Regio- and stereoselective ring-opening of epoxides using organic dithiophosphorus acids as nucleophiles

Article abstract of DOI:10.1016/S0040-4039(02)01715-X

A practical method for the synthesis of β-hydroxymercaptans has been successfully developed through the ring-opening of epoxides with organic dithiophosphorus acids 1. Highly regio- and stereoselective products, β-hydroxyalkyl dithiophosphates, which were transformed to the corresponding synthetically valuable β-hydroxymercaptans by further reduction, were obtained under mild reaction conditions without any catalyst or promoter. Highly enantioselective ring-opening reaction of cyclohexene epoxide with 1 was realized in the presence of a chiral (salen)Ti(IV) complex.

Full text of DOI:10.1016/S0040-4039(02)01715-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7609–7611
Regio- and stereoselective ring-opening of epoxides using organic
dithiophosphorus acids as nucleophiles
Zhaoming Li, Zhenghong Zhou, Kangying Li, Lixin Wang, Qilin Zhou and Chuchi Tang*
State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University,
Tianjin 300071, PR China
Received 28 March 2002; revised 9 August 2002; accepted 16 August 2002
Abstract—A practical method for the synthesis of b-hydroxymercaptans has been successfully developed through the ring-opening
of epoxides with organic dithiophosphorus acids 1. Highly regio- and stereoselective products, b-hydroxyalkyl dithiophosphates,
which were transformed to the corresponding synthetically valuable b-hydroxymercaptans by further reduction, were obtained
under mild reaction conditions without any catalyst or promoter. Highly enantioselective ring-opening reaction of cyclohexene
epoxide with 1 was realized in the presence of a chiral (salen)Ti(IV) complex. © 2002 Elsevier Science Ltd. All rights reserved.
The stereoselective ring-opening of meso-epoxides with
various nucleophiles 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 cen-
ters. A wide variety of nucleophiles are used in the
aforementioned ring-opening reaction.1 Among them,
sulfur nucleophiles are important and lead to the for-
mation of synthetically valuable b-hydroxymercaptans
or b-hydroxysulfides. The typically used sulfur nucle-
ophiles are alkane- and arene-thiols.1–8 This ring-open-
ing reaction is generally carried out in the presence of a
catalyst or promoter such as Ti(OPr-i )4,2 metal(II)
silicon–sulfur reagents, such as i-Pr3SiSH in the pres-
ence of DBU,10 Me3SiNCS, Me3SiOCSMe and
Me3SiSPh in the presence of Bu4NF11 are regioselective
ring-opening nuleophiles which lead to the correspond-
ing b-hydroxysulfides.
Early in 1965, Pudovik reported the reaction of dithio-
phosphorus acids with a-substituted epoxides.12 How-
ever, there has been no any further investigation into
this reaction during the past three decades. Recently,
we discovered that when dithiophosphorus acids were
used as the nucleophiles, this ring-opening reaction
could occur not only regioselectively, but also enan-
tioselectively. Additionally, the following features are
also worth noting. (1) Mild reaction conditions without
any catalyst or promoter. (2) The reagents are readily
available. (3) The resulting products can be trans-
formed further into synthetically valuable b-hydroxy-
mercaptan intermediates 3 through reduction. There-
fore, this work affords a convenient and practical
method for the synthesis of b-hydroxymercaptans, espe-
cially the synthesis of optically active b-hydroxymer-
captans (Scheme 1).
D
-tartrates,3 quaternary ammonium salts,4 polyethylene
glycol 4000,5 Ga/Li bis(binaphthoxide) complex6 and
metal salen complexes,7,8 etc. The resulting products,
b-hydroxysulfides, can be obtained with high regio- and
stereoselectivity. In addition, some other sulfur nucle-
ophiles containing silicon have also been described. For
example, the ring opening reaction with Ph3SiSH, the
mono protected form of H2S, takes place with high
regioselectivity in the presence of the Et3N/MeOH sys-
tem to give b-hydroxymercaptans in good yields.9 Other
Scheme 1.
* Corresponding author. Fax: +86 22 23503438; e-mail: c.c.tang@eyou.com
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01715-X

7610
Z. Li et al. / Tetrahedron Letters 43 (2002) 7609–7611
Table 3. Analytical data for compounds 6
Phosphorus–sulfur reagent 1 reacted with meso-epox-
ides 4 at 0°C for 0.5 h in toluene to form compounds 2
in excellent yields (Table 1) whose structures were
6
X
n2D0
Yield (%)
31P NMR (l, ppm)
1
confirmed by 31P NMR, H NMR and elemental analy-
a
b
c
d
e
H
Me
Et
1.5244
1.5204
1.5138
1.5706
92
88
95
93
94
95.14
95.60
96.48
92.21
95.29
ses. The reaction was found to be completely stereose-
lective and the trans products were obtained.
Compounds 2 were directly reduced with LiAlH4 to
give b-hydroxymercaptans 3 in 54–63% yields (Table
2).13
Ph
PhCH2O 1.5564
Similarly, the reactions of the phosphorus–sulfur
reagent 1b with mono-substituted epoxides 5 operated
under the same conditions to form the ring-opened
products 6, highly regioselectively, in excellent yields
(Table 3). Compounds 6 can also be transformed into
the corresponding b-hydroxymercaptans through
reduction (Table 2).13 In each case, the nucleophilic
ring-opening occurred on the less hindered carbon of
the epoxides (Scheme 2). The structures of compounds
6 were confirmed by 31P NMR, 1H NMR and elemental
analyses.
Scheme 2.
Scheme 3.
The reaction of 1b with (+)-(R)-styrene oxide14 was also
studied. The reaction was found to be highly regioselec-
tive and stereospecific. The corresponding (+)-(R)-7 was
obtained in 91% yield and in 88% ee (Scheme 3).15
Tang7 firstly reported the enantioselective ring-opening
reaction of meso-epoxides with various thiols catalyzed
by a chiral (salen)Ti(IV) complex formed in situ from
salen 8 and Ti(OPr-i )4. The highest ee value obtained
was 63%. We applied this catalytic system to the ring-
opening reaction of cyclohexene epoxide with 1b. The
corresponding ring-opened product 9 was obtained in
94% yield and in 73% ee (Scheme 4).16 Thioester 9 was
further reduced to give (+)-(S,S)-2-mercaptocyclohex-
anol in 57% yield and 74% ee, [h]D +29.0 (c 2,
CHCl3).17
Table 1. Analytical data for compounds 2
2
R
n
n2D0
Yield (%)
31P NMR (l, ppm)
a
b
c
d
e
f
g
h
i
MeO
EtO
PrO
BuO
Et
Ph
EtO
Ph
2
2
2
2
2
2
1
1
4
4
1.5432
1.5262
1.5164
1.5144
1.5513
Thick
1.5268
Thick
1.5120
Thick
90
95
93
87
90
92
93
95
88
91
99.24
94.18
94.60
94.57
81.86
64.18
93.70
62.87
94.96
65.15
In conclusion, we have succeeded in developing a highly
regio- and stereoselective ring-opening reaction of
epoxides with the phosphorus–sulfur reagents 1. Fur-
thermore, an enantioselective ring-opening reaction was
accomplished with an ee value of 73% in the presence
EtO
Ph
j
Table 2. Reduction of different thiophosphorus esters 2 and 6

Z. Li et al. / Tetrahedron Letters 43 (2002) 7609–7611
7611
Scheme 4.
of a chiral (salen)Ti(IV) complex. Reduction of the
ring-opened product gave the corresponding b-hydroxy-
mercaptan in good yield. Therefore, this method is very
useful in organic synthesis, especially in multifunctional
natural product synthesis.
11. Tanabe, Y.; Mori, M.; Yoshida, Y. J. Chem. Soc., Perkin
Trans. 1 1997, 671.
12. Pudovik, A. N.; Faezurrin, E. M.; Zhuravrev, G. E. Zh.
Obshch. Khim. 1965, 36, 718.
13. For 2-mercaptocyclohexanol: pale yellow liquid (stench),
1H NMR (CDCl3, l): 3.10 (m, 1H, CHOH), 3.05 (s, 1H,
OH), 2.46 (m, 1H, CHSH), 1.99 (m, 2H, CH2), 1.69 (m,
2H, CH2), 1.49 (d, 1H, J=8.5 Hz, SH), 1.29 (m, 4H,
CH2). M+: 132 (see Ref. 17). For 2-mercaptocyclooctanol:
pale yellow liquid (stench), 1H NMR (CDCl3, l): 3.44
(m, 1H, CHOH), 2.91 (s, 1H, OH), 2.85 (m, 1H, CHSH),
1.59 (d, 1H, J=8.6 Hz, SH), 1.29 (m, 12H, CH2). Ele-
mental analysis: Found: C, 59.80; H, 10.05. Calcd for
C8H16OS: C, 59.95; H, 10.06. For 1-mercapto-2-butanol:
pale yellow liquid (stench), 1H NMR (CDCl3, l): 3.60
(br, 1H, OH), 2.45 (m, 1H, CHOH), 2.38 (m, 2H,
CH2SH), 1.52 (m, 2H, CH2), 1.34 (t, 1H, SH), 0.95 (t,
3H, J=4.5 Hz, CH3).
Acknowledgements
We are grateful to the National Natural Science Foun-
dation of China (No. 29872016 and 20002002) for
generous financial support.
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