Salan-vanadium catalyzed enantioselective desymmetrization of meso-epoxides with aromatic thiols

Article abstract of DOI:10.2174/157017809788489990

The first example of salan-vanadium catalyzed enantioselective ring-opening of meso-epoxides has been reported, which furnished β-hydroxy sulfides in good yields and moderate enantioselectivities.

Full text of DOI:10.2174/157017809788489990

Letters in Organic Chemistry, 2009, 6, 329-331
329
Salan-Vanadium Catalyzed Enantioselective Desymmetrization of
meso-Epoxides with Aromatic Thiols
Jiangtao Sun*,a, Weijin Gub, Yijun Huanga, Xu Pana and Chengjian Zhu*,a,c
aSchool of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China
bDepartment of Applied Chemistry, Nanjing Normal University, Nanjing 210097, China
cState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sci-
ences, Shanghai 200032, China
Received October 09, 2008: Revised April 05, 2009: Accepted April 11, 2009
Abstract: The first example of salan-vanadium catalyzed enantioselective ring-opening of meso-epoxides has been re-
ported, which furnished ꢀ-hydroxy sulfides in good yields and moderate enantioselectivities.
Keywords: Vanadium, Ring-opening, Thiols, Epoxides, Enantioselectivity, Asymmetric catalysis.
INTRODUCTION
enantioselective addition of thiols to meso-epoxides cata-
lyzed by chiral salan-vanadium complexes.
Since vanadium can exist in oxidation states ranging
from -3 to +5, this versatility permits vanadium compounds
can be used in a wide range of organic reactions by control-
ling their redox potentials [1]. Generally, chiral vanadium
complexes have been used mainly on asymmetric oxidation
reactions, such as asymmetric epoxidation [2], asymmetric
sulfoxidation [3] and kinetic resolutions of alcohols with
molecular oxygen [4]. However, a few reports concerned
RESULTS AND DISCUSSION
The synthesis of chiral ligands is straightforward as
shown in Scheme 1. The ligands can be easily prepared from
commercially available salen ligands 1a and 1b in high
chemical yields. Choosing cyclohexene oxide as the model
R3
R3
n-BuLi, THF,
0 oC
NH HN
N
N
N
N
NaBH4, MeOH
R1
R1
R1
OH HO
OH
HO
R1
R1
OH
HO
R1
R2
R2
1a R1 = R2 = H
1b R1 = R2 = t-Bu
R2
R2
R2
R2
2a R1 = R2 = H
2b R1 = R2 = t-Bu
3a R1 = R2 = H, R3 = CH3
3b R1 = R2 = H, R3 = -CH2Ph
Scheme 1.
about other types of reactions [5]. On the other hand, al-
though the enantioselective desymmetrization of meso-
epoxides with nucleophiles has proven to be a valuable tool
for the straightforward synthesis of enantiomerically highly
enriched 1,2-difunctionalized organic compounds [6], the
use of thiols as nucleophiles is still relatively unexplored and
only a few of examples have been reported [7]. Recently,
chiral salan [N,N’-alkyl-bis(salicylamine)] ligands have been
widely investigated in various asymmetric reactions with
high enantioselectivities [8, 9]. Herein we wish to report the
substrate, we initially investigated the ring-opening reaction
with thiophenol catalyzed by the in situ formation of chiral
vanadium complexes (Table 1). From the summarized re-
sults, we can find that VO(OiPr)3-2a afforded the best results
in terms of reactivity and selectivity (entry 7) [11]. Among
the five solvents investigated, toluene proved to be the best
one. Further investigation on the reaction temperature
o
showed that 0 C was the preferred temperature. The reac-
o
tions were finished in 36 h at 0 C whereas -40 oC gave very
low yield (entry 15). High yield but low enantioselectivity
were obtained when the reaction was carried out at room
temperature (entry 16).
*Address correspondence to these authors at the School of chemistry and
chemical engineering, Nanjing University, Nanjing 210093, China; Fax:
+86-25-83317761; E-mail: jtsun08@gmail.com; cjzhu@nju.edu.cn
Next, the ring-opening reactions of various meso-
epoxides have been investigated under the optimized reac-
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330 Letters in Organic Chemistry, 2009, Vol. 6, No. 4
Sun et al.
Table 1. Asymmetric Ring-Opening of Cyclohexene Oxide with Thiophenola
OH
S
solvent, 0 oC
PhSH
O
+
catalyst
Entry
Vanadium
Ligand
Solvent
Yield (%)b
Ee (%)c
1
2
VO(acac)2
VO(acac)2
VO(acac)2
VO(acac)2
VO(OiPr)3
VO(OiPr)3
VO(OiPr)3
VO(OiPr)3
VO(OiPr)3
VO(OiPr)3
VO(OiPr)3
VO(OiPr)3
VO(OiPr)3
VO(OiPr)3
VO(OiPr)3
VO(OiPr)3
1a
1b
2a
2b
1a
1b
2a
2b
3a
3b
2a
2a
2a
2a
2a
2a
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
CH2Cl2
CH3CN
THF
43
35
33
27
51
46
85
67
63
52
82
91
90
37
24
83
<5
<5
37
24
16
8
3
4
5
6
7
71
23
42
26
54
17
32
46
69
52
8
9
10
11
12
13
14
15d
16e
Hexane
Toluene
Toluene
aReaction conditions: 1 mmol cyclohexene oxide, 1.2 mmol PhSH, 10 mol% vanadium compounds, 15 mol% chiral ligand, 0 oC; bIsolated yield; cDetermined by HPLC analysis using
a Daicel Chiracel OD-H column or OB-H column; dThe reaction was carried out at -40 oC; eThe reaction was carried out at 25 oC.
Table 2. Asymmetric Ring-Opening of meso-Epoxides with Aromatic Thiolsa
10 mol% VO(OiPr)3
R
R
OH
S
R
15 mol% 2a
toluene, 0 oC
O
R'
SH
+
R'
R
5a R' = H
5b R' = CH3
5c R' = Cl
4a R = -(CH2)4-
4b R = -(CH2)3-
4c R = Ph
6
Yield (%)b
Ee (%)c
Product
Entry
Epoxide
Thiol
1
2
3
4
5
6
7
8
4a
4b
4c
4a
4b
4c
4a
4c
5a
5a
5a
5b
5b
5b
5c
5c
6aa
6ba
6ca
6ab
6bb
6cb
6ac
6cc
85
82
68
84
76
64
72
77
71
66
52
72
74
38
67
56
aReaction conditions: 1 mmol epoxide, 1.2 mmol aromatic thiol, 10 mol% VO(OiPr)3, 15 mol% 2a , toluene, 0 oC, 36 h; bIsolated yield; cDetermined by HPLC analysis using a Daicel
Chiracel OD-H column or OB-H column.
tion conditions [10]. The results were summarized in Table
2. All reactions proceeded smoothly to afford the desired
hydroxy sulfides in moderate yields (from 54 to 84%) and
moderate enantioselectivities (from 32 to 74%). The highest
ee value was obtained when 4a was used as substrate and
thiol 5b as nucleophile (entry 6). Amongst all of the three

Salan-Vanadium Catalyzed Enantioselective Desymmetrization
Letters in Organic Chemistry, 2009, Vol. 6, No. 4
331
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thiol afforded the corresponding products in highest enanti-
oselectivities.
CONCLUSION
In summary, the asymmetric ring-opening reaction of
meso-epoxides with thiols catalyzed by salan-vanadium
complexes has been realized. ꢀ-hydroxy sulfides were ob-
tained in moderate yields (up to 85%) and moderate enanti-
oselectivities (up to 74% ee). Currently we are extending the
application of chiral vanadium compounds to other reactions
and studying their synthetic applications.
[8]
[9]
(a) Saito, B; Katsuki, T. Angew. Chem. Int. Ed., 2005, 44, 4600; (b)
Egami, H.; Katsuki, T. Synlett, 2008, 1543; (c) Egami, H.; Katsuki,
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A general procedure of the asymmetric ring-opening of meso-
epoxide with thiol: To a stirred solution of 2a (0.15 mmol) in tolu-
ene (3.0 mL) under argon was added VO(OiPr)3 (0.1 mmol). The
resulting mixture was stirred at room temperature for 1 h, then
cooled to 0°C, epoxide (1.0 mmol) and thiol (1.2 mmol) was added.
After stirred at 0°C for 36 h, the reaction mixture was filtered
through a silica gel and washed with CH2Cl2. The solvent was re-
moved under reduced pressure and the residue was purified by
flash column chromatography to furnish the corresponding hy-
droxyl sulfides. The enantiomeric purity was determined by HPLC
analysis using a Daicel Chiracel OD-H column or OB-H column.
Ligand 3b was synthesized according to the following procedure:
Under an argon atmosphere, 1.5 mL anhydrous DMF was added
dropwise into a mixture of NaH (1.5 g, 25 mmol) and 15 mL anhy-
drous THF in a Schlenk tube. Then the mixture was stirred for 10
min and 2a (1.62 g, 5 mmol) was added. After stirred for another
30 min, bromobenzyl (1.3 mL, 11 mmol) was added and the mix-
ACKNOWLEDGEMENTS
We gratefully acknowledge the National Natural Science
Foundation of China (20672053, 20832001) and the National
Basic Research Program of China (2007CB925103) for their
financial support. The Program for New Century Excellent
Talents in the University of China (NCET-06-0425) is also
acknowledged.
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1
CH2Cl2). H-NMR (300MHz, CDCl3): ꢂ 1.10-1.37 (m, 4H), 1.69-
1.82 (m, 2H), 2.07-2.10 (m, 1H), 2.23-2.29 (m, 1H), 2.60 (s, 2H),
3.41-3.46 (d, 1H), 3.55-3.59 (d, 1H), 3.75-3.82 (t, 3H), 3.98-4.02
(d, 1H), 4.96-5.11 (m, 4H), 6.91-6.93 (m, 4H), 7.21-7.27 (m, 3H),
7.29-7.34 (m, 3H), 7.40-7.47 (m, 10H). MS (EI): 505(M-1, 16),
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