One-step, enantiospecific transformation of cyclic, five-membered-1, 2-diols into their respective 1,2-bis(phenylsulfanyl) derivatives

Article abstract of DOI:10.1055/s-2003-41015

The enantiomeric cyclic, five-membered vic-diols reacted with (PhS) ₂/Bu₃P in benzene at 80 °C giving the corresponding bis(phenylsulfanyl) derivatives (42-74%) with complete inversion of configuration at both stereogenic centers. Si

Full text of DOI:10.1055/s-2003-41015

LETTER
1615
One-step, Enantiospecific Transformation of Cyclic, Five-membered-1,2-diols
into their Respective 1,2-Bis(phenylsulfanyl) Derivatives
E
J
nantiosp
a
ecific Trans
c
formation o
e
f
1,2-Diols
k
into 1,2-Bis(phen
S
ylsulfanyl)
D
e
k
rivatives arżewski,* Anil Gupta, Elżbieta Wojaczyńska, Renata Siedlecka
Institute of Organic Chemistry, Biochemistry and Biotechnology, Wrocław University of Technology, 50-370 Wrocław, Poland
Fax +48(71)3284064; E-mail: skarzewski@kchf.ch.pwr.wroc.pl
Received X July 2003
Abstract: The enantiomeric cyclic, five-membered vic-diols react-
ed with (PhS) /Bu P in benzene at 80 °C giving the corresponding
2
3
bis(phenylsulfanyl) derivatives (42–74%) with complete inversion
of configuration at both stereogenic centers. Similar reaction condi-
tions were also successfully used for the enantiospecific transfor-
mation of a single hydroxy group into the respective enantiomeric
thioether function. For other vic-diols the neighboring group partic-
ipation hampered the stereoselectivity of the double substitution.
Scheme 1
The primary alcohols reacted smoothly, whereas the sec-
Key words: diols, stereoselective synthesis, Mitsunobu reaction, ondary ones were much less reactive. To overcome this
thioethers
difficulty the use of high-pressure conditions was advo-
cated. Nonetheless, the application of this reaction to di-
6
ols has not been explored.
Chiral ligands with phosphorus-, nitrogen- and oxygen-
donating atoms play a key role in metal-catalyzed asym-
metric reactions. During the last decade, also sulfur-do-
nating chiral derivatives have appeared as promising
Thus, for the purpose of direct activation and substitution
of both hydroxy groups we devised and applied our ver-
sion of the Hata reaction, i.e. treatment of the diols with
diphenyl disulfide and tributylphosphine in THF or ben-
zene (toluene) solution under argon atmosphere in a
sealed tube at 80 °C. Additionally, monohydroxy ana-
logues of the diols were also tested in this reaction. Gen-
erally, the substitutions carried out in the aromatic solvent
required shorter reaction times and generated less side-
products (see below).
7
1
catalysts. In addition to more common heterodonating (P,
S) and (N, S) ligands, some interesting results have re-
cently been reported for (S, S)-donating chiral ligands.2
These findings have stimulated an increasing interest in
the synthesis of new chiral sulfur compounds suitable for
this purpose. Particularly, C -symmetric chiral 1,2-dithio-
2
ethers with a relatively rigid, cyclic structure are highly
3
Firstly, we applied the Hata reaction to the same type of
desirable chiral auxiliaries and ligands. However, there is
4
substrates as before and that process resulted in double
a rather limited number of available derivatives of this
2
a,e
substitution occurring with inversion of configuration at
both stereogenic centers. Thus, (1S,2S)-cyclopentanediol
type. Since chiral vic-diols are easily accessible, we
were interested in their transformation into the desired
chiral bis(phenylsulfanyl) derivatives. A classical proce-
dure consists in the conversion of a diol into dimesylate or
ditriflate followed by double nucleophilic substitution
with a thiolate anion. Because we had observed the insta-
bility of the intermediate vic-bis(sulfonate) esters we
turned our attention to the direct transformation method.
Previously, we had solved a similar problem by convert-
ing five-membered-ring vic-diols to the corresponding di-
(
1a) and its heterocyclic analogues 1b–d were trans-
formed into the corresponding (R,R)-bis(phenylsulfanyl)-
substituted products 2a–d18 in moderate to good yields.
(
Scheme 2; Table 1, entries 1–5). For the less effective re-
action run in THF, an increase of the reaction time to up
to 5 days led to the formation of elimination side-prod-
ucts. The antipode of 1c was converted to the respective
ent-2c. A complete stereospecifity of the reaction on ho-
mochiral substrates was confirmed by the absence (NMR,
GC) of any meso-disubstituted product. Moreover, if a
half of the usual amount of (PhS) /Bu P was used in the
4
azides using direct double Mitsunobu reaction.
Hata and others reported that diphenyl disulfide reduced
by tributylphosphine to the thiophosphonium salt reacts
easily with an alcohol. Thus the formed intermediate un-
dergoes nucleophilic substitution bringing about the de-
2
3
reaction with 1c, we obtained the mono-substituted, opti-
19
cally active cis-diastereomer 3 (46%) along with 2c
(
(
9%). Furthermore, (S)-1-benzyl-3-hydroxypyrrolidine
4) was easily converted into (R)-1-benzyl-3-phenylsulf-
sired conversion of alcohol into thiophenyl ether
5
(
Scheme 1).
anylpyrrolidine (5).
Additionally, we examined the reactions of 1c using in-
stead of (PhS) dimethyl, di(t-butyl) or di(2-naphthyl) di-
2
17
sulfide (C H , 72 h, 80 °C). Only in the case of (2-
6
6
Synlett 2003, No. 11, Print: 02 09 2003. Web: 13 08 2003.
Art Id.1437-2096,E;2003,0,11,1615,1618,ftx,en;G10303ST.pdf.
DOI: 10.1055/s-2003-41015
NaphthS) the enantiomeric bis-substituted derivative (+)-
2
(
3R,4R)-6 was obtained. In both earlier cases the reaction
©
Georg Thieme Verlag Stuttgart · New York

1
616
J. Skarżewski et al.
LETTER
Scheme 2
Scheme 3
Table 1 Enantiospecific Transformations of Hydroxyls to Phenyl-
sulfanyl Functions
Finally, we examined the use of the Hata reaction for the
transformation of acyclic diols. Interestingly, when the
classical method for transformation of cis-2-butene-1,4-
diol into the corresponding bis(phenylsulfanyl) derivative
2
0
20
Entry Diol/[a]D
Solvent/reaction
time (h)
Product/[a]D
Yield
(%)
(CH Cl )
2
2
[
i.e. its conversion to bis(tosylate) followed by the substi-
1
1a/+21
THF/72
2a/+29.7
42 (71)
11
tution with thiophenolate] was applied, we obtained the
mixture of cis- and trans-isomers (62% yield, 1:2.2 dr).
Thus, we used our Hata reaction conditions (C H , 72 h)
and these gave the desired cis-1,4-bis(phenylsulfanyl)-2-
butene in 92% yield (Scheme 4).
(
C H /22)
6 6
2
3
4
5
6
7
1b/a
C H + DMF/21
2b/+23.0
2c/+54.0
2d/+53.2
ent-2c/–54.0
3/+7.0
42
68
74
63
42
82
6
6
6
6
1c/+31.5
1d/+15
C H /21
12
6
6
C H /21
6
6
ent-1c/–31.5 C H /21
6
6
b
1c/+31.5
4/–3.7c
C H /72
6 6
C H /72
5/+21.1
6
6
a
b
c
For the preparation and properties of 1b, see ref.4,
A half of the usual amount of the reagents was used.
A commercial product from Aldrich, No. 36,694-3.
Scheme 4
failed and the expected thio-substituted products could However, when 1-phenyl-4-phenylsulfanylbutane-1,2-
not be detected. Thus the double substitution seems to be diol (100% de, R,R- 76% ee)13 was treated in the same
limited to the arylsulfanyl groups.
way, the isolated tris(phenylsulfanyl)-product (62%) con-
tained the mixture of isomers (36% de) only. (1S,2S)-1,2-
Diphenyl-1,2-ethanediol gave mainly meso-disubstituted
product14 (de 60%) along with the mostly racemized
trans-isomer. Both last results can be accounted for the
Then, we turned to the six-membered ring compounds and
(
S,S)-1,2-cyclohexanediol was treated with (PhS) /Bu P
2 3
in benzene at 80 °C for 21 hours and gave the mixture con-
taining 1,2-bis(phenylsulfanyl)cyclohexane (7, 42%
yield), the elimination side-products and butyl phenyl sul-
[
1,2]-PhS shift participation.10
fide. This reaction in THF did not work at all. The last Since the 1,3-phenylsulfanyl migration occurs rarely,
side-product resulted from the competitive nucleophilic we tried the direct substitution of the hydroxy group in
attack on the butyl group carbon atom of the oxophospho- (1S,3R)-1,3-diphenyl-1-hydroxy-3-phenylsulphanylpro-
nium salt. The obtained disubstituted product was mainly pane (9). This enantiomeric alcohol was successfully
8
15
trans-7 (83% de) but it contained also cis-meso-isomer obtained by deoxygenation of the respective diastereo-
(
by GC/MS). Moreover, the main product was consider- meric sulfoxide 8.1 In this case the Hata reaction went
6,20
ably racemized (22% ee by chiral HPLC). It seems that stereoselectively to the corresponding C -symmetric ho-
2
the process involves the formation of epoxides, which mochiral (1R,3R)-10 (Scheme 5).
have been postulated as a cause for the similar outcomes
of the double Mitsunobu reaction with trans-1,2-cyclo-
9
hexanediol. Another possibility comes from the forma-
tion of the cyclic phosphorus intermediate ester and S 1-
N
like mechanism. cis-1,2-Cyclohexanediol in the same re-
action gave also rac-trans-7 as the main product (62% de,
4
2% total). This result can be explained by S 1-like
N
Scheme 5
mechanism caused by the formation of the cyclic phenyl-
sulfonium ion ([1,2]-PhS shift participation)10
(
Scheme 3).
Synlett 2003, No. 11, 1615–1618 © Thieme Stuttgart · New York

LETTER
Enantiospecific Transformation of 1,2-Diols into 1,2-Bis(phenylsulfanyl) Derivatives
1617
Studies on the catalytic application of this and the previ-
ous cyclic homochiral bis-thioethers are underway.
NaOH, brine and dried over anhyd Na
evaporation, the crude product was purified by
chromatography on silica gel. Selected data for the obtained
SO . After
2 4
In conclusion, the developed stereospecific double substi-
tution on the five membered cyclic vic-diols offers simple
synthetic way to the corresponding enantiomeric bis(phe-
products are given below.
1
(18) (1R,2R)-2a: crystallizing oil. H NMR (CDCl ): d = 1.71–
3
1.77 (m, 2 H, CH ), 1.83–1.93 (m, 2 H, CH H ), 2.31–2.43
2
a
b
(
m, 2 H, CH H ), 3.58 (dd, 2 H, J = 5.3 Hz, J = 2.4 Hz,
a b 1 2
nylsulfanyl)-derivatives of C -symmetry, promising
2
1
3
CHS), 7.24 (s, 10 H, Ar). C NMR (CDCl ): d = 23.16,
3
chiral ligands for asymmetric synthesis.
3
3
1
2
1
0.94, 52.74, 126.72, 128.90, 131.26, 135.46. IR (film):
073, 3058, 3019, 3003, 2960, 2865, 1583, 1480, 1438,
–
1
091, 1025, 909, 736, 691 cm . MS (EI, 70 eV): m/z (%) =
Acknowledgment
+
+
+
86 (4.3) [M ], 177 (69) [M – PhS], 135(9) [PhSCH=CH ],
+
+
The authors thank the Polish Committee for Scientific Research for
financial support (KBN Grant 7 T09A 109 21).
09 (25) [PhS ], 67 (100) [C H ]. (3R,4R)-2b: mp 62–63 °C
5
7
1
(
MeOH). H NMR (CDCl ): d = 3.68 (dd, 2 H, J = 4.2 Hz,
3
1
J = 3.0 Hz, CHS), 3.83 (dd, 2 H, J = 9.6 Hz, J = 3.0 Hz,
2
1
2
CH H ), 4.34 (dd, J = 9.5 Hz, J = 5.4 Hz, CH H ), 7.24 (s,
a
b
1
2
a
b
References
13
1
1
1
0 H, Ar). C NMR (CDCl ): d = 52.14, 72.25, 127.37,
3
29.15, 131.67, 134.05. IR (KBr): 3049, 2952, 2926, 2873,
(1) Bayón, J. C.; Claver, C.; Masdeu-Bultó, A. M. Coord. Chem.
Rev. 1999, 193–195, 73.
–
1
580, 1482, 1469, 1438, 1065, 894, 749, 697, 689 cm . MS
+
+
(
EI, 70 eV): m/z (%) = 288 (4) [M ], 179 (40) [M – PhS],
(2) (a) Dieguez, M.; Ruiz, A.; Claver, C.; Pereira, M. M.;
Gonsalves, A. M. D. R. J. Chem. Soc., Dalton Trans. 1998,
+
+
135(23) [PhSCH=CH ], 109 (68) [PhS ], 69 (100)
+
[
C H O ]. (+)-(3R,4R)-2c: from (+)-(3S,4S)-1c: mp 58–59
3517. (b) Dieguez, M.; Ruiz, A.; Claver, C.; Pereira, M. M.;
4 5
2
0
2a
°C. [a]D +54.0 (c 1.00, CH Cl , >98% ee), {Lit. (+)-
Flor, M. T.; Bayón, J. C.; Serra, M. E. S.; Gonsalves, A. M.
D. R. Inorg. Chim. Acta 1999, 295, 64. (c) Dieguez, M.;
Ruiz, A.; Masdeu-Bultó, A. M.; Claver, C. J. Chem. Soc.,
Dalton Trans. 2000, 4154. (d) Jansat, S.; Gómez, M.;
Muller, G.; Dieguez, M.; Aghmiz, A.; Claver, C.; Masdeu-
Bultó, A. M.; Flores-Santos, L.; Martin, E.; Maestro, M. A.;
Mahia, J. Tetrahedron: Asymmetry 2001, 12, 1469.
2 2
2
0
(
3R,4R)-2c: [a]D +52.7 (c 0.55, CHCl )}. UV/Vis
3
(
(
7
CH CN): l (log e) = 216 nm (3.84), 256 nm (3.67). CD
3
max
CH CN): l (De) = 229 (–1.4), 243(0), 258 (+1.1). MS (EI,
3
+
+
0 eV): m/z (%) = 377 (2) [M ], 268 (75) [M – PhS], 149
+
+
(100) [PhSCH=CH-CH ],116 (11) [C H NS ], 91 (51)
2 5 10
+
20
[
C H ]. (–)-(3S,4S)-2c: mp 58–59 °C. [a] –54.0 (c 1.16,
7
7
D
1
CH Cl ). (3R,4R)-2d: mp 49–51 °C (MeOH). H NMR
(
e) Flores-Santos, L.; Martin, E.; Dieguez, M.; Masdeu-
2
2
(
(
(
CDCl ): d = 0.87 (t, 3 H, CH ), 1.25 (m, 18 H, CH ), 1.55
Bultó, A. M.; Claver, C. Tetrahedron: Asymmetry 2001, 12,
3
3
2
m, 2 H, CH ), 2.41 (m, 2 H, CH ), 2.68 (m, 2 H, CH ), 3.24
3029. (f) Bastero, A.; Claver, C.; Ruiz, A. Catal. Lett. 2002,
2
2
2
m, 2 H, CH ), 3.63 (t, 2 H, NCH ), 7.24–7.40 (m, 10 H,
82, 85.
2
2
1
3
ArH). C NMR (CDCl ): d = 14.11, 22.68, 24.21, 27.30,
(
(
3) Whitesell, J. K. Chem. Rev. 1989, 89, 1581.
3
2
5
3
9.33, 29.39, 29.52, 29.57, 29.62, 30.19, 31.90, 51.05,
4) Skarżewski, J.; Gupta, A. Tetrahedron: Asymmetry 1997, 8,
6.53, 59.18, 127.26, 129.11, 131.54, 134.45. IR (KBr):
1861.
–
1
058, 2925, 2853, 1584, 1480, 738, 690 cm . MS (EI, 70
(
5) (a) Hata, T.; Sekine, M. Chem. Lett. 1974, 15, 837.
+
eV): m/z (%) = 149 (100) [PhSCH=CH-CH ], 116(13)
[
(
(
b) Nakagawa, I.; Hata, T. Tetrahedron Lett. 1975, 1409.
c) Nakagawa, I.; Aki, K.; Hata, T. J. Chem. Soc., Perkin
2
+
+
C H NS ], 82(42) [C H N ]. (3R,4R)-6: Obtained by the
5 10 5 8
usual procedure using: (+)-(3S,4S)-1c (1 equiv), (2-
Trans. 1 1983, 1315. (d) For a review, see: Valentine, D. H.;
Hillhouse, J. H. Synthesis 2003, 317.
NaphthS) (3 equiv) and Bu P (4 equiv) in dry benzene.
2
3
Yield 88%. Mp 98–100 °C (CH Cl –hexane). R = 0.45 (n-
(
6) Kotsuki, H.; Matsumoto, K.; Nishizawa, H. Tetrahedron
Lett. 1991, 32, 4155.
2
2
f
2
0
1
hexane/EtOAC 9:1): [a]D +108.2 (c 0.78, CH Cl ). H
2
2
NMR (CDCl ): d = 2.73 (dd, 2 H, J = 10.3 Hz, J = 3.9 Hz),
(
(
7) Siedlecka, R.; Skarżewski, J. Synlett 1996, 757.
8) Zyk, N. V.; Beloglazkina, E. K.; Sosnyuk, S. E.; Bulanov,
M. N.; Chudinov Yu, B. Izv. Akad. Nauk, Ser. Khim. 2000,
3
1
2
3
.21–3.31 (m, 2 H), 3.65 and 3.79 (q, 2 H, J = 13.7 Hz,,
AB
AB-system, CH Ph), 3.79–3.83 (m, 2 H), 6.98–7.74 (m, 19
2
1
3
H, ArH). C NMR (CDCl ): d = 52.57, 59.69, 59.98, 126.42,
1569.
3
1
1
3
26.87, 127.50, 127.71, 128.05, 128.74, 128.84, 128.96,
(
9) Göksu, S.; Seçen, H.; Sűtbeyaz, Y. Synthesis 2002, 2373.
29.15, 130.29, 132.53, 132.86, 133.98, 138.82. IR (KBr):
(
10) For a review, see: Fox, D. J.; House, D.; Warren, S. Angew.
–
1
050, 2961, 1727, 1271, 1130, 819, 740 cm . MS (EES, 4.5
Chem. Int. Ed. 2002, 41, 2462.
+
kV): m/z = 478.7 [M + H] .
(11) Hudson, R. F.; Withey, R. J. J. Chem. Soc. B 1966, 237.
(12) Martin, E.; Tovilla, J.; Torrens, H. Synthesis 2000, 1109.
(13) Skarżewski, J.; Wojaczńska, E.; Turowska-Tyrk, I.
Tetrahedron: Asymmetry 2002, 13, 369.
(
19) (3S,4R)-3: Obtained by the usual procedure using: (+)-
(
3S,4S)-1c (1 equiv), PhSSPh (1.5 equiv) and Bu P (2 equiv)
3
1
in dry benzene. Mp 66–67 °C (EtOH). H NMR (CDCl ):
3
d = 2.15–2.62 (m, 2 H, CH ), 2.82 (br s, 1 H, OH), 3.05–3.11
(
14) (a) Yoshimura, N.; Igarashi, K.; Funasaka, S.; Mukaiyama,
T. Chem. Lett. 2001, 640. (b) We confirmed the structure of
meso-1,2-diphenyl-1,2-di(phenylsulphanyl)ethane, mp 195–
2
(
m, 2 H, CH ), 3.66 (s, 2 H, CH ), 3.77 (m, 1 H, CH-S), 4.30–
2
2
4
.32 (m, 1 H, CH-O), 7.19–7.37 (m, 10 H, ArH), cis-vic-
3
methine hydrogens coupling: J = 5.9 Hz (decoupling
experiment). C NMR (CDCl ): d = 52.51, 58.18, 60.56,
196 °C by the preliminary results of X-ray analysis.
1
3
(
(
15) Balicki, R. Synthesis 1991, 155.
3
6
1
2
1.76, 70.71, 127.21, 127.64, 128.78, 129.20, 129.52,
30.56, 135.63, 138.60. IR (film): 3403, 3060, 3028, 2935,
802, 1584, 1481, 1438, 1143, 1090, 1026, 740, 700 cm .
16) Skarżewski J., Siedlecka R., Wojaczyńska E., Zielińska-
Błajet M.; Tetrahedron: Asymmetry; 2002, 13: 2105.
17) General Procedure for the Preparation of Bis(sulfides):
A solution of diol (0.8 mmol), PhSSPh (1.05g, 4.8 mmol)
–
1
(
1
(
R)-5: oil. R = 0.27 (n-hexane/EtOAc 9:1). H NMR
f
(
2
CDCl ): d = 1.74–1.78 (m, 1 H, H ), 2.25–2.29 (m, 1 H, H ),
and Bu P (1.59 mL, 6.4 mmol) in dry benzene (5 mL) was
placed under argon in a reaction ampule. The sealed tube
was heated at 80 °C for three days. Thereafter the cooled
3
4
4
3
.40 (dd, 1 H, J = 9.9 Hz, J = 6.2 Hz, H ), 2.51–2.55 (m, 1
1 2 2
H, H ), 2.61–2.65 (m, 1 H, H ), 3.01 (dd, 1 H, J = 9.9 Hz,
5
5
1
J = 7.3 Hz, H ), 3.53 and 3.60 (q, 2 H, J = 12.9 Hz, AB-
mixture was diluted with Et O (20 mL), washed with 2 M
2
2
AB
2
Synlett 2003, No. 11, 1615–1618 © Thieme Stuttgart · New York

1
618
J. Skarżewski et al.
LETTER
16
system, CH Ph), 3.67–3.72 (m, 1 H, H ), 7.07–7.27 (m, 10
(20) (1S,3R,S )-8 was deoxygenated15 to (1S,3R)-9 in 71%
2
3
S
H, ArH). 13C NMR (CDCl ): d = 32.78, 43.47, 53.64, 60.54,
yield. R = 0.64 (t-BuOMe/CHCl /n-hexane, 2.5:2:7). [a]
20
3
f
3
1
D
6
1
1
1.22, 126.49, 127.44, 128.70, 129.17, 129.28, 130.07,
+127.1 (1.88, CH Cl , >95% ee). H NMR (CDCl ): d = 1.85
2 2 3
37.12, 139.17. IR(film): 3059, 2959, 2792, 1584, 1480,
(d, 1 H, -OH, J = 3.5 Hz), 2.13–2.19 (m, 1 H, CH ), 2.35–
2
–
1
439, 1145, 1026, 738, 699 cm . (+)-(1R,3R)-10: oil.
2.41 (m, 1 H, CH ), 4.35 (dd, 1 H, CH-S, J = 9.8 Hz,
2
1
2
0
R = 0.58 (n-hexane/EtOAc 10:1). Yield 65%. [a]
+150.0
J = 5.6 Hz), 4.48 (dt, 1 H, CH-O, J = 9.5 Hz, J = 3.6 Hz),
f
D
2
1
2
1
13
(
c 2.34, CH Cl , >95% ee). H NMR (CDCl ): d = 2.53 (t, 2
6.91–7.23 (m, 15 H, ArH). C NMR (CDCl ): d = 45.47,
50.55, 72.46, 126.13, 127.58, 127.73, 128.16, 128.39,
128.92, 128.96, 129.11, 132.86, 134.89, 141.77, 144.65.
2
2
3
3
H, J = 7.6 Hz, CH ), 4.01 (t, 2 H, J = 7.6 Hz, CH), 7.07–7.27
2
3
1
(
1
1
m, 20 H, ArH). C NMR (CDCl ): d = 41.95, 50.72,
3
27.58, 127.94, 128.44, 128.95, 129.09, 132.74, 134.81,
40.71.
Synlett 2003, No. 11, 1615–1618 © Thieme Stuttgart · New York