Asymmetric ring-opening of cyclohexene oxide with mercaptan (thiophenols) catalyzed by chiral Schiff base/Ti(OPr-i)4 or (-)-(S)-binaphthol/Ti(OPr-i)4

Article abstract of DOI:10.1080/10426500307840

New chiral Schiff base ligands 1-4 were synthesized starting from (+)-camphor and (+)-1-(4-nitrophenyl)-2-amino-1,3-propanediol, and their application in asymmetric ring-opening of cyclohexene oxide using mercaptan (thiophenols) as nucleophiles was investigated. The aymmetric ring-opening of cylohexene oxide catalyzed respectively by chiral Schiff bases 1-4/Ti(OPr-i)₄ and (-)-(S)-1,1′-binaphthalene-2,2′-diol 5/Ti(OPr-i)₄ complex afforded the corresponding chiral β-hydroxysulfides 6-10 in lower to good yield with lower to moderate ee values. Moreover, the using of (-)-(S)-1,1′-binaphthalene-2,2′-diol as ligand led to better chiral induction effect.

Full text of DOI:10.1080/10426500307840

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Asymmetric Ring-Opening of Cyclohexene Oxide with
Mercaptan (Thiophenols) Catalyzed by Chiral Schiff
Base/Ti(OPr- i ) 4 or (-)-(S)-Binaphthol/Ti(OPr- i ) 4
a
a
a
a
a
Zhenghong Zhou , Zhaoming Li , Kangying Li , Zhuohong Yang , Guofeng Zhao , Lixin
a
a
a
Wang , Qilin Zhou & Chuchi Tang
a
State Key Laboratory of Elemento-Organic Chemistry, Tianjin, China
Version of record first published: 27 Oct 2010.
To cite this article: Zhenghong Zhou , Zhaoming Li , Kangying Li , Zhuohong Yang , Guofeng Zhao , Lixin Wang , Qilin Zhou
Chuchi Tang (2003): Asymmetric Ring-Opening of Cyclohexene Oxide with Mercaptan (Thiophenols) Catalyzed by Chiral
Schiff Base/Ti(OPr- i ) 4 or (-)-(S)-Binaphthol/Ti(OPr- i ) 4, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:8,
771-1779
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Phosphorus, Sulfur, and Silicon, 178:1771–1779, 2003
Copyright ꢀC Taylor & Francis Inc.
ISSN: 1042-6507 print
DOI: 10.1080/10426500390221104
ASYMMETRIC RING-OPENING OF CYCLOHEXENE
OXIDE WITH MERCAPTAN (THIOPHENOLS)
CATALYZED BY CHIRAL SCHIFF BASE/Ti(OPr-i)
4
OR (−)-(S)-BINAPHTHOL/Ti(OPr-i)4
Zhenghong Zhou, Zhaoming Li, Kangying Li, Zhuohong Yang,
Guofeng Zhao, Lixin Wang, Qilin Zhou, and Chuchi Tang
State Key Laboratory of Elemento-Organic Chemistry,
Tianjin, China
(
Received October 29, 2002; accepted March 14, 2003)
New chiral Schiff base ligands 1–4 were synthesized starting from
(
+)-camphor and (+)-1-(4-nitrophenyl)-2-amino-1,3-propanediol, and
their application in asymmetric ring-opening of cyclohexene oxide us-
ing mercaptan (thiophenols) as nucleophiles was investigated. The
aymmetric ring-opening of cylohexene oxide catalyzed respectively
ꢁ
by chiral Schiff bases 1–4/Ti(OPr-i) and (−)-(S)-1,1 -binaphthalene-
4
ꢁ
2
,2 -diol 5/Ti(OPr-i) complex afforded the corresponding chiral β-
4
hydroxysulfides 6–10 in lower to good yield with lower to moderate
ꢁ
ꢁ
ee values. Moreover, the using of (−)-(S)-1,1 -binaphthalene-2,2 -diol as
ligand led to better chiral induction effect.
Keywords: Asymmetric ring opening; binaphthol; chiral Schiff base;
cyclohexane epoxide; thiophenols (mercaptan)
The stereoselective ring-opening of meso-epoxides with various nucle-
ophiles is an important transformation in organic synthesis because it
is a powerful strategy for the formation 1,2-bifunctionalized systems,
and at the same time establishes two contiguous stereogenic centers.
A wide variety of nucleophiles are used in the aforementioned ring-
opening reaction.1 Among them, sulfur nucleophiles are important
and the most reported sulfur nucleophiles are alkane- and arene-thiols.
This asymmetric ring-opening of meso-epoxides with mercaptan or
,2
We are grateful to the National Nature Science Foundation of China (No. 20272025)
and Ph.D. Programs Foundation of Ministry of Education of China for generous financial
support.
Address correspondence to Chuchi Tang, State Key Laboratory of Elemento-Organic
Chemistry, Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071,
P.R. China. E-mail: c.c.tang@eyou.com
1
771

1
772
Z. Zhou et al.
thiophenols catalyzed by a chiral metal reagent affrods the correspond-
ing chiral β-hydroxysulfides. Yamashita has realized the enantioselec-
tive ring-opening of epoxides with mercaptans catalyzed by Metal(II)
3
d-tartarate. However, this suffered from long reaction time and harsh
reaction conditions as well as the low enantioselectivity. Although high
enantioselectivity was obtained by Shibasaki and Jacobsen using Ga/Li
bis(binaphthoxide) complex and salen(Cr) as the catalysts, respectively,
4
the ring-opening reagents were limited to tert-butyl mercaptan and
5
dimercapto compounds. Hou has investigated salen Ti(IV) catalyzed
ring-opening of epoxides with mercaptan or thiophenol. The correspond-
6
ing ring-opening products were obtained only with moderate ee values.
Herein, we report the asymmetric ring-opening of cyclohexene oxide
with mercaptan (thiophenol) catalyzed by 4 recently synthesized Schiff
ꢁ
ꢁ
bases 1–4 and (d)-(S)-1,1 -binaphthalene-2,2 -diol 5 in the presence of
Ti(OPr-i)4.
EXPERIMENTAL
1H and 31P NMR were recorded in CDCl3 as solvent on a Brucker AC-
1
P200 instrument using TMS as internal standard for H NMR and
8
5% H3PO4 as external standard for 31P NMR. Elemental analyses
were conducted on MT-3 CHN automatic analyzer. Melting points were
determined on XT-4 apparatus. Specific rotations were measured on a
Perkin Elmer 241MC polarimeter. All the temperatures were uncor-
rected. All the solvents were dried and redistilled according to the lit-
erature. Ti(OPr-i)4 was Fluka reagent.
Preparation of Chiral Schiff Base
(
+)-cis-1,2,2,-Trimethylcyclopentane-1,3-dicarboxylic
7
Acid
.
A mixture of (1R)-(+)-camphor (19.0 g, 0.125 mmol), FeSO4 7H2O
(
1.2 g, 0.0036 mmol), HNO3 (180 mL, 65–68%) and 85 mL of water was
◦
refluxed at 100–105 C for 30 h, then the resulting was cooled to room
temperature, the white solid precipitate was collected by filteration and
washed twice with water to give desired product 12.2 g, yield: 49%, m.p.
◦
25
D
2
02–205 C, [α] = +44 (c 10, EtOH).
(
+)-cis-1,2,2-Trimethylcyclopentane-1,3-diamine7
To a mixture of (+)-cis-1,2,2,-trimethylcyclopentane-1,3-dicarboxylic
acid (20.3 g, 0.1 mmol), concentrated H2SO4 (60 mL) and 200 mL of
chloroform was added NaN3 (18.6 g, 0.286 mmol) at intervals until gas

Asymmetric Ring-Opening of Cyclohexene Oxide
1773
evolution ceased. The resulting solution was cooled to room tempera-
ture and adjusted to pH > 14 with saturated NaOH. The solution was
deposited overnight and filtered, and washed with CHCl3 (2 × 30 mL).
The organic phase was separated and the aqueous layer was extracted
with CHCl3 (2 × 30 mL). The combined organic phase was dried over an-
hydrous MgSO4, then the solvent was removed under reduced pressure
to afford crude product 12.2 g, yield: 86%.
Preparation of Compound 1 (Typical Procedure)7
A mixture of salicylaldehyde (2.44 g, 20 mmol), (+)-cis-1,2,2-
trimethylcyclopentane-1,3-diamine (1.42 g, 10 mmol), p-toluenesulfonic
acid (0.01 g) and 40 mL of toluene was stirred under reflux for 2 h. Af-
ter removal of solvent, the crude product was recrystallized from ethyl
◦
25
acetate to give 2.80 g of 1 as yellow solid. M.p. 159–161 C; [α] = +34
D
1
(
c 2, CHCl3); H NMR (δ, ppm): 0.95 (s, 3H, CH3), 0.97 (s, 3H, CH3),
1
.36 (s, 3H, CH3), 2.15 (m, 4H, 2CH2), 3.71 (t, 1H, CH, J = 6.84 Hz),
7.11 (m, 8H, Ar-H), 8.45 (s, 2H, OH). Elemental analysis calculated for
C22H26N2O2: C, 75.36; H, 7.49; N, 7.99. Found: C, 75.15; H, 7.50; N,
.88.
7
Preparation of Compound 2
◦
25
D
Yellow solid, 80% yield, m.p. 137–139 C; [α] = +41.9 (c 1.5, CHCl3);
1
H NMR (δ, ppm): 0.96 (s, 6H, CH3), 1.32 (s, 3H, CH3), 1.35 (s, 9H, Bu-
H), 1.45 (s, 9H, Bu-H), 2.28 (m, 7H, CH3 and 2CH2), 3.54 (t, 1H, CH,
J = 7.26 Hz), 7.20 (m, 4H, Ar-H), 8.34 (s, 1H, OH), 13.24 (s, 1H, OH).
Elemental analysis calculated for C32H46N2O2: C, 78.32; H, 9.45; N,
5.71. Found: C, 78.14; H, 9.36; N, 5.45.
Preparation of Compound 3
◦
25
D
Yellow solid, 77% yield, m.p. 237–240 C; [α] = +37.7 (c 1, CHCl3);
1
H NMR (δ, ppm): 0.95 (s, 3H, CH3), 0.97 (s, 3H, CH3), 1.36 (s, 3H, CH3),
2.04 (m, 4H, 2CH2), 3.68 (t, 1H, CH, J = 7.02 Hz), 7.29 (m, 4H, Ar-H),
8.24 (s, 2H, OH). Elemental analysis calculated for C22H22Cl4N2O2: C,
54.12; H, 4.54; N, 5.74. Found: C, 54.13; H, 4.28; N, 5.73.
Preparation of Compound 4
A mixture of salicylaldehyde (1.20 g, 20 mmol), (+)-1-(4-nitrobenzyl)-
2
-amino-1,3-propanediol (2.10 g, 10 mmol), p-toluenesulfonic acid
(
0.01 g) and 30 mL of toluene was stirred under reflux for 7 h. After
cooling to room temperature, the precipitate formed was collected by fil-
tration and washed with ether to give 3.00 g of the desired Schiff base
◦
25
1
4
. 97% yield, m.p. 184–186 C; [α]D = +308.4 (c 2, CHCl3); H NMR

1
774
Z. Zhou et al.
(
δ, ppm): 3.63 (m, 3H, CH2 and CH), 5.19 (s, 1H, CH), 6.84 (d, 2H,
Ar-H, J = 7.87 Hz), 7.25 (d, 2H, Ar-H, J = 3.17 Hz), 7.69 (d, 2H, Ar-H,
J = 8.55 Hz), 8.15 (d, 2H, Ar-H, J = 4.47 Hz), 8.32 (s, 1H, OH). Elemental
analysis calculated for C16H16N3O5: C, 60.75; H, 5.10; N, 8.86. Found:
C, 60.70; H, 4.95; N, 8.75.
Asymmetric Ring-Opening Reaction of Cyclohexane
Epoxide with Mercaptans (Or Thiophenols)
To a 10 mL anhydrous flask was added 2 mL of solvent, 0.3–1 mmol
of chiral ligands (1:1 of Schiff base or (S)-binaphthol/Ti(OPr-i)4) under
a nitrogen atomosphere. The mixture was stirred at room tempera-
ture for 1 h, then 1 mmol of mercaptan (or thiophenols) and 1 mmol
of cyclohexane epoxide were introduced. The resulting mixture was
stirred at room temperature monitored by TLC. After removal of the
solvent, the crude product was purified by thin layer chromatogra-
phy on silica gel (300–400 mesh, petroleum ether/ethyl acetate as elu-
ent) to afford ring-opening products 6–10. (See Table III for data for
compounds 6–10).
RESULTS AND DISCUSSION
The Synthesis of Chiral Schiff Base
The chiral Schiff bases 1–3 were synthesized by successive oxidation,
aminaton, and imination of (+)-camphor according to the method re-
7
ported by our group. Because (+)-cis-1,2,2-trimethylcyclopentane-1,3-
diamine was difficult to purify, it was used directly in the reaction with
salicylaldehyde or its derivatives to produce desired ligands 1–3.
(
+)-1-(4-nitrobenzyl)-2-amino-1,3-propanediol was an easily avail-
able by-product in the manufacture of chloromycetin. It was reacted
with salicylaldehyde catalyzed by p-toluenesulfonic acid to afford Schiff

Asymmetric Ring-Opening of Cyclohexene Oxide
1775
base 4 in excellent yield.
ꢀ
ꢀ
(
−)-(S)-1,1 -Binaphthalene-2,2 -diol 5
Highly enantiomeric pure 5 could be obtained with high yield according
to our recently reported method using L-menthol as resolving agent via
the cyclic phosphite.8
Ring-Opening Reaction of Epoxides Catalyzed by Chiral Schiff
Base 1–5/Ti(OPr-i)4
The asymmetric ring-opening of cyclohexene epoxide with 4-
methylthiophenol catalyzed by 30 mol% of 4 chiral Schiff bases in n-
hexane was investigated. All the results are summarized in Table I.
As shown in Table I, the reaction temperature had a modest influence
on the enantioselectivity and yield of the ring-opening reaction. The
◦
enantioselectivity and yield at −20 C (entry 1) were lower than those
◦
◦
at 0 C. Similarly, the catalytic effect at 20 C was slightly decreased
compared with that at 0 C. Therefore, the optimal reaction temperature
◦
◦
was 0 C.
The structure of the catalysts also was found to by an essential factor
to the enantioselectivity and yield of the reaction. The best catalyst was
the Schiff base which has bulky group substituted at the ortho-position
of the hydroxy in the benzene ring. For example, because of the bulky
tert-butyl group the catalytic effect of ligand 2 was much better than
those of ligands 3, 4, 1, which have only small groups, such as hydrogen,
chloro substituted at the ortho-position. The yield and enantioselectiv-
ity of ligand 2 were 78% and 36% ee respectively. However, the latter
had only 45–34% yield and 11–3% ee.

1
776
Z. Zhou et al.
TABLE I Ring-Opening of Cylohexene Oxide Catalyzed by Chiral Schiff
Bases 1–4/Ti(OPr-i)
4
◦
Yield (%)a
25
ee%b
ee%c
Entry
Ligands
Temp. ( C)
[α] (c 1, CH2Cl2)
D
1
2
3
4
5
6
2
2
2
1
3
4
−20
0
20
0
72
78
75
35
34
45
+17.3
+22.2
+22.1
+6.1
25
32
32
9
3
10
26
36
0
0
+2.0
3
11
+7.1
a
Isolated yield.
b
20
D
Determined by the comparison of sepecific rotation values, [α] +42.7 (c 0.75,
6
CH2Cl2) with 62%ee.
cDetermined by HPLC with chiral column (Chiralcel OD).
Comparison of specific rotation value with those reported in
3
b
literature, the absolute configuration of ring-opening products 6 could
be determined as 1S,2S. (Other data of compounds 6 are shown in
Table III).
Ring-Opening Reaction of Epoxides Catalyzed
by (−)-(S)-Binaphthol 5/Ti(OPr-i)4
The catalytic effect of (−)-(S)-binaphthol/Ti(OPr-i)4 was examined using
benzyl mercaptan or substituted thiophenols as ring-opening reagents
and cyclohexene epoxide as substrate. All the results are summarized
in Table II.
As shown in Table II, the amount of catalyst had a modest influence
on the enantioselectivity and yield. Thus, the use of 50 mol% of cata-
lyst led to the expected product in high yield with ee of 35% (entry 3),
while the use of 30 mol% and 100 mol% of catalyst gave lower enan-
tioselectivity (entry 1, 22% ee; entry 2, 32% ee). Therefore, the optimal
amount of catalyst was 50 mol%. Moreover, the solvent also was found
to a important factor to this reaction. The yield and enantioselectivity in
polar solvent (THF, entry 4) were lower than those in less polar solvent
(
toluene, entry 6) or nonpolar solvent (n-hexane, entry 3). Although good
yield was obtained in CH2Cl2, the enantioselectivity was dramatically

Asymmetric Ring-Opening of Cyclohexene Oxide
1777
TABLE II Ring-Opening of Cylohexene Oxide Catalyzed by
(
−)-(S)-5/Ti(OPr-i)
4
2
5
Amount of
Catalyst
(mol%)
[α]
D
Temp.
(c 1,
Yield
◦
a
Entry
R
n
Solvent
( C) CH2Cl2) Products (%) e.e.%b e.e.%c
1
2
3
4
5
6
7
8
9
Me
Me
Me
Me
Me
Me
Me
Me
i-Pr
H
0
0
0
0
0
0
0
0
0
0
0
1
30
100
50
50
50
50
50
50
50
50
50
50
n-hexane
n-hexane
n-hexane
THF
CH2Cl2
toluene
toluene
toluene
toluene
toluene
toluene
toluene
0
0
0
0
0
+15
+22
+24
+19
+15
+27
+17
+22
+22
+28
+15
+13
66
6
6
6
6
6
6
6
7
30
55
45
27
45
45
50
35
48
53
57
46
22
32
35
28
22
40
25
30
41
32
22
43
0
25
−20
0
38
37
38
6
1
1
1
0
1
2
0
0
0
8
9
35
22
24
6
Cl
H
9
10
18
a
Isolated yield.
b
20
D
Determined by the comparison of sepecific rotation values: product 6, [α] + 42.7
6
20
D
(
9
4
c 0.75, CH2Cl2) with 62%ee ; product 8, [α] + 51.0 (c 1, CH2Cl2) with 63%ee; product
2
0
6
20
D
, [α] + 40.6 (c 1, CH2Cl2) with 59%ee ; product 10, [α] + 22.9 (c 1.2, CH2Cl2) with
D
9
2%ee.
cDetermined by HPLC with chiral column (Chiralcel OD).
◦
decreased (entry 5). The optimal reaction temperature was 0 C. The
enantioselectivity and yield were both decreased (entry 8) when the re-
action was carried out at lower temperature. At higher temperature,
although the yield was increased a little the enantioselectivity was de-
creased markedly (entry 7). The enantioselectivity was also influenced
by the nature of the ring-opening reagents. The enantioselectivities of
thiophenols (entry 6, 9–11) were higher than that of mercaptan (entry
1
2). Furthermore, better enantioselectivities were obtained when there
was electron-donating substituent in the benzene ring of thiophenols
(
entry 6, 9, 11).
The ring-opening products 6, 8–10 are known compounds, and by
comparison of the specific rotation value their absolute configuration
3
b
could be determined as 1S,2S according to the literature. As for
the unknown compound 7, we preliminarily determined its absolute

1
778
Z. Zhou et al.
TABLE III Experimental Data of Ring-Opening Products 6–10
◦
1H NMR
Products m.p. ( C)
Elemental Analysis (Calc./Found)
70.23/70.30 8.16/8.20
6
Thick
1.26 (m, 4H), 1.67 (m, 2H),
2
2
3
7
.10 (m, 2H), 2.34 (s, 3H),
.62 (m, 1H), 2.91 (s, 1H),
.28 (m, 1H), 7.14 (d, 2H),
.36 (d, 2H)
7
Thick
1.14–1.33 (m, 10H), 1.66 (m,
71.95/71.68 8.86/8.65
2
1
1
2
H), 2.07 (m, 2H), 2.50 (m,
H), 2.66 (m, 1H), 3.11 (s,
H), 3.27 (m, 1H), 7.16 (d,
H), 7.39 (d, 2H)
8
9
1
Thick
44–46
Thick
1.29 (m, 4H), 1.66 (m, 2H),
69.18/69.19 7.76/7.60
59.37/59.25 6.23/6.10
70.21/70.30 8.18/8.15
2
2
7
.06 (m, 2H), 2.74 (m, 1H),
.97 (s, 1H), 3.29 (m, 1H),
.24–7.47 (m, 5H)
1.26 (m, 4H), 1.66 (m, 2H),
2
2
7
.05 (m, 2H), 2.85 (m, 1H),
.99 (s, 1H), 3.26 (m, 1H),
.24 (d, 2H), 7.36 (d, 2H)
0
1.17 (m, 4H), 1.25 (m, 2H),
1
2
3
.99 (m, 2H), 2.14 (m, 1H),
.41 (s, 1H), 3.30 (m, 1H),
.80 (m, 2H), 7.27 (m, 5H)
configuration as 1S,2S by comparison of the specific rotation value with
the analogues. The experimental data of the products 6–10 are summa-
rized in Table III.
In conclusion, moderate enantioselectivity was obtained in the Schiff
base/Ti(OPr-i)4 catalyzed ring-opening reaction of epoxides with mer-
captan or thiophenols, which was consistent with the literature results.
Furthermore, better results were obtained using (−)-(S)-binaphthol as
the ligand. These studies will give helpful information to further de-
signing of ligands containing two hydroxy groups.
REFERENCES
[
1] D. M. Hodgson, A. R. Gibbs, and G. P. Lee, Tetrahedron, 52, 14361 (1996).
[
[
[
[
2] L. Z. Martinez, J. L. Leighton, D. H. Carsten, and E. N. Jacobsen, J. Am. Chem. Soc.,
117, 5897 (1995).
3] a) H. Yamashita and T. Mukaiyama, Chem. Lett., 1643 (1985); b) H. Yamashita, Bull.
Chem. Soc. Jpn., 61, 1213 (1988).
4] T. Iida, N. Yamamoto, H. Sasai, and M. Shibasaki, J. Am. Chem. Soc., 119, 4783
(
1997).
5] M. H. Wu and E. N. Jacobsen, J. Org. Chem., 63, 5252 (1998).

Asymmetric Ring-Opening of Cyclohexene Oxide
1779
[
[
[
[
6] J. Wu, X. L. Hou, L. X. Dai, L. J. Xia, and M. H. Tang, Tetrahedron: Asymmetry, 9,
431 (1998).
7] Z. H. Yang, L. X. Wang, Z. H. Zhou, Q. L. Zhou, and C. C. Tang, Tetrahedron: Asym-
metry, 12, 1579 (2001).
8] J. X. Cai, Z. H. Zhou, K. Y. Li, C. H. Yeung, and C. C. Tang, Phosphorus, Sulfur and
Silicon, 177, 189 (2002).
3
9] H. Adams, R. Bell, and Y. Y. Cheung, Y. Y. Tetrahedron: Asymmetry, 10, 4129 (1999).