Enantioselective sulfenylation of α-nitroesters catalyzed by diarylprolinols

Article abstract of DOI:10.1016/j.tetlet.2013.11.037

The organocatalytic sulfenylation of α-nitroesters mediated by diaryl-l-prolinols was developed. A range of α-sulfenylated α-nitroesters were obtained in good yields with moderate to good enantioselectivities.

Full text of DOI:10.1016/j.tetlet.2013.11.037

Tetrahedron Letters 55 (2014) 387–389
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Enantioselective sulfenylation of
by diarylprolinols
a-nitroesters catalyzed
a
a
a
a,c,
Ling Fang a,b, , Aijun Lin , Yan Shi , Yixiang Cheng , Chengjian Zhu
⇑
⇑
a School of Chemistry and Chemical Engineering, State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, PR China
b College of Environmental and Biological Engineering, Chongqing Technology and Business University, Chongqing 400067, PR China
c State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
The organocatalytic sulfenylation of a-nitroesters mediated by diaryl-L-prolinols was developed. A range
Received 29 August 2013
Revised 27 October 2013
Accepted 11 November 2013
Available online 19 November 2013
of
a-sulfenylated
a
-nitroesters were obtained in good yields with moderate to good enantioselectivities.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Organocatalysis
Hydrogen bonding
Sulfenylation
a-Nitroesters
Asymmetric
Many optically active sulfur-containing compounds exhibit
pharmaceutical or biological activities, which were also employed
as ligands, auxiliaries, and synthetic intermediates in organic
chemistry.1 Asymmetric introduction of sulfur bonded directly to
a stereogenic center is a challenge, which has attracted attention
from organic chemists.2,3 The former strategy, involving nucleo-
philic process of thiols and thioacetic acids, has proven to be useful
and is well documented in the literature.2 Recently, electrophilic
sulfenylation as a complementary procedure was reported by sev-
eral groups.3 Therefore, development of new methodologies for
constructing this framework with various types of substrates has
loading as parameters. The results are summarized in Table 1.
Investigations into the catalysts (Fig. 1) revealed that diaryl-
L-
prolinols were superior to thioureas with regard to enantioselec-
tivity and catalytic efficiency (entries 1–6). The sulfenylation
product 4aa was isolated in 87% yield with 56% ee in the presence
of catalyst 1b (20 mol % catalyst loading) in CH2Cl2 at room
temperature (entry 2). However, the electronic properties of the
aromatic ring of diarylprolinol had a substantial impact on the
catalysts’ performance. A sharp decrease in catalyst activity was
observed when 1d, bearing an electron-withdrawing group on
the aromatic ring, was tested (entry 4). Solvent screening indicated
that ether was the best choice among aprotic solvents (entries 2
and 7–10). Moreover, lower temperature (0 °C) led to some loss
of catalyst efficiency (from 95% to 47% yield) albeit with a minor
increase in enantioselectivity (entries 8 and 11). Decreasing the
catalyst loading also resulted in diminished yields (entries 12
and 13).
been an active area of research. On the other hand, although
L-pro-
line derivatives have been widely developed in asymmetric organ-
ocatalysis,4 reports related to
L-proline derivatives exploited as
hydrogen bond acceptor are limited so far.5,3e,f Nitro compounds
are valuable precursor for dyes and insecticides,6 however, to our
knowledge, no catalytic process are available for the preparation
of chiral
a-sulfenylated nitro compounds to date. As a continuation
Under the optimal reaction conditions, we then focused on the
of our efforts to exhibit the diversity of the reaction substrates acti-
vated by secondary amines as the H-bond acceptor, herein, we
variation in a-nitroesters and sulfur reagents. The reaction was
conducted with 20 mol % catalyst 1b in ether at room temperature.
wish to report the first asymmetric sulfenylation of
catalyzed by diaryl- -prolinols.
a-nitroesters
As highlighted in Table 2, compared with more sterically hindered
a-nitroesters, improved enantioselectivities (ca. 70% ee) could be
L
A model reaction of 2a and 3a was examined under a set of con-
ditions, with catalyst variety, solvent, temperature, and catalyst
achieved when those with simple structures 2a–c were investi-
gated (entries 1–9). Furthermore, the aryl sulfur reagents afforded
the corresponding products with higher yields and ee values than
benzyl sulfur reagent (entries 4 and 9). When ethyl 2-nitro-2-
phenylacetate 2d was examined in the identical reaction
⇑
Corresponding authors. Tel./fax: +86 25 83594886.
E-mail addresses: lynnf@163.com (L. Fang), cjzhu@nju.edu.cn (C. Zhu).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.11.037

388
L. Fang et al. / Tetrahedron Letters 55 (2014) 387–389
Table 1
Table 2
Optimization of the catalysts and reaction conditions for the enantioselective
sulfenylation of
Organocatalytic asymmetric sulfenylation of a
-nitroestersa
a
-nitroester 2aa
O
O
O
O
R1
RS
R2
1b (20 mol%)
O
O
R1
R2
+
R S
N
O
Me
O
Me
Catalyst 1
Solvent, r.t.
PhS
Et2O, r.t.
+
PhS
N
NO2
OEt
OEt
NO2
O
NO2
NO2
2a-2f
3a-3d
3a: R=Ph;
4
O
4aa
2a: R1=Me, R2=Et;
2b: R1=Et, R2=Et;
2c: R1=Me, R2=Me;
2d: R1=Ph, R2=Et;
2a
3a
3b: R=pMe-Ph;
3c: R=pCl-Ph
3d: R=PhCH2
Entry
Solvent
Catalyst
Yieldb (%)
eec (%)
2e: R1=Et, R2=2,6-(CH3)2C6H3;
1
2
3
4
5
6
7
8
9
10
11
12
13
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Hexane
Et2O
1a
1b
1c
1d
1e
1f
1b
1b
1b
1b
1b
1b
1b
94
87
75
24
56
22
—
14
5
69
72
70
69
75
72
68
2f: R1=Et, R2=t-Bu;
—
Entry
1
2
Product 4
Yieldb (%)
95
eec (%)
d
e
47
52
88
95
91
80
47
80
68
O
Me
S
4aa
2a
72
OEt
O
NO2
MTBEf
Toluene
Et2Og
Me
S
4ab
2
3
2a
2a
93
80
67
63
OEt
Et2Oh
Et2Oi
NO2
O
a
Reaction conditions: 3a (0.22 mmol) was added to the solution of
a
-nitroester
Me
S
4ac
2a (0.2 mmol) and catalyst (0.04 mmol, 20 mol %) in solvent (2 mL) at room tem-
perature and stirred for 24 h.
OEt
NO2
O
b
Isolated yields.
Determined by chiral HPLC analysis.
<5% Yield.
Not determined.
MTBE = methyl tert-butyl ether.
Reaction ran at 0 °C.
10 mol % of catalyst 1b was used.
5 mol % of catalyst 1b was used.
Cl
c
d
Me
4ad
4ba
S
e
4
5
6
7
8
2a
2b
2b
2c
2c
67
90
96
97
98
40
67
60
67
64
OEt
f
NO2
O
g
h
Et
i
S
OEt
NO2
S
O
1a, Ar = Ph
Ar
Et
1b, Ar = 3,5-(CH3)2C6H3
1c, Ar = 4-CH3OC6H4
1d, Ar = 3,5-(CF3)2C6H3
4bc
Ar
N
H
OEt
HO
NO2
Cl
O
Me
NO2
S
CF3
CF3
S
4ca
OMe
S
S
N
H
N
H
CF3
N
H
N
CF3
H
O
NH
N
Me
1e
1f
4cc
OMe
NO2
O
Figure 1. Catalysts employed in this reaction.
Cl
Me
4cd
conditions, it nearly completely converted into ethyl benzoate7 and
no sulfenylation product was isolated (entries 10).8 Possibly due to
the conjugative effects of the adjacent aryl group, the carbon-cen-
tered anion intermediate formed under basic medium underwent
rearrangement prior to electrophilic substitution. Interestingly,
increasing the bulky hindrance of the substrate ester moiety by
introducing tert-butyl or 2,6-dimethylphenyl, reduced the reaction
stereoselectivity (entries 11 and 12). In contrast to the general lit-
eratures related to asymmetric catalysis, the results indicated that
steric effect of the substrate was not the significant factor for reac-
tion enantioselectivity in this catalytic system. Nevertheless, ethyl
2-cyanopropanoate 5 only afforded the sulfenylation product 6
with 30% ee (entry 13). These results revealed that the structure
of nitroesters had a substantial impact on reaction enantioselectiv-
ity. Supported by the experiment results and the analogy to sulfe-
nylation of b-ketoesters,3e it is suggested that the reaction
intermediate was formed by the strong interaction of hydrogen-
bonding between substrate with nitro group and the catalyst
although the reaction mechanism is not clear.
S
9
2c
60
—
32
—
OMe
NO2
10
2d
4da —
O
Et
S
S
4ec
11
2e
78
10
O
NO2
Cl
O
Et
4fc
OBut
12
13
2f
5
84
81
28
30
NO2
Cl
O
Me
CN
S
6
OEt
a
Reaction conditions: 3 (0.22 mmol) was added to the solution of
(0.2 mmol) and catalyst 1b in Et2O (2 mL) at room temperature, and stirred for 24–
a-nitroester
36 h.
b
Isolated yields.
c
Determined by chiral HPLC analysis.
In summary, we have developed a facile protocol for prepara-
a-sulfenylated a
-nitroesters9 in moderate-to-good ee’s,
as hydrogen bond acceptor for more substrates with a
hydrogen atom.
a-acidic
tion of
and this is another example that
L-proline derivatives could serve

L. Fang et al. / Tetrahedron Letters 55 (2014) 387–389
389
Chen, W.; Xie, M.; Liu, X.; Lin, L.; Feng, X. Org. Lett. 2012, 14, 2726–2729; (e)
Fang, L.; Lin, A.; Hu, H.; Zhu, C. Chem. Eur. J. 2009, 15, 7039–7043; (f) Lin, A.;
Fang, L.; Zhu, X.; Zhu, C.; Cheng, Y. Adv. Synth. Catal. 2011, 353, 545–549; (g) Li,
X.; Liu, C.; Xue, X.-S.; Cheng, J.-P. Org. Lett. 2012, 14, 4374–4377.
Acknowledgments
We gratefully acknowledge the National Natural Science
Foundation of China (21172106 and 21074054) and the National
Basic Research Program of China (2010CB923303) for their finan-
cial support. Research Fund for the Doctoral Program of Higher
Education of China (20120091110010) is also acknowledged.
4. For reviews, see: (a) Mukherjee, S.; Yang, J. W.; Hoffmann, S.; List, B. Chem. Rev.
2007, 107, 5471–5569; (b) Jensen, K. L.; Dickmeiss, G.; Jiang, H.; Albrecht, Ł.;
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(b) Lattanzi, A. Adv. Synth. Catal. 2006, 348, 339–346; (c) Russo, A.; Lattanzi, A.
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Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.
11.037.
6. (a) Metcalf, R. L. Organic Insecticides: Their Chemistry and Mode of Action;
Interscience: New York, 1955; (b) Martin, H. EP 0114705, 1984.
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NMR analysis: Wang, A.; Jiang, H. J. Am. Chem. Soc. 2008, 130, 5030–5031.
8. Similar phenomena were also observed in these literatures: (a) Ramírez, J.;
Huber, D. P.; Togni, A. Synlett 2007, 1143–1147; (b) Han, B.; Liu, Q.-P.; Li, R.; Tian,
X.; Xiong, X.-F.; Deng, J.-G.; Chen, Y.-C. Chem. Eur. J. 2008, 14, 8094–8097.
References and notes
9. General procedure for the organocatalytic sulfenylation of
a-nitroesters: A solution
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of catalyst 1b (12.4 mg, 0.04 mmol) and -nitroesters 2 (0.2 mmol) in dry ether
a
(2 mL) was stirred for 5 min at room temperature before the sulfur reagent 3
(0.22 mmol) was added, and the resulting mixture was stirred for 24-36 h. The
crude reaction mixture was diluted with ethyl acetate and then directly purified
by flash chromatography on silica gel (petroleum ether/EtOAc) to afford the
corresponding product 4.
2. For selected examples, see: (a) McDaid, P.; Chen, Y.; Deng, L. Angew. Chem., Int.
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3. For selected examples, see: (a) Zhao, G.-L.; Rios, R.; Vesely, J.; Eriksson, L.;
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Ethyl 2-nitro-2-(phenylthio)propanoate (4aa): Colorless oil; yield: 95% (48.4 mg);
72% ee [HPLC (Chiralcel OJ–H, hexane/i-PrOH = 90:10, flow rate 0.5 ml/min),
retention time, 19.8 min (major), 23.2 min (minor)]. ½ ꢀ ¼ ꢁ12:9 (c 0.45,
a 2D5
EtOAc). 1H NMR (300 MHz, CDCl3): d 7.64–7.61 (m, 2H), 7.50–7.45 (m, 1H),
7.42–7.37 (m, 2H), 4.20 (dq, J = 10.8, 7.2 Hz, 1H), 4.14 (dq, J = 10.8, 7.2 Hz, 1H),
1.95 (s, 3H), 1.18 (t, J = 7.2 Hz, 3H) ppm. 13C NMR (75 MHz, CDCl3): d 164.4,
137.0, 130.8, 129.2, 127.8, 99.1, 63.4, 23.7, 13.5 ppm. EI-MS: m/z 208 (35)
[MꢁHNO2]+, 135 (100).