Metal-free asymmetric 1,3-dipolar cycloaddition of N-arylmaleimides to azomethine ylides catalyzed by chiral tertiary amine thiourea

Article abstract of DOI:10.1002/ejoc.201100205

The first metal-free asymmetric 1,3-dipolar cycloaddition of N-arylmaleimides to azomethine ylides catalyzed by chiral tertiary amine thiourea to form multiply substituted pyrrolidines in excellent yields (up to 89%) and enantioselectivities (up to 96% ee) is presented. This procedure allows a rapid diversity-oriented synthesis of chiral pyrrolidine derivatives with high optical purity. A series of bifunctional thiourea catalysts were applied for the first time to the highly asymmetric 1,3-dipolar cycloaddition of N-arylmaleimides to azomethine ylides togive the products in excellent yields (up to 89%) and enantioselectivities (up to 96% ee).

Full text of DOI:10.1002/ejoc.201100205

FULL PAPER
DOI: 10.1002/ejoc.201100205
Metal-Free Asymmetric 1,3-Dipolar Cycloaddition of N-Arylmaleimides to
Azomethine Ylides Catalyzed by Chiral Tertiary Amine Thiourea
Jian-Fei Bai,[a,b] Liang-Liang Wang,[a,b] Lin Peng,[a,b] Yun-Long Guo,[a,b] Jun-Nan Ming,[a]
Fei-Ying Wang,[a] Xiao-Ying Xu,*[a] and Li-Xin Wang*[a]
Keywords: Cycloaddition / Organocatalysis / Diastereoselectivity / Enantioselectivity / Azomethine ylides
The first metal-free asymmetric 1,3-dipolar cycloaddition of
N-arylmaleimides to azomethine ylides catalyzed by chiral
tertiary amine thiourea to form multiply substituted pyrrol-
idines in excellent yields (up to 89%) and enantioselectivities
(up to 96% ee) is presented. This procedure allows a rapid
diversity-oriented synthesis of chiral pyrrolidine derivatives
with high optical purity.
troalkenes catalyzed by a bifunctional tertiary amine-
urea.[10e] Despite intense efforts, an organocatalytic asym-
metric version of 1,3-dipolar cycloaddition of azomethine
ylides has remained elusive. To date, there has been no re-
port of organocatalytic asymmetric 1,3-dipolar cycload-
dition of azomethine to maleimides, which could afford bio-
logical or clinical heterocycles with important and easily
transformable succinimide motifs.[11] It is still desirable and
challenging to develop new catalytic systems that bring
about this useful transformation.
Recently, bifunctional thiourea catalysts have been inves-
tigated extensively in organocatalysis as a particular tool to
activate both donors and acceptors simultaneously.[12] In
our previous work, thiourea was shown to activate maleim-
ides effectively through hydrogen bonds.[13a] Inspired by this
concept, we recognized that the tertiary amine group would
activate the α-imino esters as bases to produce azomethine
ylides,[10e] whereas the thiourea group would activate N-ar-
ylmaleimides through double hydrogen bonds. Thus, the
synergistic interactions through chiral tertiary amine thio-
urea bifunctional catalysis would ensure high stereoselecti-
vities in the subsequent dipolar cycloaddition, affording the
corresponding optically active products through a pos-
tulated transition state (TS) shown in Figure 1. As a part
of our continuing interests in asymmetric syntheses,[13]
herein, we wish to report the first organocatalytic asymmet-
Introduction
Optically active five-membered nitrogen heterocycles are
important motifs in natural alkaloids, pharmaceutically
active substances, and key intermediates in total synthe-
ses.[1] The significance of these structures has inspired
chemists to develop new asymmetric strategies to access
these interesting five-membered heterocycles.[2] Among
them, the catalytic asymmetric 1,3-dipolar cycloaddition of
activated alkenes to azomethine ylides is a straightforward
way to construct functionalized pyrrolidines.[3] Over the
past years, a variety of chiral metal catalysts including cop-
per,[4] silver,[5] nickel,[6] zinc,[7] calcium,[8] and gold[9] have
been successfully developed, which are generally used in
combination with chiral ligands to afford moderate to high
enantio-/diastereoselectivities. However, the development of
more efficient and environmentally friendly methodologies
in asymmetric catalysis, especially metal-free small molecu-
lar catalysis, is still a challenge.[10] In 2007, Vicario and co-
workers reported the organocatalytic enantioselective cyclo-
addition of azomethine ylides to α,β-unsaturated aldehydes
in good enantioselectivities.[10a] Subsequently, Gong and co-
workers reported a Brønsted acid catalyzed three-compo-
nent 1,3-dipolar cycloaddition between aldehydes, amino
esters, and dipolarophiles.[10c] Additionally, nitroalkenes
were also evaluated in this conversion.[10g] In the same year,
Chen reported the organocatalytic, one-pot, three-compo-
nent reaction of aldehydes, diethyl aminomalonate, and ni-
[a] Key Laboratory of Asymmetric Synthesis and Chirotechnology
of Sichuan Province, Chengdu Institute of Organic Chemistry,
Chinese Academy of Sciences,
Chengdu 610041, P. R. of China
Fax: +86-028-8525-5208
E-mail: wlxioc@cioc.ac.cn
xuxy@cioc.ac.cn
[b] Graduate University of Chinese Academy of Sciences,
Beijing 10039, P. R. of China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100205.
Figure 1. Proposed transition state.
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4472–4478

Cycloaddition of N-Arylmaleimides to Azomethine Ylides
ric 1,3-dipolar cycloaddition of N-arylmaleimides and azo-
methine ylides promoted by chiral tertiary amine thiourea
catalysts, yielding multiply substituted pyrrolidines in excel-
lent enantioselectivities (up to 96% ee). This procedure al-
lows a rapid diversity-oriented synthesis of chiral pyrroli-
dine derivatives.
Results and Discussion
Based on the above hypothesis, a series of catalysts with
various substituents 1a–g (Figure 2) were synthesized and
evaluated.[14] We chose N-benzylideneglycine methyl ester
(2a) and N-phenylmaleimide (3a) as the model reaction
substrates to screen a range of chiral tertiary amine thio-
ureas and found that the adduct endo-4a was obtained with
highly variable yield as shown in Table 1.[15] For catalysts
1a and 1b, only moderate yields and low enantioselectivities
were obtained (Table 1, entries 1 and 2). Catalyst 1a, with
cyclohexanediamine as a chiral scaffold, afforded better
yield and enantioselectivity (61% yield, 63% ee) than cata-
lyst 1b, with a diphenyldiamine scaffold (21% yield, 7% ee;
Table 1, entry 1 vs. 2). Catalysts 1c–f, with cyclic substitu-
tion on the nitrogen atom, afforded better enantioselectivit-
ies (up to 91% ee; Table 1, entries 3–6) than those with
methyl substitutions (Table 1, entries 1 and 2). More acidic
N–H thiourea groups seem to have a detrimental effect on
the catalytic activity. Catalysts 1c and 1e, with no substitu-
tions on the phenyl ring, gave better enantioselectivities
than those with 3,5-bis(trifluoromethyl) groups (Table 1,
entries 3 vs. 5, and 4 vs. 6). Catalysts 1e and 1f afforded
good enantioselectivities but poor yields (Table 1, entries 5
and 6). When the commonly used cinchona alkaloid based
thioureas 1g and 1h were evaluated, almost racemic adducts
were obtained (Table 1, entries 7 and 8). Catalyst 1c thus
gave the best enantioselectivity with an acceptable yield,
and was selected for further optimization.
Figure 2. Organocatalysts assessed in this study.
Table 1. 1,3-Dipolar cycloaddition reaction of 2a and 3a.[a]
Other reaction conditions, such as substrate loadings,
solvents, and additives, were then screened (Table 2). Ex-
cessive loading of azomethine ylides (2a) is unfavorable and
the enantioselectivities decreased gradually with increasing
ylide loadings (Table 2, entries 1–3). In contrast, use of an
excess amount of N-phenylmaleimide (3a) gave better
yields, while the enantioselectivities remained almost un-
changed (Table 2, entries 1, 4, and 5). A molecular ratio of
1:1.5 reactants 2a and 3a gave the highest enantioselectivity
(91% ee; Table 2, entry 4) and was chosen for further opti-
mization. Solvents were also found to have remarkable ef-
fects on the enantioselectivities (Table 2, entries 6–13);
CH2Cl2 gave the highest ee (93%) with moderate yield
(64%, Table 1, entry 4) and was chosen as the most suitable
solvent. It was reported in the literature[10e] that addition of
molecular sieves (4 Å) can have a positive effect on the reac-
tion yield of similar transformations. We also observed that
Entry
Cat.
Yield [%][b]
ee [%][c,d]
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
61
21
50
68
19
26
82
83
63
7
91
76
82
73
7
1g
1h
1
[a] Reagents and conditions: 2a (0.20 mmol), 3a (0.20 mmol), anhy-
drous CH2Cl2 (0.8 mL), –20 °C, 60 h. [b] Isolated yield of the endo
isomer. [c] Enantiomeric excesses were determined by chiral HPLC
analysis. [d] The absolute configuration of the known compound
4a was determined by optical rotation comparisons with reported
data.[4i]
when molecular sieves (4 Å) was added, the yield increased reaction time. The highest yield was obtained when the re-
remarkably and the enantioselectivity was not decreased action was undertaken in the presence of 25 mol-% 1c for
(69% yield, 93% ee; Table 2, entry 14). Generally, the yields 72 h (85% yield; Table 2, entry 16). Based on the above re-
were clearly affected by both the catalyst loading and the sults, optimal reaction conditions (1.0 equiv. 2a and
Eur. J. Org. Chem. 2011, 4472–4478
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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X.-Y. Xu, L.-X. Wang et al.
FULL PAPER
1.5 equiv. 3a in CH2Cl2 with 25 mol-% catalyst 1c and 4 Å Table 3. Scope of azomethine ylides.[a]
molecular sieves at –20 °C) were established.
Table 2. Optimization of the reaction conditions.[a]
Entry
R
2
4
Yield [%][b] ee [%][c]
1
2
3
4
5
6
7
8
Ph
2a
2b
2c
2d
2e
2f
2g
2h
2i
2i
2k
2l
2m
2n
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
85
77
89
84
79
72
72
85
64
75
71
51
86
82
93
67
90
95
96
90
86
90
85
93
87
70
90
91
4-NO2C6H4
4-BrC6H4
4-ClC6H4
4-CH3OC6H4
4-CH3C6H4
3-ClC6H4
3-BrC6H4
3-NO2C6H4
3-CH3C6H4
2-CH3OC6H4
2-NO2C6H4
1-naphthyl
2-furyl
Entry 2a/3a ratio
Solvent
Yield [%][b] ee [%][c,d]
1
2
3
4
5
6
7
8
1:1
2:1
5:1
1:1.5
1:2
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
ClCH2CH2Cl 63
Et2O
toluene
xylene
THF
50
62
58
64
61
65
91
87
80
93
91
78
89
80
80
83
73
67
89
93
95
93
9
10
11
12
13
14
55
62
65
52
33
60
69
79
85
[a] Reagents and conditions: 2 (0.30 mmol), 3a (0.45 mmol), MS
(4 Å, 300 mg), anhydrous CH2Cl2 (1.0 mL), –20 °C, 72 h. [b] Iso-
lated yield. [c] Enantiomeric excesses were determined by chiral
HPLC analysis.
9
10
11
12
13
14[e]
DMF
CH3CN
CH2Cl2
CH2Cl2
CH2Cl2
Table 4. Scope of N-arylmaleimides.[a]
15[e,f] 1:1.5
16[e,f,g] 1:1.5
[a] Reagents and conditions: 2a (0.20 mmol), 3a (0.20 mmol), anhy-
drous solvent (0.8 mL), –20 °C, 60 h. [b] Isolated yield of the endo
isomer. [c] Enantiomeric excesses were determined by chiral HPLC
analysis. [d] The absolute configuration of the known compound
4a was determined by comparison of the optical rotation with re-
ported data.[4i] [e] MS (4 Å, 300 mg) was added. [f] 1c (25 mol-%)
was added. [g] The reaction time was 72 h.
Under the optimal conditions, the scope of the reaction
was investigated; the substituents of azomethine ylides 2
and N-arylmaleimides 3 are listed in Table 3 and Table 4.
All the reactions proceeded smoothly and all the substrates
gave moderate to good yields (up to 89%) and satisfactory
enantioselectivities (up to 96% ee). The electronic nature
and position of the substituents on the azomethine ylides
phenyl ring had some influence on the enantioselectivities.
Strong electron-withdrawing groups on the phenyl ring of
2 decreased the yields and enantioselectivities remarkably
(Table 3, entries 2, 9, and 12), whereas electron-rich groups
on the phenyl ring of 2 gave the highest enantioselectivity
(96% ee; Table 3, entry 5). 1-Naphthyl and 2-furyl azo-
methine ylides also worked well (Table 3, entries 13 and 14)
and gave good results. The electronic property and position
of the substituents on the arylmaleimides phenyl ring affec-
ted the enantioselectivities slightly. All reactions gave high
yields and excellent enantioselectivities (up to 87% yield
Entry
R
3
5
Yield [%][b] ee [%][c]
1
2
3
4
5
6
7
8
Ph
3a
3b
3c
3d
5a
5b
5c
5d
5e
5f
5g
5h
5i
85
84
81
70
74
85
87
73
82
66
75
93
87
92
73
95
90
85
90
82
88
30
4-FC6H4
4-ClC6H4
4-NO2C6H4
4-CH3OC6H4 3e
4-CH3C6H4
3-FC6H4
2-FC6H4
2-CH3C6H4
1-naphthyl
CH3
3f
3g
3h
3i
3j
3k
9
10
11
5j
5k
[a] Reagents and conditions: 2a (0.30 mmol), 3 (0.45 mmol), MS
(4 Å, 300 mg), CH2Cl2 (1.0 mL), –20 °C, 72 h. [b] Isolated yield. [c]
Enantiomeric excesses were determined by chiral HPLC analysis.
Conclusions
We have developed a highly enantioselective formal 1,3-
and 95% ee; Table 4), except with N-1-naphthyl maleimide dipolar cycloaddition reaction between azomethine ylides
3j, which gave lower yield (66%) and enantioselectivity and N-arylmaleimides catalyzed by chiral tertiary amine
(88% ee; Table 4, entry 10). Disappointedly, the aliphatic thiourea. This protocol has provided a new approach to the
N-substituted maleimide 3k gave poor enantioselectivity preparation of functionalized pyrolidines in excellent yields
(30% ee; Table 4, entry 11).
(up to 89%) and enantioselectivities (up to 96% ee), and
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Eur. J. Org. Chem. 2011, 4472–4478

Cycloaddition of N-Arylmaleimides to Azomethine Ylides
(1R,3S,3aR,6aS)-Methyl 4,6-Dioxo-3,5-diphenyloctahydropyrrolo-
[3,4-c]pyrrole-1-carboxylate (4a): This is a known compound.[4i]
The product was obtained according to the general procedure as
described above in 85% yield as a white solid. [α]2D0 = –93.4(c = 1.1,
CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 7.47–7.41 (m, 2 H),
7.30–7.28 (m, 6 H), 7.14 (d, J = 7.4 Hz, 2 H), 4.63 (d, J = 8.75 Hz,
1 H), 4.16 (d, J = 6.63 Hz, 1 H), 3.87 (s, 3 H), 3.73 (t, J = 7.6 Hz,
1 H), 3.57 (t, J = 8.7 Hz, 1 H), 2.39 (br. s, 1 H, NH) ppm. 13C
NMR (CDCl3, 75 MHz): δ = 175.0, 173.6, 170.0, 136.6, 131.6,
128.9, 128.6, 128.5, 127.0, 126.1, 64.2, 61.8, 52.3, 49.4, 48.3 ppm.
HRMS (ESI): calcd. for C20H18N2NaO4 [M + Na] 373.1159; found
373.1153. Enantiomeric excess: 93%, determined by HPLC (Chi-
ralpak AS-H column; hexane/2-propanol = 50:50; 0.6 mL/min;
230 nm), tR (minor) = 15.5 min, tR (major) = 25.5 min.
holds great potential in the environmentally friendly synthe-
sis of highly substituted five-membered nitrogen heterocy-
cles.
Experimental Section
General Methods: All regents were obtained from commercial sup-
pliers and used without further purification. Commercial grade sol-
vent was dried and purified by standard procedures as specified in
Purification of Laboratory Chemicals, 4th Ed (Armarego, W. L. F.
Perrin, D. D. Butterworth Heinemann, 1997). NMR spectra were
recorded with tetramethylsilane as the internal standard. 1H NMR
spectra were recorded at 300 MHz, and 13C NMR spectra were
recorded at 75 MHz (Bruker Avance). Chemical shifts (δ) are re-
ported in ppm downfield from CDCl3 (δ = 7.26 ppm) for 1H NMR
(1R,3S,3aR,6aS)-Methyl 3-(4-Nitrophenyl)-4,6-dioxo-5-phenylocta-
hydropyrrolo[3,4-c]pyrrole-1-carboxylate (4b): This is a known com-
pound.[4i] The product was obtained according to the general pro-
and relative to the central CDCl3 resonance (δ = 77.0 ppm) for 13
C
cedure as described above in 77% yield as a white solid. [α]2D0
=
NMR spectroscopy. Flash column chromatography was carried out
using silica gel eluting with ethyl acetate and petroleum ether. Reac-
tions were monitored by TLC and visualized with ultraviolet light.
Enantiomeric excess was determined by HPLC analysis on Chi-
ralpak AS-H column. The absolute configurations of the known
products were assigned by HPLC and by comparison of the optical
rotation with the reported data;[4i] those of other adducts were de-
duced on the basis of those results.
–118.9 (c = 1.1, CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 8.20 (d,
J = 8.67 Hz, 2 H), 7.64 (d, J = 8.64 Hz, 2 H), 7.42–7.28 (m, 3 H),
7.11 (d, J = 7.29 Hz, 2 H), 4.69 (d, J = 8.49 Hz, 1 H), 4.19 (d, J =
6.78 Hz, 1 H), 3.88 (s, 3 H), 3.77 (t, J = 7.56 Hz, 1 H), 3.64 (t, J =
8.25 Hz, 1 H), 2.04 (br. s, 1 H, NH) ppm. Enantiomeric excess:
67%, determined by HPLC (Chiralpak AS-H column; hexane/2-
propanol = 50:50; 0.6 mL/min; 230 nm), tR (minor) = 37.5 min, tR
(major) = 61.1 min.
General Procedure for the Synthesis of α-Imino Esters: Et3N (3.6 g,
36 mmol) was added to a suspension of the corresponding amino
acid ester hydrochloride (36 mmol) and MgSO4 (60 mmol) in
CH2Cl2 (30 mL). The mixture was stirred at room temperature for
1 h, then the corresponding aldehyde (30 mmol) was added. The
reaction was stirred at room temperature overnight, then the re-
sulting precipitate was removed by filtration. The filtrate was
washed twice with water (30 mL), the aqueous phase was extracted
once with CH2Cl2 (30 mL) and the combined organic phase was
washed with brine three times, dried with Na2SO4, and concen-
trated. The resulting imino esters were used in 1,3-dipolar cycload-
dition reactions without further purification.
(1R,3S,3aR,6aS)-Methyl
3-(4-Bromophenyl)-4,6-dioxo-5-phenyl-
octahydropyrrolo[3,4-c]pyrrole-1-carboxylate (4c): This is a known
compound.[4i] The product was obtained according to the general
procedure as described above in 89% yield as a white solid. [α]2D0
=
1
–131.6 (c = 1.5, CHCl3). H NMR (CDCl3, 300 MHz): δ = 7.49–
7.46 (m, 2 H), 7.42–7.35 (m, 5 H), 7.13 (d, J = 7.12 Hz, 2 H), 4.55
(d, J = 8.65 Hz, 1 H), 4.13 (d, J = 6.70 Hz, 1 H), 3.87 (s, 3 H),
3.73 (t, J = 6.98 Hz, 1 H), 3.55 (t, J = 8.1 Hz, 1 H), 2.04 (br. s,
1 H, NH) ppm. Enantiomeric excess: 90%, determined by HPLC
(Chiralpak AS-H column; hexane/2-propanol = 50:50; 0.6 mL/min;
230 nm), tR (minor) = 22.4 min, tR (major) = 48.7 min.
(1R,3S,3aR,6aS)-Methyl 3-(4-Chlorophenyl)-4,6-dioxo-5-phenyloc-
tahydropyrrolo[3,4-c]pyrrole-1-carboxylate (4d): This is a known
compound.[4i] The product was obtained according to the general
Preparation of Catalysts: The catalysts 1a–h were prepared accord-
ing to literature methods.[14,16]
procedure as described above in 84% yield as a white solid. [α]2D0
=
1-Phenyl-3-[(1S,2S)-2-(pyrrolidin-1-yl)cyclohexyl]thiourea (1c): Iso-
thiocyanatobenzene (0.8 g, 6.0 mmol, 1.0 equiv.) was added to a
solution of (1S,2S)-2-(pyrrolidin-1-yl)cyclohexanamine (1.0 g,
6.0 mmol, 1.0 equiv.) in CH2Cl2 (10 mL) at room temperature. The
resulting solution was stirred overnight, then concentrated in vacuo
and purified by chromatography (PE/EtOAc/NEt3, 5:1 to 1:1) to
afford 1-phenyl-3-[(1S,2S)-2-(pyrrolidin-1-yl)cyclohexyl]thiourea
(1c; 1.55 g, 85% yield) as a yellow solid. 1H NMR (300 MHz,
CDCl3): δ = 7.35 (t, J = 7.38 Hz, 2 H), 7.26–7.18 (m, 3 H), 6.84
(br. s, 1 H), 3.84 (m, 1 H), 2.95–2.54 (m, 6 H), 1.81–1.63 (m, 7 H),
1.37–1.18 (m, 4 H) ppm.
1
–126.8 (c = 1.0, CHCl3). H NMR (CDCl3, 300 MHz): δ = 7.42–
7.33 (m, 7 H), 7.10 (d, J = 8.75 Hz, 2 H), 4.61 (d, J = 8.74 Hz, 1
H), 4.14 (d, J = 6.59 Hz, 1 H), 3.87 (s, 3 H), 3.72 (t, J = 7.58 Hz,
1 H), 3.56 (t, J = 8.40 Hz, 1 H), 2.04 (br. s, 1 H, NH) ppm. Enantio-
meric excess: 95%, determined by HPLC (Chiralpak AS-H column;
hexane/2-propanol = 50:50; 0.6 mL/min; 230 nm), tR (minor) =
21.6 min, tR (major) = 45.2 min.
(1R,3S,3aR,6aS)-Methyl 3-(4-Methoxyphenyl)-4,6–dioxo-5-phenyl-
octahydropyrrolo[3,4-c]pyrrole-1-carboxylate (4e): This is a known
compound.[4i] The product was obtained according to the general
procedure as described above in 79% yield as a white solid. [α]2D0
=
The catalysts 1d, 1e, and 1f were prepared in a similar manner to
1c.
–7.1 (c = 1.1, CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 7.42–7.29
(m, 5 H), 7.15 (d, J = 7.1 Hz, 2 H), 6.88 (d, J = 8.67 Hz, 2 H), 4.58
(d, J = 8.80 Hz, 1 H), 4.14 (d, J = 6.6 Hz, 1 H), 3.87 (s, 3 H), 3.79
(s, 3 H), 3.72 (t, J = 6.9 Hz, 1 H), 3.53 (t, J = 8.3 Hz, 1 H), 2.04
(br. s, 1 H, NH) ppm. Enantiomeric excess: 96%, determined by
HPLC (Chiralpak AS-H column; hexane/2-propanol = 50:50;
General Procedure for Asymmetric 1,3-Dipolar Cycloaddition of
Azomethine Ylides Catalyzed by Chiral Tertiary Amine Thiourea: A
mixture of imino esters (0.30 mmol), N-arylmaleimides
(0.45 mmol), the catalyst 1c (0.075 mmol), and 4 Å molecular sieves
(300 mg) were stirred in CH2Cl2 (1.0 mL) at –20 °C for 72 h (reac-
tion was monitored by TLC). After evaporation under reduced
pressure, the residue was purified through column chromatography
on silica gel (petroleum ether/ethyl acetate = 1.5:1) to yield pure
products.
0.6 mL/min; 230 nm), tR (minor)
= 29.7 min, tR (major) =
48.5 min.
(1R,3S,3aR,6aS)-Methyl 4,6-Dioxo-5-phenyl-3-(p-tolyl)octahydro-
pyrrolo[3,4-c]pyrrole-1-carboxylate (4f): This is a known com-
Eur. J. Org. Chem. 2011, 4472–4478
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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X.-Y. Xu, L.-X. Wang et al.
FULL PAPER
pound.[4i] The product was obtained according to the general pro-
7.61 Hz, 1 H), 4.14 (d, J = 6.24 Hz, 1 H), 3.93 (s, 3 H), 3.88 (s, 3
H), 3.75 (t, J = 7.78 Hz, 1 H), 3.72 (t, J = 7.90 Hz, 1 H), 2.34 (br.
s, 1 H, NH) ppm. Enantiomeric excess: 87%, determined by HPLC
cedure as described above in 72% yield as a white solid. [α]2D0
=
–147.1 (c = 0.9, CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 7.45 (d,
J = 7.53 Hz, 1 H), 7.39–7.29 (m, 4 H), 7.11 (d, J = 7.48 Hz, 2 H), (Chiralpak AS-H column; hexane/2-propanol = 50:50; 0.6 mL/min;
6.98–6.93 (m, 1 H), 6.89 (d, J = 8.20 Hz, 1 H), 4.73 (t, J = 7.62 Hz,
1 H), 4.16 (t, J = 6.41 Hz, 1 H), 3.88 (s, 3 H), 3.83 (s, 3 H), 3.79–
3.71 (m, 2 H), 2.04 (br. s, 1 H, NH) ppm. Enantiomeric excess:
90%, determined by HPLC (Chiralpak AS-H column; hexane/2-
propanol = 50:50; 0.6 mL/min; 230 nm), tR (minor) = 21.9 min, tR
(major) = 40.5 min.
230 nm), tR (minor) = 21.4 min, tR (major) = 38.8 min.
(1R,3S,3aR,6aS)-Methyl 3-(2-Nitrophenyl)-4,6-dioxo-5-phenylocta-
hydropyrrolo[3,4-c]pyrrole-1-carboxylate (4l): This is a known com-
pound.[4i] The product was obtained according to the general pro-
cedure as described above in 51% yield as a white solid. [α]2D0
=
–1.1 (c = 0.6, CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 8.15–7.38
(m, 3 H), 7.36–7.07 (m, 4 H), 7.05 (d, J = 6.93 Hz, 2 H), 5.10 (d,
J = 8.34 Hz, 1 H), 4.16 (d, J = 6.51 Hz, 1 H), 4.06 (t, J = 8.19 Hz,
1 H), 3.87 (s, 3 H), 3.76 (t, J = 7.2 Hz, 1 H), 2.38 (br. s, 1 H,
NH) ppm. Enantiomeric excess: 70%, determined by HPLC (Chi-
(1R,3S,3aR,6aS)-Methyl 3-(3-Chlorophenyl)-4,6-dioxo-5-phenyloc-
tahydropyrrolo[3,4-c]pyrrole-1-carboxylate (4g): This is a known
compound.[4i] The product was obtained according to the general
procedure as described above in 72% yield as a white solid. [α]2D0
–97.8 (c = 1.0, CHCl3). H NMR (CDCl3, 300 MHz): δ = 7.50 (s, ralpak AS-H column; hexane/2-propanol = 50:50; 0.6 mL/min;
1 H), 7.43–7.15 (m, 6 H), 7.13 (d, J = 7.26 Hz, 2 H), 4.58 (d, J = 230 nm), tR (minor) = 25.8 min, tR (major) = 30.4 min.
=
1
8.82 Hz, 1 H), 4.14 (d, J = 6.48 Hz, 1 H), 3.87 (s, 3 H), 3.73 (t, J =
(1R,3S,3aR,6aS)-Methyl 3-(Naphthalen-1-yl)-4,6-dioxo-5-phenyloc-
7.11 Hz, 1 H), 3.56 (t, J = 8.16 Hz, 1 H), 2.39 (br. s, 1 H, NH) ppm.
tahydropyrrolo[3,4-c]pyrrole-1-carboxylate (4m): This is a known
Enantiomeric excess: 86%, determined by HPLC (Chiralpak AS-
compound.[4i] The product was obtained according to the general
H column; hexane/2-propanol = 50:50; 0.6 mL/min; 230 nm), tR
procedure as described above in 86% yield as a white solid. [α]2D0
=
(minor) = 20.4 min, tR (major) = 40.9 min.
–137.4 (c = 1.4, CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 7.96 (d,
J = 8.26 Hz, 1 H), 7.89–7.78 (m, 3 H), 7.57–7.44 (m, 3 H), 7.32–
7.27 (m, 3 H), 7.02 (d, J = 7.32 Hz, 2 H), 5.09 (d, J = 8.02 Hz, 1
H), 4.06 (d, J = 5.71 Hz, 1 H), 3.89 (s, 3 H), 3.73–3.62 (m, 2 H),
2.05 (br. s, 1 H, NH) ppm. 13C NMR (CDCl3, 75 MHz): δ = 175.1,
(1R,3S,3aR,6aS)-Methyl 3-(3-Bromophenyl)-4,6-dioxo-5-phenyloc-
tahydropyrrolo[3,4-c]pyrrole-1-carboxylate (4h): This is a known
compound.[4i] The product was obtained according to the general
procedure as described above in 85% yield as a white solid. [α]2D0
–89.9 (c = 1.0, CHCl3). H NMR (CDCl3, 300 MHz): δ = 7.65 (s, 173.1, 170.1, 133.4, 122.1, 131.5, 131.1, 129.0, 128.8, 128.6, 128.3,
1 H), 7.45–7.30 (m, 5 H), 7.25–7.22 (m, 1 H), 7.14 (d, J = 8.01 Hz, 126.3, 126.0, 125.6, 125.3, 123.3, 122.3, 61.4, 59.8, 52.2, 48.0,
=
1
2 H), 4.56 (d, J = 8.77 Hz, 1 H), 4.12 (d, J = 6.4 Hz, 1 H), 3.86 (s,
3 H), 3.72 (t, J = 7.3 Hz, 1 H), 3.55 (t, J = 8.3 Hz, 1 H), 2.04
47.9 ppm. Enantiomeric excess: 90%, determined by HPLC (Chi-
ralpak AS-H column; hexane/2-propanol = 50:50; 0.6 mL/min;
(br. s, 1 H, NH), Enantiomeric excess: 90%, determined by HPLC 230 nm), tR (minor) = 25.5 min, tR (major) = 81.3 min.
(Chiralpak AS-H column; hexane/2-propanol = 50:50; 0.6 mL/min;
230 nm), tR (minor) = 22.5 min, tR (major) = 45.1min.
(1R,3S,3aR,6aS)-Methyl 3-(Furan-2-yl)-4,6-dioxo-5-phenyloctahyd-
ropyrrolo[3,4-c]pyrrole-1-carboxylate (4n): The product was ob-
(1R,3S,3aR,6aS)-Methyl 3-(3-Nitrophenyl)-4,6-dioxo-5-phenyloc-
tahydropyrrolo[3,4-c]pyrrole-1-carboxylate (4i): This is a known
compound.[4i] The product was obtained according to the general
tained according to the general procedure as described above in
82% yield as a white solid. [α]2D0 = –63.0 (c = 1.0, CHCl3). 1H NMR
(CDCl3, 300 MHz): δ = 7.45–7.40 (m, 4 H), 7.21 (d, J = 7.10 Hz,
2 H), 6.42–6.35 (m, 2 H), 4.64 (d, J = 8.77 Hz, 1 H), 4.08 (d, J =
procedure as described above in 64% yield as a white solid. [α]2D0
=
–115.2 (c = 0.6, CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 8.33 (s, 6.99 Hz, 1 H), 3.85 (s, 3 H), 3.76 (t, J = 7.54 Hz, 1 H), 3.57 (t, J =
1 H), 8.16–8.13 (m, 1 H), 7.80 (d, J = 7.62 Hz, 1 H), 7.42–7.34 (m, 8.2 Hz, 1 H), 2.59 (br. s, 1 H, NH) ppm. 13C NMR (CDCl3,
4 H), 7.13 (d, J = 7.14 Hz, 2 H), 4.68 (d, J = 8.49 Hz, 1 H), 4.18
75 MHz): δ = 174.7, 173.8, 169.7, 149.3, 142.6, 131.6, 129.1, 128.8,
(d, J = 6.72 Hz, 1 H), 3.87 (s, 3 H), 3.76 (t, J = 7.26 Hz, 1 H), 3.63 126.1, 110.5, 108.3, 62.2, 59.8, 52.5, 49.4, 49.3 ppm. Enantiomeric
(t, J = 8.1 Hz, 1 H), 2.06 (br. s, 1 H, NH) ppm. Enantiomeric ex-
excess: 91%, determined by HPLC (Chiralpak AS-H column; hex-
cess: 85%, determined by HPLC (Chiralpak AS-H column; hexane/
ane/2-propanol = 50:50; 0.6 mL/min; 230 nm), tR (minor) =
2-propanol = 50:50; 0.6 mL/min; 230 nm), tR (minor) = 39.7 min, 20.3 min, tR (major) = 40.3 min.
tR (major) = 64.1 min.
(1R,3S,3aR,6aS)-Methyl 5-(4-Fluorophenyl)-4,6-dioxo-3-phenyloc-
(1R,3S,3aR,6aS)-Methyl 4,6-Dioxo-5-phenyl-3-(m-tolyl)octahydro-
pyrrolo[3,4-c]pyrrole-1-carboxylate (4j): This is a known com-
pound.[4i] The product was obtained according to the general pro-
tahydropyrrolo[3,4-c]pyrrole-1-carboxylate (5b): The product was
obtained according to the general procedure as described above in
84% yield as a white solid. [α]2D0 = –97.3 (c = 1.1, CHCl3). 1H NMR
(CDCl3, 300 MHz): δ = 7.46–7.33 (m, 5 H), 7.14–7.03 (m, 4 H),
cedure as described above in 75% yield as a white solid. [α]2D0
=
–98.1 (c = 1.0, CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 7.41– 4.62 (d, J = 8.73 Hz, 1 H), 4.16 (d, J = 6.60 Hz, 1 H), 3.87 (s, 3
7.31 (m, 3 H), 7.23–7.11 (m, 6 H), 4.57 (d, J = 8.86 Hz, 1 H), 4.12 H), 3.73 (t, J = 7.65 Hz, 1 H), 3.57 (t, J = 8.52 Hz, 1 H), 2.04 (br.
(d, J = 6.49 Hz, 1 H), 3.87 (s, 3 H), 3.71 (t, J = 6.6 Hz, 1 H), 3.53 s, 1 H, NH) ppm. 13C NMR (CDCl3, 75 MHz): δ = 174.9, 173.5,
(t, J = 7.83 Hz, 1 H), 2.34 (s, 3 H), 2.04 (br. s, 1 H, NH) ppm.
Enantiomeric excess: 93%, determined by HPLC (Chiralpak AS-
H column; hexane/2-propanol = 50:50; 0.6 mL/min; 230 nm), tR
(minor) = 17.9 min, tR (major) = 35.1 min.
169.9, 161.2, 136.6, 128.5, 128.0, 127.8, 127.3, 127.0, 116.0, 64.1,
61.8, 52.3, 49.3, 48.2 ppm. HRMS (ESI): calcd. for
C20H17FN2NaO4 [M + Na] 391.1065; found 391.1081. Enantio-
meric excess: 87%, determined by HPLC (Chiralpak AS-H column;
hexane/2-propanol = 50:50; 0.6 mL/min; 230 nm), tR (minor) =
18.5 min, tR (major) = 27.6 min.
(1R,3S,3aR,6aS)-Methyl 3-(2-Methoxyphenyl)-4,6-dioxo-5-phenyl-
octahydropyrrolo[3,4-c]pyrrole-1-carboxylate (4k): This is a known
compound.[4i] The product was obtained according to the general
(1R,3S,3aR,6aS)-Methyl 5-(4-Chlorophenyl)-4,6-dioxo-3-phenyloc-
tahydropyrrolo[3,4-c]pyrrole-1-carboxylate (5c): The product was
obtained according to the general procedure as described above in
procedure as described above in 71% yield as a white solid. [α]2D0
=
–119.5 (c = 1.0, CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 7.45 (d,
J = 7.37 Hz, 1 H), 7.38–7.29 (m, 4 H), 7.11 (d, J = 7.63 Hz, 2 H), 81% yield as a white solid. [α]2D0 = –100.7 (c = 1.2, CHCl3). 1H
6.96 (t, J = 7.46 Hz, 1 H), 6.88 (d, J = 8.21 Hz, 1 H), 4.73 (d, J =
NMR (CDCl3, 300 MHz): δ = 7.44–7.42 (m, 2 H), 7.39–7.32 (m, 5
4476
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4472–4478

Cycloaddition of N-Arylmaleimides to Azomethine Ylides
H), 7.09 (d, J = 8.75 Hz, 2 H), 4.61 (d, J = 8.74 Hz, 1 H), 4.14 (d,
J = 6.59 Hz, 1 H), 3.87 (s, 3 H), 3.72 (t, J = 7.58 Hz, 1 H), 3.56 (t,
113.5, 64.0, 61.7, 52.2, 49.2, 48.1 ppm. HRMS (ESI): calcd. for
C20H17FN2NaO4 [M + Na] 391.1065; found 391.1065. Enantio-
J = 8.4 Hz, 1 H), 2.04 (br. s, 1 H, NH) ppm. 13C NMR (CDCl3, meric excess: 85%, determined by HPLC (Chiralpak AS-H column;
75 MHz): δ = 174.8, 173.3, 169.9, 136.5, 134.2, 130.0, 129.2, 128.5,
127.3, 127.0, 64.1, 61.8, 52.4, 49.3, 48.2 ppm. HRMS (ESI): calcd.
for C20H17ClN2NaO4 [M + Na] 407.0769; found 407.0769. Enan-
tiomeric excess: 92%, determined by HPLC (Chiralpak AS-H col-
umn; hexane/2-propanol = 50:50; 0.6 mL/min; 230 nm), tR (minor)
= 18.3 min, tR (major) = 26.3 min.
hexane/2-propanol = 50:50; 0.6 mL/min; 230 nm), tR (minor) =
17.7 min, tR (major) = 31.3 min.
(1R,3S,3aR,6aS)-Methyl 5-(2-Fluorophenyl)-4,6-dioxo-3-phenyloc-
tahydropyrrolo[3,4-c]pyrrole-1-carboxylate (5h): The product was
obtained according to the general procedure as described above in
73% yield as a white solid. [α]2D0 = –87.6 (c = 0.8, CHCl3). 1H NMR
(CDCl3, 300 MHz): δ = 7.48–7.46 (m, 2 H), 7.39–7.28 (m, 4 H),
7.19–7.07 (m, 3 H), 4.62 (d, J = 8.67 Hz, 1 H), 4.16 (d, J = 6.78 Hz,
1 H), 3.86 (s, 3 H), 3.79 (t, J = 7.38 Hz, 1 H), 3.63 (t, J = 8.37 Hz,
1 H), 2.34 (br. s, 1 H, NH) ppm. 13C NMR (CDCl3, 75 MHz): δ =
174.2, 172.8, 169.9, 158.7, 136.6, 130.9, 129.1, 128.3, 127.0, 124.5,
119.4, 119.3, 116.5, 63.8, 61.6, 52.2, 49.5, 48.3 ppm. HRMS (ESI):
calcd. for C20H17FN2NaO4 [M + Na] 391.1065; found 391.1067.
Enantiomeric excess: 90%, determined by HPLC (Chiralpak AS-
H column; hexane/2-propanol = 50:50; 0.6 mL/min; 230 nm), tR
(minor) = 24.0 min, tR (major) = 42.0 min.
(1R,3S,3aR,6aS)-Methyl 5-(4-Nitrophenyl)-4,6-dioxo-3-phenyloc-
tahydropyrrolo[3,4-c]pyrrole-1-carboxylate (5d): The product was
obtained according to the general procedure as described above in
70% yield as a white solid. [α]2D0 = –73.7 (c = 1.0, CHCl3). 1H NMR
(CDCl3, 300 MHz): δ = 8.23 (d, J = 8.97 Hz, 2 H), 7.45-7.31 (m, 7
H), 4.64 (d, J = 8.85 Hz, 1 H), 4.17 (d, J = 6.48 Hz, 1 H), 3.92 (s,
3 H), 3.77 (t, J = 7.56 Hz, 1 H), 3.61 (t, J = 8.58 Hz, 1 H), 2.04
(br. s, 1 H, NH) ppm. 13C NMR (CDCl3, 75 MHz): δ = 174.4,
172.9, 169.8, 146.7, 136.9, 136.4, 128.6, 126.9, 126.4, 124.9, 124.2,
64.0, 61.8, 52.3, 49.2, 48.1 ppm. HRMS (ESI): calcd. for
C20H17N3NaO6 [M + Na] 418.1010; found 418.1005. Enantiomeric
excess: 73%, determined by HPLC (Chiralpak AS-H column; hex-
ane/2-propanol = 50:50; 0.6 mL/min; 230 nm), tR (minor) =
30.6 min, tR (major) = 41.1 min.
(1R,3S,3aR,6aS)-Methyl 4,6-Dioxo-3-phenyl-5-(o-tolyl)octahydro-
pyrrolo[3,4-c]pyrrole-1-carboxylate (5i): The product was obtained
according to the general procedure as described above in 82% yield
as a white solid. [α]2D0 = –65.6 (c = 0.7, CHCl3). For the major axial
isomer: 1H NMR (CDCl3, 300 MHz): δ = 7.48–7.43 (m, 2 H), 7.39–
7.23 (m, 6 H), 7.01–6.90 (m, 1 H), 4.62 (d, J = 8.13 Hz, 1 H), 4.18
(d, J = 7.38 Hz, 1 H), 3.85 (s, 3 H), 3.78 (t, J = 7.44 Hz, 1 H), 3.64
(t, J = 8.16 Hz, 1 H), 2.30 (br. s, 1 H, NH), 2.22 (s, 3 H) ppm.
HRMS (ESI): calcd. for C21H20N2NaO4 [M + Na] 387.1315; found
387.1329. Enantiomeric excess: 82%, determined by HPLC (Chi-
ralpak AS-H column; hexane/2-propanol = 50:50; 0.6 mL/min;
230 nm), tR (minor) = 15.5 min, tR (major) = 24.4 min.
(1R,3S,3aR,6aS)-Methyl 5-(4-Methoxyphenyl)-4,6-dioxo-3-phenyl-
octahydropyrrolo[3,4-c]pyrrole-1-carboxylate (5e): The product was
obtained according to the general procedure as described above in
74% yield as a white solid. [α]2D0 = –96.8 (c = 1.1, CHCl3). 1H NMR
(CDCl3, 300 MHz): δ = 7.45 (d, J = 6.75 Hz, 2 H), 7.39–7.31 (m,
3 H), 7.04 (d, J = 9.0 Hz, 2 H), 6.88 (d, J = 9.0 Hz, 2 H), 4.65 (d,
J = 8.76 Hz, 1 H), 4.19 (d, J = 6.69 Hz, 1 H), 3.87 (s, 3 H), 3.77
(s, 3 H), 3.72 (t, J = 6.93 Hz, 1 H), 3.58 (t, J = 8.37 Hz, 1 H), 2.05
(br. s, 1 H, NH) ppm. 13C NMR (CDCl3, 75 MHz): δ = 175.2,
173.8, 170.0, 159.2, 136.6, 128.4, 128.3, 127.2, 127.0, 124.2, 114.2,
64.1, 61.7, 55.3, 52.3, 49.3, 48.2 ppm. HRMS (ESI): calcd. for
C21H20N2NaO5 [M + Na] 403.1264; found 403.1246. Enantiomeric
excess: 95%, determined by HPLC (Chiralpak AS-H column; hex-
ane/2-propanol = 50:50; 0.6 mL/min; 230 nm), tR (minor) =
30.1 min, tR (major) = 42.0 min.
(1R,3S,3aR,6aS)-Methyl 5-(Naphthalen-1-yl)-4,6-dioxo-3-phenyloc-
tahydropyrrolo[3,4-c]pyrrole-1-carboxylate (5j): The product was
obtained according to the general procedure as described above in
66% yield as a white solid. [α]2D0 = –70.2 (c = 0.6, CHCl3). For the
major axial isomer: 1H NMR (CDCl3, 300 MHz): δ = 7.89–7.86
(m, 2 H), 7.49–7.18 (m, 10 H), 4.56 (d, J = 7.58 Hz, 1 H), 4.15 (d,
J = 7.69 Hz, 1 H), 3.84 (s, 3 H), 3.74 (t, J = 7.56 Hz, 1 H), 3.63 (t,
J = 7.99 Hz, 1 H), 2.05 (br. s, 1 H, NH) ppm. 13C NMR (CDCl3,
75 MHz): δ = 175.3, 173.9, 170.0, 136.1, 134.3, 129.9, 128.5, 128.3,
128.2, 128.1, 127.1, 127.0, 126.9, 126.5, 125.7, 125.0, 122.8, 64.2,
62.1, 52.2, 49.5, 48.4 ppm. HRMS (ESI): calcd. for C24H20N2NaO4
[M + Na] 423.1315; found 423.1310. Enantiomeric excess: 88%,
determined by HPLC (Chiralpak AS-H column; hexane/2-prop-
anol = 50:50; 0.6 mL/min; 230 nm), tR (minor) = 19.9 min, tR
(major) = 32.9 min.
(1R,3S,3aR,6aS)-Methyl 4,6-Dioxo-3-phenyl-5-(p-tolyl)octahydro-
pyrrolo[3,4-c]pyrrole-1-carboxylate (5f): The product was obtained
according to the general procedure as described above in 85% yield
1
as a white solid. [α]2D0 = –98.2 (c = 1.0, CHCl3). H NMR (CDCl3,
300 MHz): δ = 7.44 (d, J = 6.83 Hz, 2 H), 7.39–7.31 (m, 3 H), 7.18
(d, J = 8.13 Hz, 2 H), 7.02 (d, J = 8.3 Hz, 2 H), 4.59 (d, J =
8.74 Hz, 1 H), 4.13 (d, J = 6.6 Hz, 1 H), 3.86 (s, 3 H), 3.71 (t, J =
7.65 Hz, 1 H), 3.54 (t, J = 7.65 Hz, 1 H), 2.32 (s, 3 H), 2.32 (br. s,
1 H, NH) ppm. 13C NMR (CDCl3, 75 MHz): δ = 175.1, 173.6,
170.0, 138.4, 136.6, 129.5, 128.9, 128.3, 128.2, 127.0, 125.8, 64.1,
61.7, 52.2, 49.3, 48.2, 21.0 ppm. HRMS (ESI): calcd. for
C21H20N2NaO4 [M + Na] 387.1315; found 387.1319. Enantiomeric
excess: 90%, determined by HPLC (Chiralpak AS-H column; hex-
ane/2-propanol = 50:50; 0.6 mL/min; 230 nm), tR (minor) =
18.8 min, tR (major) = 28.1 min.
(1R,3S,3aR,6aS)-Methyl 5-Methyl-4,6-dioxo-3-phenyloctahydropyr-
rolo[3,4-c]pyrrole-1-carboxylate (5k): This is a known compound.[4i]
The product was obtained according to the general procedure as
described above in 75% yield as a white solid. [α]2D0 = –41.8 (c =
0.4, CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 7.33 (m, 5 H), 4.48
(d, J = 8.58 Hz, 1 H), 4.06 (d, J = 6.78 Hz, 1 H), 3.87 (s, 3 H),
3.55 (t, J = 7.41 Hz, 1 H), 3.42 (t, J = 8.28 Hz, 1 H), 2.86 (s, 3 H),
2.05 (br. s, 1 H, NH) ppm. Enantiomeric excess: 30%, determined
by HPLC (Chiralpak AS-H column; hexane/2-propanol = 50:50;
(1R,3S,3aR,6aS)-Methyl 5-(3-Fluorophenyl)-4,6-dioxo-3-phenyloc-
tahydropyrrolo[3,4-c]pyrrole-1-carboxylate (5g): The product was
obtained according to the general procedure as described above in
87% yield as white solid. [α]2D0 = –81.8 (c = 0.8, CHCl3). 1H NMR
(CDCl3, 300 MHz): δ = 7.45–7.31 (m, 6 H), 7.03–6.90 (m, 3 H),
4.62 (d, J = 8.79 Hz, 1 H), 4.15 (d, J = 6.54 Hz, 1 H), 3.87 (s, 3
H), 3.73 (t, J = 7.59 Hz, 1 H), 3.57 (t, J = 8.49 Hz, 1 H), 2.04 (br.
0.6 mL/min; 230 nm), tR (minor)
= 16.4 min, tR (major) =
27.2 min.
Supporting Information (see footnote on the first page of this arti-
s, 1 H, NH) ppm. 13C NMR (CDCl3, 75 MHz): δ = 174.7, 173.2, cle): Experimental procedures, NMR spectra, and HPLC data for
169.9, 162.6, 136.5, 132.6, 130.1, 130.0, 128.4, 126.9, 121.7, 115.3, complexes 4a–n and 5a–k.
Eur. J. Org. Chem. 2011, 4472–4478
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4477

X.-Y. Xu, L.-X. Wang et al.
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Acknowledgments
This work was supported by the National Natural Science Founda-
tion of China (NSFC) (grant numbers 20802075 and 21042006)
and the Chinese Academy of Sciences.
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Received: February 15, 2011
Published Online: June 1, 2011
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