Enantio- and diastereoselective Michael additions of C-succinimidyl esters to nitro olefins using cinchonine-derived bifunctional organocatalysts

Article abstract of DOI:10.1016/j.tetasy.2011.06.002

A novel bifunctional organocatalytic Michael addition of a succinimide-derived pronucleophile to nitro olefins is described. The use of a range of nitro olefins afforded Michael adducts containing contiguous quaternary and tertiary stereogenic centres in

Full text of DOI:10.1016/j.tetasy.2011.06.002

Tetrahedron: Asymmetry 22 (2011) 1147–1155
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantio- and diastereoselective Michael additions of C-succinimidyl esters
to nitro olefins using cinchonine-derived bifunctional organocatalysts
Pavol Jakubec a, Dane M. Cockfield b, Peter S. Hynes b, Ed Cleator c, Darren J. Dixon a,
⇑
a The Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK
b School of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, UK
c Merck Sharp Dohme Research Laboratories, Global Process Research, Hoddesdon, Hertfordshire EN11 9BU, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel bifunctional organocatalytic Michael addition of a succinimide-derived pronucleophile to nitro
olefins is described. The use of a range of nitro olefins afforded Michael adducts containing contiguous qua-
ternary and tertiary stereogenic centres in high enantioselectivities and moderate diastereoselectivities.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 12 May 2011
Accepted 1 June 2011
Available online 23 July 2011
1. Introduction
although outstanding in many reactions, is not necessarily the
optimal catalyst for all reagent combinations.3,4
Bifunctional Brønsted base, hydrogen-bond donor organocata-
lysts based on the 9-amino(9-deoxy) epicinchona scaffold, intro-
duced by our group and others, have recently emerged as highly
selective catalysts for numerous addition reactions of carbon-
and heteroatom-centred pronucleophiles to reactive electrophiles,
such as electron deficient C–C multiple bonds, carbonyl com-
pounds and imines.1,2 In our original work describing the highly
enantioselective Michael addition of malonate pronucleophiles to
nitro olefins, a library of bifunctional organocatalysts derived from
9-amino(9-deoxy) epicinchonine was synthesized and screening of
this library allowed the identification of thiourea catalyst 1a
(Fig. 1) as the optimum catalyst for this reagent combination. Sub-
sequent reports by our group and others have revealed that 1a,
In continuation of our work in the field of bifunctional organo-
catalysed Michael additions to nitro olefins, we were interested in
identifying other synthetically relevant pronucleophiles, specifi-
cally prochiral pronucleophiles, which would afford adducts with
two adjacent stereogenic centres. Accordingly, issues of both rela-
tive and absolute stereocontrol in the screening of our catalyst li-
brary would arise.
Although the commercially available cyclic b-ketoesters have
been extensively studied in the stereoselective Michael addition
to nitro olefins,5 to date C-succinimidyl esters have not been re-
ported as pronucleophiles despite their high functional group den-
sity and potential synthetic utility. The use of such pronucleophiles
would indeed give rise to adducts containing contiguous
N
H
N
H
N
H
N
H
N
H
HN
S
HN
HN
HN
S
HN
O
O
N
N
N
O
O
N
N
HN
S
R
S
HN
S
F3C
CF3
1a
1b
1c R = 9-EACN
Figure 1. Cinchona derived organocatalysts.
1d
1e
⇑
Corresponding author.
E-mail address: Darren.dixon@chem.ox.ac.uk (D.J. Dixon).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.06.002

1148
P. Jakubec et al. / Tetrahedron: Asymmetry 22 (2011) 1147–1155
RNCS(O)
RT, THF
N
H
N
H
HN
HN
N
N
HN
R
S
2
1
N
H
N
H
N
H
HN
HN
HN
HN
N
N
N
S
HN
S
HN
O
O
F3C
CF3
H
1h, 91%
1g, 92%
1f
N
H
N
H
N
HN
HN
HN
HN
N
N
N
HN
S
S
HN
S
1j, 75%
Scheme 1. Synthesis of cinchonine derived organocatalysts.
1i, 90%
1k, 82%
O
NO2
quaternary and tertiary stereogenic centres and, accordingly, is-
sues of both relative and absolute stereocontrol would arise in
the screening of our catalyst library. Herein we report our findings.
Table 1
Catalyst screen for the Michael addition of C-succinidyl ester 4 to nitrostyrene 3a
a,b
Entry
Catalyst
Conv
(%)
drb
eec (%)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
>95
>95
43
71
69
>95
86
95
>95
94
>95
3:1
93
86
50
92
90
85
78
92
86
93
85
2. Results and discussion
2.5:1
2.6:1
10:1
10:1
5:1
3.2:1
2.7:1
3:1
A representative succinimide-derived pronucleophile 4 was
synthesized in two steps from commercially available succinimide.
The n-butyl group was arbitrarily chosen as a blocking group for
the acidic NH. Initial feasibility and catalyst identification studies
were performed on nitro olefin 3a (Scheme 2) catalysed by a range
of cinchonine derived organocatalysts 1, prepared by reaction of 9-
epi-aminocinchonine (9-EACN) 2 with an iso(thio)cyanide or sulfo-
nylchloride (Scheme 1 and Section 4).
9
10
11
1j
1k
2.7:1
4:1
a
Reaction was carried out with 4 (1.0 equiv), 3a (1.5 equiv) and 1a–k (0.1 equiv)
In a series of experiments, the starting materials were dissolved
in dichloromethane, cooled to ꢀ20 °C and the solid catalysts 1a–k
added directly in one portion. After 24 h the chilled reaction mix-
ture was passed through a plug of silica gel to remove the catalyst,
and on concentrating in vacuo, the reaction conversion was mea-
sured by 1H NMR analysis. Following the chromatographic separa-
tion of the diastereoisomers, the enantiomeric excess of the major
diastereoisomer was measured by HPLC analysis. The results are
presented in Table 1.
in CH2Cl2 (0.16 M in 4).
b
Determined by 1H NMR after 24 h.
c
ee of major diastereoisomer determined 5a by HPLC analysis.
diastereoselectivity, conversion and enantiocontrol. On closer
inspection, the (thio)urea catalysts bearing an N-aryl group gener-
ally outperformed the sulfonamide catalysts 1d and 1e on the basis
of reactivity. However the reaction diastereoselectivity was nota-
bly higher (10:1 dr) with catalysts 1d and 1e compared to ꢁ3:1
dr with the thiourea catalysts 1a–c and 1g–k (although the two
At first glance, all of the catalysts, with the exception of the C2-
symmetric dimeric catalyst 1c, performed well in relation to the
O
O
O
Ph
NO2
3a (1.5 eq.)
Ph
Ph
NO2
COOMe
NO2
COOMe
BuN
O
BuN
O
BuN
O
+
COOMe
1 (0.1 eq.)
-20 °C, 24h
5a
6a
4
Scheme 2.

P. Jakubec et al. / Tetrahedron: Asymmetry 22 (2011) 1147–1155
1149
NO2
O
O
O
Ar
Ar
Ar
NO2
NO2
3a-g (1.5 eq.)
COOMe
BuN
O
BuN
O
BuN
O
+
COOMe
COOMe
1a (0.1 eq.)
-20 °C, 48h
5a-g
6a-g
4
Scheme 3.
Table 2
Scope of the Michael addition of C-succinimidyl ester 4 to nitrostyrenes 3a–g
Entry
Adducts
Ar
Timea (h)
Yieldb (%)
drc
eed maj (%)
eed min (%)
1
2
3
4
5
6
7
5a, 6a
5b, 6b
5c, 6c
5d, 6d
5e, 6e
5f, 6f
Ph
48
48
48
48
48
48
48
81
88
85
84
78
90
96
1.9:1
94
95
96
91
96
94
95
89
90
87
84
91
91
90
2-Br-Ph
2-Cl-Ph
4-Tolyl
3-MeO-Ph
2-Furyl
2-Naphthyl
4.1:1
4.5:1
2.2:1
3.5:1
1.5:1
2.1:1
5g, 6g
a
b
c
Reactions were carried out with 4 (1.0 equiv), 3a–g (1.5 equiv) and 1a (0.1 equiv) in CH2Cl2 (0.16 M in 4).
Isolated yield.
Determined from the amount of separated 5 and 6 after column chromatography.
Determined by HPLC analysis.
d
diastereoisomers were easily separable by silica gel chromatogra-
phy). The highest enantioselectivity of 93% was obtained with
thioureas 1a and 1j. On the basis of the highest reactivity and
enantiocontrol, catalyst 1a, already shown to be optimal for the
addition of dimethyl malonate Michael additions3a and also for
Mannich reactions,1b was selected as the champion. Next, the
scope of the reaction with 4 was investigated by probing changes
to the Michael acceptor 3 (Scheme 3, Table 2).
For a range of aromatic and heteroaromatic nitro olefins 3a–g,
high enantioselectivities (91–96% ee for the major diastereoisomer,
84–91% ee for the minor diastereoisomer), high yields and moder-
ate diastereoselectivities (dr 2.2:1–4.25:1) were obtained after
48 h at ꢀ20 °C. In all cases the diastereoisomers were easily sepa-
rated by flash column chromatography.
reochemistry of the all other adducts 5 and 6 were assigned by
analogy.
Epimeric at the quaternary, but not the tertiary stereogenic cen-
tre, these structural data imply that the thiourea organocatalyst
provides excellent control to the Re-face of the nitro olefin on addi-
tion of the enolised pronucleophile. Furthermore, the chiral pocket
offered by the catalyst is of sufficient size to preferentially enve-
lope one enantiomer of both diastereoisomers and thus similar lev-
els of enantioselectivity are observed in both diastereoisomers.
The relatively high reactivity of C-succinimidyl ester 4 as a pro-
nucleophile prompted us to investigate the level of catalyst loading
that could be tolerated. In a one off experiment the reaction of 4
and 3a catalysed by 1 mol % of 1a was performed. The reaction
was complete after 4 days at ꢀ20 °C and afforded 5a and 6a as a
3.4:1 mixture of diastereoisomers in 79% yield. The enantiomeric
excess of the major diastereoisomer was 97% and that of the minor
diastereoisomer was 91%. These data are similar to those obtained
when the reaction was performed at 10 mol % catalysts loading.
The absolute and relative stereochemical configuration of these
adducts was established by single crystal X-ray diffraction of the
two diastereoisomeric adducts 5b and 6b (Fig. 2). The major enan-
tiomer of the major diastereoisomer was found to be (S,R)-5b, the
major enantiomer of the minor diastereoisomer (R,R)-6b. The ste-
3. Conclusion
In conclusion, we have successfully demonstrated that a prochi-
ral pronucleophile derived from N-butyl C-succinimidyl ester 4 can
be employed in highly stereoselective organocatalysed Michael
addition reactions with a range of nitro olefins, affording adducts
bearing contiguous quaternary and tertiary stereocentres. The
screening of a library of catalysts based on the 9-amino(9-deoxy)
epicinchonine scaffold allowed the identification of the best cata-
lyst, thiourea 1a (although a number of those screened performed
nearly as well). The synthetic utility of the generated adducts, their
further manipulation and the application of these reactions in nat-
ural product synthesis is ongoing.
O
Br
NO2
BuN
O
COOMe
5b
4. Experimental
O
Br
NO2
All reactions conducted under anhydrous conditions glassware
was dried in an oven at 100 °C and carried out under a nitrogen
atmosphere, unless otherwise stated.
Bulk solutions were evaporated under reduced pressure using a
Büchi rotary evaporator. Reagents used were obtained from com-
mercial suppliers or purified according to standard procedures.
Petrol refers to distilled light petroleum of fraction (40–65 °C).
BuN
O
COOMe
6b
Figure 2. Single crystal X-ray determination of absolute and relative stereochem-
ical configurations of 5b and 6b.

1150
P. Jakubec et al. / Tetrahedron: Asymmetry 22 (2011) 1147–1155
Anhydrous tetrahydrofuran and diethyl ether were freshly distilled
from sodium-benzophenone.
52.0, 49.0, 46.0, 38.6, 27.1, 26.4, 24.1; MS m/z (ES+) 434 (100%,
MH+). [HR-MS (ES+): MH+, 434.1906. [C25H28N3O2S]+ requires
Flash column chromatography was performed with commercial
solvents using Merck Kieselgel 60 silica gel (200–400 mesh). Thin
layer chromatography (TLC) was performed on aluminium or glass
plates pre-coated with Merck Kieselgel 60 F254 and visualised by
ultra-violet radiation or by staining with either aqueous basic
potassium permanganate or vanillin. Enantiomeric excesses were
determined using high performance liquid chromatography (HPLC)
performed on a Hewlett-Packard Series 1050 series system (col-
umn conditions are given with the compound).
434.1897]; ½a 2D0
¼ þ67 (c 1.00, CHCl3).
ꢂ
4.2. 1-(3,5-Bis(trifluoromethyl)phenyl)-3-[(R)-(quinolin-4-
yl)((2R,4S,5R)-5-vinylquinuclidin-2-yl)methyl]urea 1f
A solution of 9-amino(9-deoxy) epicinchonine2a,2p (448 mg,
1.53 mmol) in dry THF (1 mL/0.17 mmol) was added slowly to
bis(trifluoromethyl)isocyanate (291 lL, 1.68 mmol) in dry THF
(1 mL/0.19 mmol) at 0 °C. The reaction mixture was allowed to
warm to rt and stirred for 3 h until analysis by TLC indicated that
all of the amine had been consumed. Purification by flash column
chromatography [EtOAc/MeOH/Et3N (100:2:3–100:10:3) afforded
catalyst 1h as a colourless solid (629 mg, 75% yield). Mp 200–
Melting points were recorded on a Gallenkamp melting point
apparatus with the sample contained in a thin glass tube at ambi-
ent pressure and are uncorrected.
Optical rotations were recorded using an Optical Activity AA-
1000 polarimeter; specific rotations ([
10ꢀ1 deg cm2 gꢀ1; concentrations (c) are quoted in g (100 mL)ꢀ1
D refers to the -line of sodium (589 nm); temperatures (T) are gi-
ven in degrees Celsius (°C).
a
]D) are reported in
204 °C; IR m
max(film)/cmꢀ1 2937 (N–H), 1678 (C@O), 1594 and
;
1551 (C@C); 1H NMR (500 MHz, CD3OD) dH 8.83 (d, 1H, J = 4.7,
Ar-H), 8.50 (d, 1H, J = 8.4, Ar-H), 8.06 (d, 1H, J = 7.9, Ar-H), 7.89 (s,
2H, Ar-H), 7.76 (t, 1H, J = 7.6, Ar-H), 7.68 (t, 1H, J = 7.6, Ar-H),
7.62 (d, 1H, J = 4.7, Ar-H), 7.41 (s, 1H, Ar-H), 5.89 (ddd, 1H,
J = 17.1, 10.5, 6.4, CH2@CH), 5.62 (br s, 1H, NH–CH), 5.15–5.11
(m, 2H, CH2@CH), 3.21 (dd, 1H, J = 18.5, 9.0, CH–N), 3.12 (dd, 1H,
J = 13.5, 7.5, CH–N), 3.05–2.95 (m, 3H, CH–N), 2.29 (dd, 1H,
J = 15.8, 7.7, quinuclidine-H), 1.58–1.53 (m, 3H, quinuclidine-H),
1.21–1.17 (m, 1H, quinuclidine-H), 0.96–0.93 (m, 1H, quinucli-
dine-H); 13C NMR (125 MHz, CD3OD) dC 156.7, 151.0, 149.1,
143.2, 141.5, 133.1 (q, J = 33, 2ꢃ Ar), 131.0, 130.1, 128.8, 128.2,
125.5 (q, J = 272, 2 ꢃ CF3), 125.0, 119.0, 119.0, 115.5 (br q, J = 4,
3 ꢃ Ar), 115.3, 61.3, 61.2, 50.2, 48.1, 40.5, 28.9, 27.4, 26.4; MS m/
D
Infrared spectra were recorded on a Perkin Elmer Spectrum RX1
FTIR spectrometer (thin film deposited onto a sodium chloride
plate). Only selected absorbencies (mmax) are reported.
1H, 13C, DEPT, COSY and HMQC NMR spectra were recorded on
Bruker 500 MHz and Varian 300 MHz spectrometers. Chemical
shifts (dH) are quoted in parts per million (ppm 0.01 ppm) down-
field of tetramethylsilane, relative to the residual protiosolvent (dH
(CHCl3) = 7.26 ppm) against an internal deuterium lock. Coupling
constants (J) are given in Hertz (Hz 0.1 Hz). The 1H NMR spectra
are reported as follows: d/ppm (multiplicity, number of protons,
coupling constants J/Hz, assignment). DEPT and two-dimensional
NMR spectroscopy (COSY and HMQC) were used where appropri-
ate to assist the assignment of the signals in the 1H NMR and 13C
NMR spectra.
z
(ES+) 549 (98%, MH+). [HR-MS (ES+): MH+, 549.2097.
[C28H27N4OF6]+ requires 549.2089]; ½a 2D0
¼ þ134:0 (c 1.00, CHCl3).
ꢂ
4.3. General method A for the synthesis of catalysts 1g–k
Low resolution mass spectrometry (electron impact/chemical
ionisation) was recorded on a Micromass Trio 2000 quadropole
mass spectrometer and (electrospray) on a Micromass Platform II
spectrometer. High resolution mass spectra (accurate mass) were
recorded on a Thermo Finnigan Mat95XP mass spectrometer.
N-Butylsuccinimide and nitro olefins 3a, 3f are commercially
available, compounds 1a (Mp 186–189 °C), 1b–d3a were prepared
according to literature procedures.
A solution of amine 2 in dry THF (1 mL/0.17 mmol) was added
slowly to the isothiocyanate (1.1 equiv) in dry THF (1 mL/
0.19 mmol) at 0 °C. The reaction mixture was allowed to warm to
rt and stirred until analysis by TLC indicated that all of the amine
had been consumed. Purification by flash column chromatography
on silica gel [EtOAc/MeOH/Et3N (100:2:3–100:10:3) or Et2O/
MeOH/Et3N (100:10:0–90:10:10)] afforded the title organocatalyst
1g–k.
4.1. N-[(9R)-Cinchonan-9-yl]benzenesulfonamide 1e
4.4. 1-[(9R)-Cinchonan-9-yl]-3-(2-methoxyphenyl)thiourea 1g
9-Amino(9-deoxy) epicinchonine2a,2p (703 mg, 2.4 mmol) and
Following general method A using amine 2 (340 mg, 1.2 mmol)
Et3N (668
l
L, 4.8 mmol) were dissolved in dry DCM (30 mL) and
and 2-methoxyphenyl isothiocyanate (232 mg, 194
the title compound 1g (488 mg, 92% yield) was obtained as a white
solid. Mp 105–109 °C; IR
max(film)/cmꢀ1 2938, 2872, 1509; 1H
lL, 1.4 mmol),
cooled to 0 °C. Benzenesulfonyl chloride (458
lL, 3.6 mmol) in
dry DCM (15 mL) was added. The reaction mixture was allowed
to warm to rt and stirred for 20 h until analysis by TLC indicated
that all of the amine had been consumed. Purification by flash col-
umn chromatography [EtOAc/MeOH/Et3N (300:5:1) afforded cata-
lyst 1e as a colourless solid (659 mg, 63% yield). Mp 139–144 °C; IR
m
NMR (500 MHz, CD3OD) dH 8.72 (d, 1H, J = 4.7, Ar-H), 8.61 (d, 1H,
J = 8.5, Ar-H), 8.02 (dd, 1H, J = 8.5, 0.6, Ar-H), 7.82 (br d, 1H,
J = 7.9, Ar-H), 7.75–7.72 (m, 1H, Ar-H), 7.65–7.62 (m, 1H, Ar-H),
7.49 (d, 1H, J = 4.7, Ar-H), 7.09 (td, 1H, J = 7.9, 1.6, Ar-H), 6.93–
6.92 (m, 1H, Ar-H), 6.85 (td, 1H, J = 7.7, 1.3, Ar-H), 6.19 (br d, 1H,
J = 10.1, NH–CH), 5.90 (ddd, 1H, J = 17.2, 10.6, 6.3, CH2@CH),
5.18–5.14 (m, 2H, CH2@CH), 3.67 (s, 3H, CH3O), 3.16–3.10 (m, 2H,
CH–N), 2.95–2.78 (m, 3H, CH–N), 2.27 (‘q’, 1H, J = 7.8, quinucli-
dine-H), 1.49–1.40 (m, 3H, quinuclidine-H), 1.22–1.17 (m, 1H,
quinuclidine-H), 0.76–0.71 (m, 1 H, quinuclidine-H); 13C NMR
(125 MHz, CD3OD) dC 182.2, 153.4, 151.0, 150.6, 148.9, 141.7,
131.0, 129.9, 129.2, 128.6, 127,9, 127.4, 126.3, 126.2, 121.4,
121.1, 115.4, 112.4, 61.9, 56.3, 56.3, 50.0, 48.4, 40.5, 28.9, 27.4,
26.2; MS m/z (ES+) 459 (100%, MH+). [HR-MS (ES+): MH+,
m
max(film)/cmꢀ1 3629 (H), 3070, 2937, 2863 (CH), 1166 (SO2); 1H
NMR (400 MHz, CD3OD) dH ppm: 8.59–8.50 (m, 1H, Ar-H), 8.04
(d, 1H, J = 6.6, Ar-H), 7.88 (d, 1H, J = 8.4, Ar-H), 7.72–7.63 (m, 1H,
Ar-H), 7.62–7.53 (m, 1H, Ar-H), 7.50–7.33 (m, 3H, Ar-H), 7.28 (t,
1H, J = 7.5, Ar-H), 7.18–7.07 (m, 2H, Ar-H), 5.74–5.63 (m, 1H,
CH2 = CH), 5.06–4.74 (m, 3H, CH2 = CH and CHNH), 2.97–2.75 (m,
3H, quinuclidine-H), 2.75–2.63 (m, 1H, quinuclidine-H), 2.50–
2.38 (m, 1H, quinuclidine-H), 2.13 (d, 1H, J = 6.1, quinuclidine-H),
1.50–1.30 (m, 3H, quinuclidine-H), 1.00–0.86 (m, 1H, quinucli-
dine-H), 0.70–0.60 (m, 1H, quinuclidine-H); 13C NMR (125 MHz,
CD3OD) dC 149.9, 148.9, 145.0, 140.1, 139.1, 132.7, 130.5, 129.1,
128.6, 128.1, 127.7, 127.4, 127.3, 126.8, 122.2, 120.1, 114.7, 61.6,
459.2193. [C27H31ON4S]+ requires 459.2213]; ½a 2D5
¼ þ322:5 (c
ꢂ
0.08, CHCl3).

P. Jakubec et al. / Tetrahedron: Asymmetry 22 (2011) 1147–1155
1151
4.5. 1-[(9R)-Cinchonan-9-yl]-3-(3-methylphenyl)thiourea 1h
4.8. 1-[(9R)-Cinchonan-9-yl]-3-dodecylthiourea 1k
Following general method using amine
Following general method
0.75 mmol) and 3-methylphenyl isothiocyanate (123 mg, 112
0.82 mmol), the title compound 1h (301 mg, 91% yield) was ob-
tained as a white solid. Mp 102–106 °C; IR
max(film)/cmꢀ1 2938,
A
using amine
2
(220 mg,
A
2
(220 mg,
lL,
0.75 mmol) and dodecyl isothiocyanate (207 mg (90% pure),
0.82 mmol), the title compound 1k (273 mg, 82% yield) was ob-
m
tained as an white solid solid. Mp 57–60 °C; IR m
max(film)/cmꢀ1
2870, 1509 1H NMR (500 MHz, CD3OD) dH 8.74 (d, 1H, J = 4.7, Ar-
H), 8.61 (d, 1H, J = 8.5, Ar-H), 8.03 (dd, 1H, J = 8.5, 0.6, Ar-H), 7.75
(dt, 1H, J = 7.7, 1.3, Ar-H), 7.66–7.63 (m, 1H, Ar-H), 7.51 (d, 1H,
J = 4.7, Ar-H), 7.19–7.14 (m, 2H, Ar-H), 7.09 (br d, 1H J = 7.6, Ar-
H), 6.96 (d, 1H, J = 7.6, Ar-H), 6.19 (br d, 1H, J = 10.4, NH–CH),
5.97–5.90 (m, 1H, CH2@CH), 5.20–5.16 (m, 2H, CH2@CH), 3.16–
3.13 (m, 2H, CH–N), 3.00–2.86 (m, 3H, CH–N), 2.32–2.27 (m, 1H,
quinuclidine-H), 2.27 (s, 3H, CH3Ar), 1.52–1.42 (m, 3H, quinucli-
dine-H), 1.26–1.22 (m, 1H, quinuclidine-H), 0.81–0.75 (m, 1H,
quinuclidine-H); 13C NMR (125 MHz, CD3OD) dC 182.1, 151.0,
150.5, 149.0, 141.7, 140.3, 139.7, 131.0, 130.1, 129.9, 129.1,
127.9, 127.4, 126.1, 125.7, 122.2, 121.1, 115.5, 61.9, 56.5, 50.0,
48.4, 40.5, 29.0, 27.4, 26.2, 21.7; MS m/z (ES+) 443 (100%, MH+).
[HR-MS (ES+): MH+, 443.2257. [C27H31N4S]+ requires 443.2264];
2923, 2853, 1509; 1H NMR (500 MHz, CD3OD) dH 8.77 (d, 1H,
J = 4.8, Ar-H), 8.66 (d, 1H, J = 8.1, Ar-H), 8.03 (dd, 1H, J = 8.5, 0.9,
Ar-H), 7.74 (td, 1H, J = 7.6, 1.0, Ar-H), 7.66–7.62 (m, 1H, Ar-H),
7.54 (br s, 1H, Ar-H), 6.21 (br s, 1H, ⁄C–H), 5.91 (ddd, 1H, J = 17.2,
10.6, 6.3, CH2@CH), 5.21–5.14 (m, 2H, CH2@CH), 3.36–3.25 (m.
2H, NHCH2CH2), 3.21–3.05 (m, 2H, CH–N), 2.99–2.85 (m, 3H, CH–
N), 2.28 (‘q’, 1H, J = 7.6, quinuclidine-H), 1.51–1.39 (m, 5H, 3H of
quinuclidine-H, 1 ꢃ CH2 of NHCH2(CH2)10CH3), 1.31–1.20 (m,
19H, 1H of quinuclidine-H, 9 ꢃ CH2 of NHCH2(CH2)10CH3)), 0.88
(t, 3H, J = 7.0, CH2CH3), 0.79–0.74 (m, 1H, quinuclidine-H); 13C
NMR (125 MHz, CD3OD) dC 182.2, 150.9, 150.9, 149.0, 141.6,
131.9, 129.9, 129.1, 127.9, 126.3, 121.1, 115.5, 61.9, 56.0, 50.1,
48.4, 45.5, 40.5, 33.2, 30.9, 30.9, 30.8, 30.8, 30.6, 30.6, 30.2, 29.0,
28.1, 27.4, 26.3, 23.9, 14.7; MS m/z (ES+) 521 (100%, MH+). [HR-
MS (ES+): MH+, 521.3672. [C26H28O2N5S]+ requires 521.3655];
½
a 2D5
ꢂ
¼ þ317:0 (c 0.11, CHCl3).
½
a 2D5
ꢂ
¼ þ195:1 (c 0.12, CHCl3).
4.6. 1-[(9R)-Cinchonan-9-yl]-3-(4-nitrophenyl)thiourea 1i
4.9. General method B for the synthesis of nitro olefins 3b–e, g
Following general method
1.47 mmol), the title compound 1i (624 mg, 90% yield) was ob-
tained as an orange solid. Mp 148–154 °C; IR
max(film)/cmꢀ1
A
using amine
2
(430 mg,
According to the modified literature procedure.6 To a stirred
solution of the aryl aldehyde and nitromethane (10 equiv) was
added ammonium acetate (1.1 equiv). The solution was heated at
reflux for 24 h. The reaction mixture was concentrated in vacuo
and then dissolved in CH2Cl2/H2O (1:1), the organics were ex-
tracted into CH2Cl2 (3ꢃ), then washed with brine, dried (magne-
sium sulfate), filtered and concentrated in vacuo. Purification by
flash column chromatography on silica gel [EtOAc/petroleum
ether] afforded the title nitro olefin.
m
2936 (N-H), 1596 and 1549 (C@C), 1507 and 1328 (N–O and
C@S); 1H NMR (500 MHz, CD3OD) dH 8.78 (d, 1H, J = 4.7, Ar-H),
8.59 (d, 1H, J = 8.4, Ar-H), 8.14–8.07 (m, 2H, Ar-H), 8.01 (dd,
J = 8.5, 0.9, 1H, Ar-H), 7.77–7.72 (m, 3H, Ar-H), 7.65 (ddd, 1H,
J = 8.3, 6.9, 1.2, Ar-H), 7.57 (d, 1H, J = 4.7, Ar-H), 6.22 (br d, 1H,
J = 9.4, NH–CH), 5.92 (ddd, 1H, J = 17.1, 10.6, 6.3, CH2@CH), 5.20–
5.13 (m, 2H, CH2@CH), 3.25–3.23 (m, 1H, CH–N), 3.14 (br dd, 1H,
J = 13.8, 7.0, CH–N), 2.99–2.96 (m, 3H, CH–N), 2.33 (br d, 1H,
J = 15.7, 7.8, quinuclidine-H), 1.57–1.52 (m, 3H, quinuclidine-H),
1.27–1.20 (m, 1H, quinuclidine-H), 0.89–0.82 (m, 1H, quinucli-
dine-H); 13C NMR (125 MHz, CD3OD) dC 181.9, 150.9, 149.9,
148.9, 147.3, 144.2, 141.5, 131.0, 129.9, 129.0, 127.9, 125.9, 125.3
(2 ꢃ C), 122.0 (2 ꢃ C), 120.9, 115.4, 61.9, 61.5, 50.0, 48.4, 40.4,
28.8, 27.3, 26.1; MS m/z (ES+) 474 (100%, MH+). [HR-MS (ES+):
4.10. 1-Bromo-2-[(E)-2-nitroethenyl]benzene 3b
Following general method B, the title compound 3b (1.49 g, 47%
yield) was obtained as a yellow solid after flash column chroma-
tography on silica gel [EtOAc/petroleum ether (1:8–1:2)]. Mp 82–
87 °C, lit.7a 88–91 °C; lit.7b 86 °C; IR max(film)/cmꢀ1 1632 (C@C),
m
MH+,
474.1964.
[C26H28O2N5S]+
requires
474.1958];
1561 and 1339 (N–O), 970 (C@C); 1H NMR (500 MHz, CDCl3) dH
8.43 (d, 1H, J = 13.6, CH@CHNO2), 7.72 (dd, 1H, J = 7.8, 1.3, Ar-H),
7.60 (dd, 1H, J = 7.8, 1.8, Ar-H), 7.57 (d, 1H, J = 13.6, @CH–NO2),
7.42 (dt, 1H, J = 7.6, 1.3, Ar-H), 7.37 (dt, 1H, J = 7.6, 1.8, Ar-H); 13C
NMR (125 MHz, CDCl3) dC 139.2 (CH@CHNO2), 138.0 (CH@CHNO2),
134.4 (Ar:Cquat), 133.4 (Ar), 130.8 (Ar), 128.9 (Ar), 128.5 (Ar), 126.8
(Ar:Cortho-Br); MS m/z (CI+) 245 (100%, MNH4þ), 247 (100%,
MNH4þ). [HR-MS (ES+): MNH4þ, 244.9915. [C8H10BrN2O2]+ re-
quires 244.9920].
½ ꢂ
a 2D0
¼ þ216:7 (c 1.00, CHCl3).
4.7. 1-[(9R)-Cinchonan-9-yl]-3-(4-methoxyphenyl)thiourea 1j
Following general method
1.18 mmol), the title compound 1j (406 mg, 75% yield) was ob-
tained as a colourless solid. Mp 117–119 °C; IR
max(film)/cmꢀ1
A
using amine
2
(346 mg,
m
2938, 1595, 1532, 1509; 1H NMR (500 MHz, CD3OD) dH 8.71 (d,
1H, J = 4.6, Ar-H), 8.56 (d, 1H, J = 8.3, Ar-H), 7.97 (d, 1H, J = 8.3,
Ar-H), 7.71 (t, 1H, J = 7.6, Ar-H), 7.60 (t, 1H, J = 7.6, Ar-H), 7.47 (d,
1H, J = 4.6, Ar-H), 7.13 (d, 2H, J = 8.9, Ar-H), 6.82 (d, 2H, J = 8.9,
Ar-H), 6.14 (br d, 1H, J = 10.5, NH–CH), 5.89 (ddd, 1H, J = 17.1,
10.5, 6.3, CH2@CH), 5.17–5.09 (m, 2H, CH2@CH), 3.71 (s, 3H, Ar-
OCH3), 3.14–3.06 (m, 2H, CH–N), 2.91 (dd, 1H, J = 14.2, 10.1, CH–
N), 2.85 (br t, 2H, J = 7.1, CH–N), 2.26 (br dd, 1H, J = 15.7, 7.6, quinu-
clidine-H), 1.54–1.39 (m, 3H, quinuclidine-H), 1.23–1.15 (m, 1H,
quinuclidine-H), 0.79–0.72 (m, 1H, quinuclidine-H); 13C NMR
(75 MHz, CD3OD) dC 182.5, 159.2, 150.9, 150.4, 148.8, 141.6,
132.2, 130.8, 129.8, 128.9, 127.8, 127.6 (2ꢃ C), 126.0, 125.8,
121.0, 115.3 (2 ꢃ C), 61.7, 56.3, 56.0, 49.9, 48.2, 40.4, 28.8, 27.3,
26.1; MS m/z (ES+) 459 (100%, MH+). [HR-MS (ES+): MH+,
4.11. 1-Chloro-2-[(E)-2-nitroethenyl]benzene 3c
Following general method B, the title compound 3c (936 mg, 73%
yield) was obtained as a yellow solid after flash chromatography
[EtOAc/petroleum ether (1:6–1:3). Mp 45–48 °C, lit.8a 48 °C, lit.8b
42–43 °C; IR m
max(film)/cmꢀ1 1630 (C@C), 1529 and 1375 (N–O),
963 (C@C); 1H NMR (500 MHz, CDCl3) dH 8.44 (d, 1H, J = 13.7,
CH@CHNO2), 7.63 (d, 1H, J = 13.7, @CH–NO2), 7.62 (dd, 1H, J = 7.7,
1.7, Ar-H), 7.53 (dd, 1H, J = 8.0, 1.0, Ar-H), 7.46 (dt, 1H, J = 7.7, 1.7,
Ar-H), 7.37 (ddd, 1H, J = 8.0, 7.7, 1.0, Ar-H); 13C NMR (125 MHz,
CDCl3) dC 139.2 (CH@CHNO2), 136.5 (CH@CHNO2), 135.5 (Ar:Cquat),
133.3 (Ar-CH), 131.2 (Ar:Cortho-Cl), 129.0, 128.9, 127.9 (Ar-C); MS
m/z (CI+) 201 (37%, MNH4þ), 203 (12%, MNH4þ). [HR-MS (ES+):
MNH4þ, 201.0430. [C8H10ClN2O2]+ requires 201.0425].
459.2214. [C27H31ON4S]+ requires 459.2213]; ½a 2D4
¼ þ303:4 (c
ꢂ
1.30, CHCl3).

1152
P. Jakubec et al. / Tetrahedron: Asymmetry 22 (2011) 1147–1155
4.12. 1-Methyl-4-[(E)-2-nitroethenyl]benzene 3d
(CH3O), 45.9 (CH2N), 39.0 (CHC(O)N), 31.9 (CH2CH2N), 29.3
(CH2C(O)N), 19.7 (CH3CH2), 13.3 (CH3CH2); MS m/z (ES+) 227
(30%, MNH4þ); [HR-MS (EI+): M, 213.0989. [C10H15NO4]+ requires
213.0996].
Following general method B, the title compound 3d (1.79 g, 78%
yield) was obtained as a yellow solid after flash column chroma-
tography on silica gel [EtOAc/petroleum ether (1:8–1:4)]. Mp
106–109 °C, lit.8a 101–102 °C, lit.9 104.5–105 °C; IR
mmax(film)/
4.16. General method C for the organocatalysed Michael
addition of succinimide 4 to nitro olefins 3
cmꢀ1 1630 (C@C), 1560 and 1377 (N–O), 963 (C@C); 1H NMR
(500 MHz, CDCl3) dH 7.90 (d, 1H, J = 13.6, CH@CHNO2), 7.49 (d,
1H, J = 13.6, @CH–NO2), 7.36 (d, 2H, J = 8.1, Ar-H), 7.18 (d, 2H,
J = 8.1, Ar-H), 2.33 (s, 3H, Ar-CH3); 13C NMR (125 MHz, CDCl3) dC
143.6 (Ar:Cpara–CH3), 139.7 (CH@CHNO2), 136.7 (CH@CHNO2),
130.6 (Ar:Cquat), 129.6 (2 ꢃ Ar), 127.7 (2 ꢃ Ar-C), 22.1 (Ar-CH3);
MS m/z (CI+) 181 (100%, MNH4þ); [HR-MS (ES+): M+,163.0630.
[C9H9NO2]+ requires 163.0628].
To a stirred solution of nitro olefin 3 (0.493 mmol) and succin-
imide 4 (70 mg, 0.329 mmol) in dry CH2Cl2 (2.0 mL) was added cat-
alyst 1 (0.0329 mmol). The reaction was stirred at ꢀ20 °C until
analysis by TLC indicated that all of the succinimide had been con-
sumed (48 h). The solution was then filtered through a plug of sil-
ica, concentrated, and analysed by 1H NMR before purification by
flash column chromatography [Et2O/petroleum ether (1:1)] to
yield the desired adducts 5 and 6 as chromatographically separable
diastereoisomers.
4.13. 1-Methoxy-3-[(E)-2-nitroethenyl]benzene 3e
Following general method B, the title compound 3e (2.57 g, 99%
yield) was obtained as a yellow solid after flash silica gel chroma-
tography [EtOAc/petroleum ether (1:4–1:1)]. Mp 89–91 °C, lit.8b
4.17. (S)-Methyl 1-butyl-3-((S)-2-nitro-1-phenylethyl)-2,5-
dioxopyrrolidine-3-carboxylate 4a and (R)-methyl 1-butyl-3-
((S)-2-nitro-1-phenylethyl)-2,5-dioxopyrrolidine-3-carboxylate
5a
89–9 l °C, lit.10 91–92 °C; IR
m
max(film)/cmꢀ1 1638 (C@C), 1577
and 1377 (N–O), 962 (C@C); 1H NMR (500 MHz, CDCl3) dH 8.01
(d, 1H, J = 13.7, CH@CHNO2), 7.60 (d, 1H, J = 13.7, @CH–NO2), 7.40
(dd, 1H, J = 9.0, 7.7, Ar-H), 7.18 (d, 1H, J = 7.7, Ar-H), 7.12–7.06
(m, 2H, Ar-H), 3.88 (s, 3H, OCH3); 13C NMR (125 MHz, CDCl3) dC
160.5 (Ar:Cmeta–OCH3), 139.5 (CH@CHNO2), 137.8 (CH@CHNO2),
Following the general method C, the title compounds 5a (63 mg,
53% yield) and 6a (33 mg, 28% yield) were obtained after 48 h as
colourless solids in 94% ee (5a) [Chiralpak 1B, Hexane/IPA 85:15,
1.0 mL/min, k 215 nm, t (major) = 11.7 min, t (minor) = 16 min])
and 89% ee (6a) [Chiralpak IB, Hexanes/IPA 85:15, 1.0 mL/min, k
215 nm, t (major) = 16.3 min, t (minor) = 21.3 min] as determined
by HPLC analysis.
131.7 (Ar:Cquat), 130.9, 122.2, 118.4, 114.4 (Ar-C), 55.9 (Ar-
þ
OCH3); MS m/z (CI+) 197 (78%, MNH4þ). [HR-MS (ES+): MNH4
,
197.0926. [C9H13N2O3]+ requires 197.0921].
Data for 5a: Mp 83–86 °C; IR m
max(film)/cmꢀ1 2958 (CH), 1743
4.14. 2-[(E)-2-Nitroethenyl]naphthalene 3g
(C@O), 1705 (C@O), 1557 (C@O); 1H NMR (500 MHz, CDCl3) dH
7.30 (m, 3H, Ar-H), 7.15 (m, 2H, Ar-H), 5.29 (dd, 1H, J = 13.9, 10.9,
CHAHB–NO2), 5.11 (dd, 1H, J = 13.9, 3.38, CHAHB-NO2), 4.25 (dd,
1H, J = 10.9, 3.38, Ar-⁄CH), 3.81 (s, 3H, CH3O), 3.44 (m, 2H, CH2N),
2.82 (d, 1H, J = 18.3, CH2C(O)N), 2.64 (d, 1H, J = 18.3, CH2C(O)N),
1.53–1.39 (m, 2H, CH2CH2N), 1.21 (m, 2H, CH3CH2CH2), 0.90 (t,
3H, J = 7.4, 7.4, CH3CH2); 13C NMR (125 MHz, CDCl3) dC 174.1
(C@O), 173.4 (C@O), 168.7 (C@O), 139.3, 130.3, 130.2, 129.0 (Ar-
C), 76.1 (CH2NO2), 57.9 (quaternary C), 54.2 (OCH3), 45.6 (CH2N),
39.5 (NO2CH2CH), 35.3 (CH2C(O)N), 29.3 (CH2CH2N), 19.9
(CH3CH2), 13.8 (CH3CH2); MS m/z (CI+) 380 (40%, MNH4þ). [HR-
MS (ES+): MNH4þ, 380.1814. [C18H26O6N3]+ requires 380.1816];
Following general method B, the title compound 3g (2.07 g,
74% yield) was obtained as a yellow solid after flash column chro-
matography on silica gel [EtOAc/petroleum ether (1:4–1:3)]. Mp
128–131 °C, lit.11 120–121 °C; IR
m
max(film)/cmꢀ1 1629 (C@C),
1535 and 1377 (N–O), 964 (C@C); 1H NMR (500 MHz, CDCl3) dH
8.21 (d, 1H, J = 13.6, CH@CHNO2), 8.06 (s, 1H, Ar-H), 7.93–7.91
(m, 3H, Ar-H), 7.74 (d, 1H, J = 13.6, @CH–NO2), 7.65–7.62 (m,
3H, Ar-H); 13C NMR (125 MHz, CDCl3) dC 139.7 (Ar), 137.6 (Ar),
135.3 (Ar:Cquat), 133.6 (Ar:Cquat), 132.7, 129.8, 129.3, 128.8,
128.4 (Ar-C), 128.0 (Ar:Cquat), 127.7, 123.7 (Ar-C); MS m/z (CI+)
217 (100%, MNH4þ). [HR-MS (ES+): M+, 199.0625. [C12H9NO2]+ re-
quires 199.0628].
½
a 2D5
ꢂ
¼ þ89 (c 0.7, CHCl3).
Data for 6a: Mp 84–88 °C; IR
v
max(film)/cmꢀ1 2958 (CH), 1744
(C@O), 1706 (C@O), 1557 (C@O); 1H NMR (500 MHz, CDCl3) dH
7.32–7.28 (m, 3H, Ar-H), 7.25–7.22 (m, 2H, Ar-H), 5.13 (dd, 1H,
J = 13.4, 4.3, CHAHB-NO2), 4.95 (dd, 1H, J = 13.4, 10.6, CHAHB-NO2),
4.51 (dd, 1H, J = 10.6, 4.3, Ar-⁄CH), 3.84 (s, 3H, CH3O), 3.27 (t, 2H,
J = 7.5, CH2N), 3.18 (d, 1H, J = 18.3, CH2C(O)N), 2.83 (d, 1H,
J = 18.2, CH2C(O)N), 1.13 (m, 2H, CH2CH2N), 1.06–0.90 (m, 2H,
CH3CH2CH2), 0.79 (t, 3H, J = 7.3, CH3CH2) 13C NMR (125 MHz,
CDCl3) dC 173.8 (C@O), 173.2 (C@O), 168.5 (C@O), 133.4, 129.3,
129.2, 128.9 (Ar-C), 75.8 (CH2NO2) 57.6 (quaternary C), 54.0
(C@O)OCH3), 45.8 (CH2N), 39.3 (NO2CH2CH), 35.2 (CH2C(O)N),
29.1 (CH2CH2N), 19.7 (CH3CH2), 13.6 (CH3CH2); MS m/z (ES) 385
(100%, MNa+). [HR-MS (ES+): MNa+, 385.1380. [C18H22O6N2Na]+ re-
4.15. Preparation of (rac)-methyl 1-butyl-2,5-dioxopyrrolidine-
3-carboxylate 4
To a solution of n-butylsuccinimide (1.98 g, 12.77 mmol) in THF
(40 mL) at ꢀ78 °C was added lithium hexamethyldisilazide
(25.5 mmol) dropwise as a 1 M solution (THF (25.5 mL)). The solu-
tion was warmed to 0 °C for 30 min before being cooled to ꢀ78 °C.
Methyl chloroformate (0.997 mL, 12.77 mmol) was then added
rapidly and the solution was stirred for 15 minutes at ꢀ78 °C be-
fore being quenched with saturated ammonium chloride solution.
The reaction mixture was warmed to room temperature, extracted
into Et2O and washed with brine After extraction the organics were
dried using MgSO4 and the crude product purified by flash column
chromatography [Et2O/petroleum ether (1:1)] to yield succinimide
quires 385.1370]; ½a D25
¼ ꢀ55 (c 0.3, CHCl3).
ꢂ
4.18. (S)-Methyl 3-((R)-1-(2-bromophenyl)-2-nitroethyl)-1-
butyl-2,5-dioxopyrrolidine-3-carboxylate 5b and (R)-methyl 3-
((R)-1-(2-bromophenyl)-2-nitroethyl)-1-butyl-2,5-dioxopyrroli
dine-3-carboxylate 6b
3 as a colourless oil (1.05 g, 40%); IR mmax(film) 2958 (CH) 1744
(C@O); 1H NMR (500 MHz, CDCl3) dH 3.82 (s, 3H, OCH3), 3.77 (dd,
1 H, J = 9.4, 4.7), 3.5 (m, 2 H, CH2N), 3.1 (dd, 1 H, J = 18.2, 4.7),
2.89 (dd, 1 H, J = 18.2, 9.4), 1.60–1.51 (m, 2 H, CH2CH2N), 1.30
(qd, 2 H, J = 14.8, 7.4, CH2CH3), 0.92 (t, 3 H, J = 7.4, CH3); 13C NMR
(125 MHz, CDCl3) dC 174.8 (C@O), 171.9 (C@O), 167.9 (C@O), 53.1
Following general method C, the title compounds 5b (94 mg,
70% yield) and 6b (23 mg, 18% yield) were obtained after 48 h as

P. Jakubec et al. / Tetrahedron: Asymmetry 22 (2011) 1147–1155
1153
colourless crystals in 95% ee 5b [Chiralpak IB, Hexanes/IPA 85:15,
1.0 mL/min, k 215 nm, t (major) = 18.5 min, t (minor) = 9.9 min]
and 90% ee 6b [Chiralpak IB, Hexanes/IPA 85:15, 1.0 mL/min, k
215 nm, t (major) = 18.8 min, t (minor) = 15.1 min] as determined
by HPLC analysis.
3.4, CHAHB–NO2), 5.10 (dd, 1H, J = 10.9, 3.4, Ar-⁄CH), 3.83 (s, 3H,
CH3O), 3.44 (m, 2H, CH2N), 2.86 (d, 1H, J = 18.6, CH2C(O)N), 2.62
(d, 1H, J = 18.6, CH2C(O)N), 1.46 (m, 2H, CH2CH2N), 1.22 (m, 2H,
CH3CH2CH2), 0.90 (t, 3H, J = 7.3, CH3CH2); 13C NMR (125 MHz,
CDCl3) dC 174.4 (C@O), 173.3 (C@O), 169.3 (C@O), 133.0, 130.8,
130.7, 128.0, (Ar-C), 76.1 (CH2NO2), 57.2 (quaternary C), 53.8
(OCH3), 40.5 (CH2N), 39.1 (NO2CH2CH), 37.3 (CH2C(O)N), 29.1
Data for 5b: Mp 106–109 °C; IR
v
max(film)/cmꢀ1 2959 (CH),
1783 (C@O), 1746 (C@O), 1706 (C@O), 1556; 1H NMR (500 MHz,
CDCl3) dH 7.56 (dd, 1H, J = 8.3, 1.3, Ar-H), 7.18 (m, 1H, Ar-H), 7.10
(m, 2H, Ar-H), 5.25 (dd, 1H, J = 14.2, 10.9, CHAHB-NO2), 5.12 (dd,
1H, J = 14.2, 3.4, CHAHB–NO2), 5.04 (dd, 1H, J = 10.9, 3.4, Ar-⁄CH),
3.78 (s, 3H, CH3O), 3.39 (t, 2H, J = 7.4, CH2N), 2.81 (d, 1H, J = 18.5,
CH2C(O)N), 2.60 (d, 1H, J = 18.6, CH2C(O)N), 1.41 (m, 2H, CH2CH2N),
1.15 (m, 2H, CH3CH2CH2), 0.84 (t, 3H, J = 7.4, CH3CH2); 13C NMR
(125 MHz, CDCl3) dC 174.6 (C@O), 173.4 (C@O), 169.4 (C@O),
134.2, 133.6, 130.5, 128.4, 127.7, 127.6 (Ar-C), 76.4 (CH2NO2),
56.4 (quaternary C), 54.0 (OCH3), 43.4 (CH2N), 39.3 (NO2CH2CH),
37.5 (CH2C(O)N), 29.2 (CH2CH2N), 19.8 (CH3CH2), 13.5 (CH3CH2);
(CH2CH2N), 19.7 (CH3CH2), 13.3 (CH3CH2); m/z (CI+) 414 (10%,
MNH4þ); [HR-MS (ES+): MNH4
,
414.1434. [C18H25N3O6Cl]+
þ
requires 414.1426]; ½a D24
¼ þ31 (c 4, CHCl3).
ꢂ
4.20. (S)-Methyl 1-butyl-3-((S)-2-nitro-1-p-tolylethyl)-2,5-dioxo
pyrrolidine-3-carboxylate 5d and (R)-methyl 1-butyl-3-((S)-2-
nitro-1-p-tolylethyl)-2,5-dioxopyrrolidine-3-carboxylate 6d
Following general method C, the title compounds 5d (71 mg,
58% yield) and 6d (32 mg, 26% yield) were obtained after 48 h as
colourless solids in 91% ee 5d [Chiralpak IB, Hexanes/IPA 85:15,
1.0 mL/min, k 215 nm, t (major) = 14.5 min, t (minor) = 11 min]
and 84% ee 6d [Chiralpak IB, Hexanes/IPA 85:15, 1.0 mL/min, k
215 nm, t (major) = 19.9 min, t (minor) = 16.6 min] as determined
by HPLC analysis.
MS m/z (CI+) 458 (Br78) (40%, MNH4þ) 461 (Br81) (50%, MNH4þ).
[HR-MS (ES+): MNH4
,
458.0910. [C18H21BrN2O6]+ requires
þ
458.0921]; ½a 2D5
ꢂ
¼ þ93:3 (99% ee) (c 0.3, CHCl3).
Data for 6b: Mp 72–74 °C; IR
v
max(film)/cmꢀ1 2958 (CH), 1743
(C@O), 1704 (C@O), 1557; 1H NMR (500 MHz, CDCl3) dH 7.61 (m,
2H, Ar-H), 7.34 (dt, 1H, J = 7.7, 1.3, Ar-H), 7.19 (ddd, 1H, J = 8.0,
7.5, 1.7, Ar-H), 5.59 (dd, 1H, J = 14.1, 3.3, CHAHB-NO2), 5.30 (dd,
1H, J = 14.2, 10.2, CHAHB-NO2), 4.77 (dd, 1H, J = 10.2, 3.4, Ar-⁄CH),
3.81 (s, 3H, CH3O) 3.54 (t, 2H, J = 7.3, CH2N), 2.94 (d, 1H, J = 18.4,
CH2C(O)N), 2.76 (d, 1H, J = 18.4, CH2C(O)N), 1.51 (m, 2H, CH2CH2N)
1.30 (m, 2H, CH3CH2CH2), 0.93 (m, 3H, CH3CH2); 13C NMR
(125 MHz, CDCl3); dC 173.8 (C@O), 173.7 (C@O), 168.5 (C@O),
135.3, 134.0, 130.3, 128.8, 128.7 (Ar-C), 77.0 (CH2NO2), 57.2 (qua-
ternary C), 53.8 (OCH3), 44.5 (CH2N), 39.4 (NO2CH2CH), 37.6
(CH2C(O)N), 29.3 (CH2CH2N), 19.8 (CH3CH2), 13.6 (CH3CH2); MS
m/z (CI+) 458 (Br78) (10%, MNH4þ) 461 (Br81) (20%, MNH4þ). [HR-
Data for 5d: Mp 72–77 °C; IR vmax(film)/cmꢀ1 2959 (CH), 1745
(C@O), 1702 (C@O), 1556; 1H NMR (500 MHz, CDCl3) dH 7.10 (d,
2H, J = 8.0, Ar-H), 7.04 (d, 2H, J = 8.2, Ar-H), 5.26 (m, 1H, CHAHB–
NO2), 5.10 (dd, 1H, J = 13.7, 3.4, CHAHB–NO2), 4.22 (dd, 1H,
J = 10.9, 3.4, Ar-⁄CH), 3.82 (s, 3H, CH3O), 3.45 (t, 2H, J = 7.2,
CH2N), 2.82 (d, 1H, J = 18.3, CH2C(O)N), 2.66 (m, 1H, CH2C(O)N),
2.29 (s, 3H, Ar-CH3), 1.47 (m, 2H, CH2CH2N), 1.23 (m, 2H,
CH3CH2CH2), 0.92 (t, 3H, J = 7.3); 13C NMR (125 MHz, CDCl3) dC
174.7 (C@O), 173.6 (C@O), 169.8 (C@O), 139.2, 130.4, 130.2,
128.8 (Ar-C), 76.9 (CH2NO2), 56.3 (quaternary C), 53.9 (OCH3),
46.2 (CH2N), 39.3 (NO2CH2CH), 38.2 (CH2C(O)N), 29.2 (CH2CH2N),
21.1 (CH3Ar), 19.9 (CH3CH2), 13.6 (CH3CH2); m/z (ES+) 399 (100%,
MNa+); [HR-MS (ES+): MNa+, 399.1530. [C19H24N2O6Na]+ requires
MS (ES+): MNH4 458.0921. [C18H21BrN2O6]+ requires 458.0921];
þ
½
a 2D5
ꢂ
¼ þ68:8 (99% ee) (c 0.5, CHCl3).
399.1527]; ½a 2D1
ꢂ
¼ þ60 (c 0.5, CHCl3).
4.19. (S)-Methyl 1-butyl-3-((R)-1-(2-chlorophenyl)-2-nitroethyl)
-2,5-dioxopyrrolidine-3-carboxylate 5c and (R)-methyl 1-butyl-
3-((R)-1-(2-chlorophenyl)-2-nitroethyl)-2,5-dioxopyrrolidine-
3-carboxylate 6c
Data for 6d: MP: 65–68ꢀC; IR
m
max(film)/cmꢀ1 2959 (CH), 1744
(C@O), 1702 (C@O), 1556 (C@O); 1H NMR (500 MHz, CDCl3) dH
7.11 (s, 4H, Ar-H), 5.09 (dd, 1H, J = 13.3, 4.4, CHAHB-NO2), 4.91
(dd, 1H, J = 13.3, 10.6, CHAHB–NO2), 4.47 (dd, 1 H, J = 10.6, 4.4,
Ar-⁄CH), 3.84 (s, 3H, CH3O), 3.28 (t, 2H, J = 7.0, CH2N), 3.17 (d, 1H,
J = 18.2, CH2C(O)N), 2.82 (d, 1H, J = 18.2, CH2C(O)N), 2.29 (s, 3H,
Ar-CH3), 1.13 (m, 2H, CH2CH2N), 0.98 (m, 2H, CH3CH2CH2), 0.80
(t, 3H, J = 7.3, CH3CH2); 13C NMR (125 MHz, CDCl3) dC 172.8,
172.2, 167.5 (C@O), 138.0, 129.1, 128.9, 127.7 (Ar-C), 74.9
(CH2NO2), 56.6 (quaternary C), 52.9 (OCH3), 44.4 (CH2N), 38.3
(NO2CH2CH), 34.0 (CH2C(O)N), 28.1 (CH2CH2N), 20.0 (CH3Ar), 18.6
Following general method C, the title compounds 5c (90 mg,
69% yield) and 6c (20 mg, 16% yield) were obtained after 48 h as
colourless solids in 96% ee 5c [Chiralpak IB, Hexanes/IPA 85:15,
1.0 mL/min, k 215 nm, t (major) = 13.6 min, t (minor) = 8.4 min]
and 87% ee 6c [Chiralpak IB, Hexanes/IPA 85:15, 1.0 mL/min, k
215 nm, t (major) = 14.6 min, t (minor) = 12.1 min] as determined
by HPLC analysis.
(CH3CH2), 12.5 (CH3CH2); m/z (ES+) 394 (100%, MNH4þ); [HR-MS
Data for 5c: Mp 84–87 °C; IR v
max(film)/cmꢀ1 2959 (CH), 1746
þ
(ES+): MNH4
,
394.1982. [C19H28N3O6]+ requires 394.1973];
(C@O), 1703 (C@O), 1556; 1H NMR (500 MHz, CDCl3) dH 7.45 (dd,
1H, J = 8.0, 1.1, Ar-H), 7.27 (m, 1H, Ar-H), 7.20 (m, 2H, Ar-H), 5.33
(dd, 1H, J = 14.2, 11.0, CHAHB–NO2), 5.20 (dd, 1H, J = 14.2, 3.4,
CHAHB–NO2), 5.11 (dd, 1H, J = 10.9, 3.4, Ar-⁄CH), 3.85 (s, 3H,
CH3O), 3.46 (m, 2H, CH2N), 2.88 (d, 1H, J = 18.6, CH2C(O)N) 2.64
(d, 1H, J = 18.6, CH2C(O)N) 1.49 (m, 2H, CH2CH2N) 1.22 (m, 2H,
CH3CH2CH2) 0.91 (t, 3H, J = 7.3, CH3CH2); 13C NMR (125 MHz,
CDCl3) 174.6 (C@O), 173.5 (C@O), 169.5 (C@O), 136.2, 131.9,
130.9, 130.3, 127.9, 127.7 (Ar-C), 76.2 (CH2NO2), 56.3 (quaternary
C), 54.0 (OCH3), 40.7 (CH2N), 39.3 (NO2CH2CH), 37.5 (CH2C(O)N),
29.3 (CH2CH2N), 19.9 (CH3CH2), 13.5 (CH3CH2); MS m/z (CI+) 414
(20%, MNH4þ). [HR-MS (ES+): MNH4þ, 414.1433. [C18H25N3O6Cl]+
½
a 2D1
ꢂ
¼ ꢀ32:4 (c 0.5, CHCl3).
4.21. (S)-Methyl 1-butyl-3-((S)-1-(3-methoxyphenyl)-2-nitroeth
yl)-2,5-dioxopyrrolidine-3-carboxylate 5e and (R)-methyl 1-bu
tyl-3-((S)-1-(3-methoxyphenyl)-2-nitroethyl)-2,5-dioxopyrroli
dine-3-carboxylate 6e
Following general method C, the title compounds 5e (74 mg,
57% yield) and 6e (21 mg, 16% yield) were obtained after 48 h as
colourless oils in 96% ee 5e [Chiralpak IB, Hexanes/IPA 85:15,
1.0 mL/min, k 215 nm, t (major) = 17.5 min, t (minor) = 15.3 min]
and 91% ee 6e [Chiralpak IB, Hexanes/IPA 85:15, 1.0 mL/min, k
215 nm, t (major) = 29.4 min, t (minor) = 22.1 min] as determined
by HPLC analysis.
requires 414.1426]; ½a D24
¼ þ49 (c 1, CHCl3).
ꢂ
Data for 6c: Mp 74–76 °C;
v
max(film)/cmꢀ1 2958, 2874 (CH),
1800, 1751, 1715 (C@O); 1H NMR (500 MHz, CDCl3) dH ppm 7.43
(dd, 1H, J = 8.0, 1.1, Ar-H)) 7.25 (m, 1H, Ar-H)) 7.19 (m, 2H, Ar-
H)) 5.31 (dd, 1H, J = 14.2, 11.0, CHAHB-NO2) 5.18 (dd, 1H, J = 14.2,
Data for 5e: IR
v
max(film)/cmꢀ1 2959 (CH), 1745 (C@O), 1702
(C@O), 1556 (C@O); 1H NMR (500 MHz, CDCl3) dH 7.15 (m, 1H,

1154
P. Jakubec et al. / Tetrahedron: Asymmetry 22 (2011) 1147–1155
Ar-H), 6.76 (m, 1H, Ar-H), 6.67 (m, 1H, Ar-H), 6.62 (m, 1H, Ar-H),
5.20 (dd, 1H, J = 13.9, 10.8, CHAHB-NO2), 5.04 (dd, 1H, J = 13.9, 3.4,
CHAHB-NO2), 4.16 (dd, 1H, J = 10.8, 3.4, Ar-⁄CH), 3.76 (s, 3H,
CH3O), 3.69 (s, 3H, ArOCH3), 3.39 (t, 2H, J = 7.4, CH2N), 2.75 (d,
1H, J = 18.3, CH2C(O)N), 2.62 (d, 1H, J = 18.3, CH2C(O)N), 1.40 (m,
2H, CH2CH2N), 1.16 (m, 2H, CH3CH2CH2), 0.85 (t, 3H, J = 7.4,
CH3CH2); 13C NMR (125 MHz, CDCl3) dC 174.5 (C@O), 173.4
(C@O), 169.6 (C@O), 159.9, 135.0, 130.4, 120.8, 115.3, 113.7 (Ar-
C), 76.8 (CH2NO2), 56.0 (quaternary C), 55.0 (ArOCH3), 53.7
(OCH3), 46.3 (CH2N), 39.2 (NO2CH2CH), 38.0 (CH2C(O)N), 29.1
(CH2CH2N), 19.7 (CH3CH2), 13.4 (CH3CH2); m/z (CI+) 410 (30%,
MNH4þ); [HR-MS (ES+): MNH4þ, 410.1914, [C19H28N3O7]+ requires
MNH4þ, 370.1602. [C16H24N3O7]+ requires 370.1609]; ½a D24
¼ ꢀ42
ꢂ
(c 1, CHCl3).
4.23. (S)-Methyl 1-butyl-3-((S)-1-(naphthalen-2-yl)-2-
nitroethyl)-2,5-dioxopyrrolidine-3-carboxylate 5g and (R)-
methyl 1-butyl-3-((S)-1-(naphthalen-2-yl)-2-nitroethyl)-2,5-
dioxopyrrolidine-3-carboxylate 6g
Following general method C, the title compounds 5g (87 mg,
64% yield) and 6g (43 mg, 32% yield) were obtained after 48 h as
colourless solids in 95% ee 5g [Chiralpak IB, Hexanes/IPA 85:15,
1.0 mL/min, k 215 nm, t (major) = 16.3 min, t (minor) = 24 min]
and 90% ee 6g [Chiralpak IB, Hexanes/IPA 85:15, 1.0 mL/min, k
215 nm, t (major) = 25.1 min, t (minor) = 52 min] as determined
by HPLC analysis.
410.1922]; ½a 2D4
¼ þ48 (c 1, CHCl3).
ꢂ
Data for 6e: IR vmax(film)/cmꢀ1 2959 (CH), 1747 (C@O), 1702
(C@O), 1555 (C@O); 1H NMR (500 MHz, CDCl3) dH 7.22 (t, 1H,
J = 8.0 Hz,, Ar-H), 6.80 (m, 3H, Ar-H), 5.12 (dd, 1H, J = 13.5, 4.3,
CHAHB-NO2), 4.93 (dd, 1H, J = 13.5, 10.5, CHAHB–NO2), 4.46 (dd,
1H, J = 10.5, 4.3, Ar-⁄CH), 3.84 (s, 3H, CH3O), 3.77 (s, 3H, ArOCH3),
3.30 (t, 2H, J = 7.1, CH2N), 3.17 (d, 1H, J = 18.2, CH2C(O)N), 2.82
(d, 1H, J = 18.2, CH2C(O)N), 1.30 (m, 2H, CH2CH2N), 1.03 (m, 2H
CH3CH2CH2), 0.81 (t, 3H, J = 7.3); 13C NMR (125 MHz, CDCl3) dC
173.7 (C@O), 173.2 (C@O), 168.4 (C@O), 160.0, 134.8, 130.3,
120.4, 115.3, 114.2 (Ar-C), 75.8 (CH2NO2), 57.6 (quaternary C),
55.2 (ArOCH3), 54.0 (OCH3), 45.7 (CH2N), 39.3 (NO2CH2CH), 35.2
Data for 5g: Mp 94–97 °C; IR m
max(film)/cmꢀ1 2959 (CH), 1745
(C@O), 1703 (C@O), 1556 (C@O); 1H NMR (500 MHz, CDCl3) dH
7.78 (m, 3H, Ar-H), 7.66 (d, 1H, J = 1.6, Ar-H), 7.50 (m, 2H, Ar-H),
7.25 (dd, 1H, J = 8.5, 1.9, Ar-H), 5.43 (dd, 1H, J = 13.9, 10.9,
CHAHB–NO2), 5.21 (dd, 1H, J = 13.9, 3.4, CHAHB-NO2), 4.45 (dd, 1H,
J = 10.9, 3.3, Ar-⁄CH), 3.83 (m, 3H, CH3O), 3.45 (dt, 2H, J = 8.0, 6.9,
2.8, CH2N), 2.86 (d, 1H, J = 18.3, CH2C(O)N), 2.72 (d, 1H, J = 18.3,
CH2C(O)N), 1.52 (m, 2H, CH2CH2N), 1.39 (m, 2H, CH2CH2N), 1.20
(m, 2H, CH3CH2CH2), 0.88 (t, 3H, J = 7.4, CH3CH2); 13C NMR
(125 MHz, CDCl3) dC 174.6 (C@O), 173.2 (C@O), 169.6 (C@O),
133.1, 133.0, 130.8, 129.4, 128.7, 127.7, 127.6, 126.8, 126.8, 125.5
(Ar-C), 76.7 (CH2NO2), 56.2 (quaternary C), 53.8 (OCH3), 46.5
(CH2N), 39.2 (NO2CH2CH), 38.0 (CH2C(O)N), 29.1 (CH2CH2N), 19.7
(CH2C(O)N), 29.1 (CH2CH2N), 19.6 (CH3CH2), 13.5 (CH3CH2); m/z
þ
(CI+) 410 (40%, MNH4þ); [HR-MS (ES+): MNH4
, 410.1923.
[C19H24N2O7]+ requires 410.1922]; ½a 2D4
¼ ꢀ35 (c 0.7, CHCl3).
ꢂ
4.22. (S)-Methyl 1-butyl-3-((S)-1-(furan-2-yl)-2-nitroethyl)-2,5-
dioxopyrrolidine-3-carboxylate 5f and (R)-methyl 1-butyl-3-
((S)-1-(furan-2-yl)-2-nitroethyl)-2,5-dioxopyrrolidine-3-car
boxylate 6f
(CH3CH2), 13.4 (CH3CH2); m/z (CI+) 430 (20%, MNH4þ); [HR-MS
(ES+): MNH4
,
430.1966. [C22H28N3O6]+ requires 430.1967];
þ
½
a 2D3
ꢂ
¼ þ2:0 (c 0.4, CHCl3).
Data for 6g: Mp 121–124 °C; IR
v
max(film)/cmꢀ1 2958 (CH),
1743 (C@O), 1705 (C@O), 1557 (C@O); 1H NMR (500 MHz, CDCl3)
dH 7.81 (m, 3H, Ar-H), 7.71 (d, 1H, J = 1.6, Ar-H), 7.50 (m, 2H, Ar-
H), 7.34 (dd, 1H, J = 8.6, 1.9, Ar-H), 5.22 (dd, 1H, J = 13.4, 4.3,
CHAHB–NO2), 5.08 (dd, 1H, J = 13.4, 10.5, CHAHB–NO2), 4.67 (dd,
1H, J = 10.5, 4.3, Ar-⁄CH), 3.87 (s, 3H, CH3O), 3.23 (m, 3H, CH2C(O)N,
CH2N), 2.93 (d, 1H, J = 18.2, CH2C(O)N), 0.94 (m, 2H, CH2CH2N), 0.80
(m, 2H, CH3CH2CH2), 0.54 (t, 3H, J = 7.2, CH3CH2); 13C NMR
(125 MHz, CDCl3) dC 173.5 (C@O), 173.0 (C@O), 168.3 (C@O),
133.0, 132.9, 130.5, 129.1, 128.7, 127.9, 127.4, 126.8, 126.7, 125.4
(Ar-C), 75.7 (CH2NO2), 57.5 (quaternary C), 53.9 (OCH3), 45.7
(CH2N), 39.1 (NO2CH2CH), 35.1 (CH2C(O)N), 28.8 (CH2CH2N), 19.3
Following general method C, the title compounds 5f (63 mg,
54% yield) 6f (42 mg, 36% yield) were obtained after 48 h as colour-
less oils in 94% ee 5f [Chiralpak IB, Hexanes/IPA 85:15, 1.0 mL/min,
k 215 nm, t (major) = 16.8 min, t (minor) = 10.5 min] and 91% ee 6f
[Chiralpak IB, Hexanes/IPA 85:15, 1.0 mL/min, k 215 nm, t (ma-
jor) = 16.5 min,
analysis.
t
(minor) = 13.9 min] as determined by HPLC
Data for 5f: IR
m
max(film)/cmꢀ1 2959 (CH); 1745 (C@O), 1707
(C@O); 1557 (C@O); m/z (ES+) 370 (30%, MNH4þ); 1H NMR
(500 MHz, CDCl3) dH ppm 7.31 (m, 1H, Ar-H) 6.33 (m, 2H, Ar-H),
5.14 (dd, 1H, J = 13.8, 10.6, CHAHB-NO2), 5.03 (dd, 1H, J = 13.8, 3.3,
CHAHB–NO2), 4.50 (dd, 1H, J = 10.6, 3.2, Het-⁄CH), 3.84 (s, 3H,
CH3O), 3.51 (t, 2H, J = 7.4, CH2N), 2.93 (d, 1H, J = 18.3, CH2C(O)N),
2.75 (d, 1H, J = 18.4, CH2C(O)N), 1.53 (m, 2H, CH2CH2N), 1.31 (m,
2H, CH3CH2CH2), 0.95 (t, 3H, J = 7.3, CH3CH2); 13C NMR (125 MHz,
CDCl3) dC 173.9 (C@O), 173.5 (C@O), 169.2 (C@O), 147.7, 143.6,
111.3, 110.9 (Het-C), 75.1 (CH2NO2), 55.5 (quaternary C), 54.0
(OCH3), 40.6 (NO2CH2CH), 39.4 (CH2C(O)N), 38.3 (CH2N), 29.2
(CH2CH2N), 19.9 (CH3CH2), 13.6 (CH3CH2); MS m/z (ES+) 375
(100%, MNa+); [HR-MS (ES+): 370.1609, C16H24N3O7 requires
(CH3CH2), 13.1 (CH3CH2); m/z (ES+) 430 (30%, MNH4þ); [HR-MS
þ
(ES+): MNH4
,
430.1977. [C22H28N3O6]+ requires 430.1967];
[a]D = +30.0 (c 0.2, CHCl3).
Acknowledgements
We gratefully acknowledge the EPSRC for a postdoctoral fellow-
ship (to P.J.) and Leadership Fellowship (to D.J.D.), Pfizer Global Re-
search and Development for a studentship (to P.S.H.), Merck, Sharp
and Dohme (Hoddesdon, UK) for a CASE award (to D.M.C.), The
University of Manchester for a studentship (to D.M.C.) and Dr. M.
Helliwell for single crystal X-ray diffraction analysis. D.J.D. would
like to thank Saidul Islam, Kirsty Midwood, Collette Turner and
James Whittaker for preliminary studies.
370.1609]; ½a 2D5
ꢂ
¼ þ27:6 (c 3.7, CHCl3).
Data for 6f: IR
m
max(film)/cmꢀ1 2959 (CH), 1745 (C@O), 1709
(C@O), 1559 (C@O); 1H NMR (500 MHz, CDCl3) dH 7.32 (s, 1H, Ar-
H), 6.29 (d, 2H, J = 1.3, Ar-H), 4.93 (dd, 1H, J = 13.2, 4.3, CHAHB–
NO2), 4.86 (dd, 1H, J = 13.1, 9.9, CHAHB-NO2), 4.71 (dd, 1H, J = 9.9,
4.3, Het-⁄CH), 3.83 (s, 3H, CH3O), 3.36 (dt, 2H, J = 7.5, 1.6, CH2N),
3.19 (d, 1H, J = 18.1, CH2C(O)N), 3.01 (d, 1H, J = 18.1, CH2C(O)N),
1.29 (m, 2H, CH2CH2N), 1.13 (m, 2H, CH3CH2CH2), 0.84 (t, 3H,
J = 7.3, CH3CH2); 13C NMR (125 MHz, CDCl3) dC 173.7 (C@O), 172.7
(C@O), 167.8 (C@O), 147.2, 143.3, 110.9, 110.6 (Het-C), 74.1
(CH2NO2), 57.0 (Het-C), 53.8 (OCH3), 39.5 (NO2CH2CH), 39.1
(CH2C(O)N), 35.0 (CH2N), 29.0 (CH2CH2N), 19.5 (CH3CH2),
13.2 (CH3CH2); m/z (ES+) 370 (40%, MNH4þ); [HR-MS (ES+):
References
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P. Jakubec et al. / Tetrahedron: Asymmetry 22 (2011) 1147–1155
1155
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