 8.65 (s, 2H), 8.16-8.12 (m, 6H), 7.87-7.71 (m, 4H), 7.63-7.54 (m, 2H),
4.87 (s, 2H), 4.34-4.29 (m, 2H), 4.29-4.23 (m, 2H), 4.03 (d, J 1.8 Hz, 1H), 3.99 (d, J 1.8 Hz,
1H). 13C NMR (100 MHz, CDCl3) 163.4, 154.4, 147.8, 136.5, 129.9, 129.7, 128.9, 127.7, 127.6,
118.5, 89.0, 75.9, 74.2. HRMS m/z calcd for C26H23N4O2 [M+H]+ = 423.1821, found 423.1817.
General procedure for Michael addition of ketones to nitrostyrenes
To a solution of catalyst (0.02 mmol) and AcOH (0.02 mmol) in 0.4 mL of ketone in a Schlenk
tube was added after 30 min nitrostyrene (0.1 mmol). The reaction was kept stirring for 2 d. The
mixture was introduced into a flash column chromatography with c-hexane/EtOAc (4/1, v/v) as
eluent to afford the product.
o
5-Nitro-4-phenylpentan-2-one (10a).17,24 Colorless solid, mp: 94.4-95.4 C (lit.,17 mp: 90-92
oC), 65% yield, []D20 - 0.95 (c 0.75, CHCl3) 40% ee (Pure R enantiomer lit. []D20 – 2.1 [c 0.80,
CHCl3)45], [Phenomenex Lux 5 cellulose-2, isooctane/i-PrOH = 90/10, Flow rate = 0.90
1
mL/min, UV = 220 nm, tR = 28.35 min (major) and 30.40 min], H NMR (200 MHz, CDCl3)
7.34-7.20 (m, 5H), 4.69 (dd, J 12.3, 6.8 Hz, 1H), 4.60 (dd, J 12.3, 7.7 Hz, 1H), 4.02-3.99 (m,
13
1H), 2.91 (d, J 7.4 Hz, 2H), 2.11 (s, 3H). C NMR (100 MHz, CDCl3) 205.3, 138.8, 129.0,
127.9, 127.3, 79.4, 46.1, 39.0, 30.3.
o
4-(4-Chlorophenyl)-5-nitropentan-2-one (10b). Colorless solid, mp: 77.1-78.2 C (lit.,49 mp:
o
89-91 C), 62% yield, 37% ee [Phenomenex Lux 5 cellulose-2, isooctane/i-PrOH = 90/10,
1
Flow rate = 1.0 mL/min, UV = 210 nm, tR = 43.92 min (major) and 50.10 min], H NMR (200
MHz, CDCl3) 7.33-7.27 (m, 2H), 7.19-7.14 (m, 2H), 4.69 (dd, J 12.5, 6.8 Hz, 1H), 4.57 (dd, J1 =
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12.5, 7.8 Hz, 1H), 4.06-3.92 (m, 1H), 2.89 (d, J 6.9 Hz, 2H), 2.13 (s, 3H). 13C NMR (100 MHz,
CDCl3) 204.9, 137.3, 133.7, 129.2, 128.8, 79.1, 45.9, 38.4, 30.3.
o
o
5-Nitro-4-p-tolylpentan-2-one (10c). Colorless solid, mp: 61.0-62.8 C (lit.,49 mp: 70-72 C),
63% yield, 39% ee [Phenomenex Lux 5 cellulose-2, isooctane/i-PrOH = 90/10, Flow rate =
0.90 mL/min, UV = 210 nm, tR = 25.43 min (major) and 28.58 min], H NMR (200 MHz,
1
CDCl3) 7.16-7.07 (m, 4H), 4.68 (dd, J 12.4, 7.2 Hz, 1H), 4.57 (dd, J 12.4, 7.2 Hz, 1H), 4.04-3.90
13
(m, 1H), 2.90 (d, J 7.1 Hz, 2H), 2.31 (s, 3H), 2.11 (s, 3H). C NMR (100 MHz, CDCl3) 205.5,
137.6, 135.7, 129.7, 127.2, 79.6, 46.2, 38.7, 30.4, 21.0.
4-(4-Methoxy-phenyl)-5-nitro-pentan-2-one (10d). Colorless solid, 51% yield, 40% ee
[Phenomenex Lux 5 cellulose-2, isooctane/i-PrOH = 90/10, Flow rate = 0.90 mL/min, UV =
210 nm, tR = 43.92 min (major) and 50.10 min], 1H NMR (200 MHz, CDCl3) 7.17-7.10 (m, 2H),
6.89-6.82 (m, 2H), 4.67 (dd, J 12.3, 6.9 Hz, 1H), 4.55 (dd, J 12.3, 7.5 Hz, 1H), 4.03-3.89 (m,
13
1H), 3.78 (s, 3H), 2.89 (d, J 7.2 Hz, 2H), 2.12 (s, 3H). C NMR (100 MHz, CDCl3) 205.5,
159.1, 130.6, 128.4, 114.4, 79.7, 55.2, 46.3, 38.4, 30.4.
4-(Naphthalen-1-yl)-5-nitropentan-2-one (10e). 72% yield, 24% ee [Phenomenex Lux 5
cellulose-2, isooctane/i-PrOH = 90/10, Flow rate = 1.0 mL/min, UV = 210 nm, tR = 27.35 min
(major) and 36.53 min], 1H NMR (200 MHz, CDCl3) 8.17 (d, J 8.6 Hz, 1H), 7.91-7.86 (m, 1H),
7.79 (d, J 8.0 Hz, 1H), 7.62-7.30 (m, 4H), 5.02-4.87 (m, 1H), 4.80 (s, 1H), 4.77 (d, J 1.6 Hz,
13
1H), 3.21-2.99 (m, 2H), 2.14 (s, 3H). C NMR (100 MHz, CDCl3) 205.5, 134.7, 134.1, 130.8,
129.2, 128.5, 126.9, 126.1, 125.2, 123.6, 122.2, 78.8, 46.0, 33.4, 30.2.
Acknowledgements
The authors thank the Région «Pays de la Loire» for a post-doctoral fellowship (L.-Y. C.), the
CNRS and the Ministère de l’Enseignement Supérieur et de la Recherche. Acknowledgments are
also made to F. Legros, P. Gangnery and A. Durand for their technical assistants.
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