The deoxygenation of sulfoxide mediated by the Ph3P/Lewis acid combination and the application to the kinetic resolution of racemic phosphines using optically active sulfoxide

Article abstract of DOI:10.1016/j.tet.2005.01.127

It was found that the combination of Ph₃P/TiCl₄ was an effective promoter for the deoxygenation of sulfoxides and gave the corresponding sulfides in good yield (up to 97%) under mild conditions. This method was applied to the reaction between racemic phosphines and (R)-methyl p-tolyl sulfoxide, and it was found that the kinetic resolution was achieved in moderate selectivities.

Full text of DOI:10.1016/j.tet.2005.01.127

Tetrahedron 61 (2005) 3587–3591
The deoxygenation of sulfoxide mediated by the Ph P/Lewis acid
3
combination and the application to the kinetic resolution of
racemic phosphines using optically active sulfoxide
*
Satoshi Kikuchi, Hiroyuki Konishi and Yukihiko Hashimoto
Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
Received 13 December 2004; accepted 24 January 2005
3 4
Abstract—It was found that the combination of Ph P/TiCl was an effective promoter for the deoxygenation of sulfoxides and gave the
corresponding sulfides in good yield (up to 97%) under mild conditions. This method was applied to the reaction between racemic phosphines
and (R)-methyl p-tolyl sulfoxide, and it was found that the kinetic resolution was achieved in moderate selectivities.
q 2005 Elsevier Ltd. All rights reserved.
5
a
1
. Introduction
proceeded in good yield under mild conditions, and the
reduction of 1,2-dicarbonyl compounds was smoothly
5
e
Sulfinyl group is one of the most important functional
groups in organic synthesis and there are many reports of
stereoselective reactions using sulfinyl group as a chiral
mediated by the Ph P/AlBr combination. We herein
3 3
would like to describe the deoxygenation of sulfoxides
mediated by the phosphine and Lewis acid combination
under mild conditions. Moreover, we would like to show the
application to the kinetic resolution of racemic phosphines.
1
auxiliary with high stereoselectivity. The sulfinyl group is
usually eliminated in two steps; first, the sulfoxide
is deoxygenated to sulfide, and after that, the sulfide is
removed by catalytic hydrogenation or other chemical
2
means. So, until now, many kinds of methods of the
2. Results and discussion
deoxygenation of sulfoxides have been developed; using
metal hydride reagents (LiAlH , NaBH , etc.), low-valent
metallic species (SnCl , VCl , TiCl etc.), halide ions (HI,
4
4
2.1. The deoxygenation of sulfoxide
2
2
3
3
,4
TMSI, TiI etc.) and so on. And phosphines were also
4
known as reductants for sulfoxides.
deoxygenation of diphenyl sulfoxide was mediated by Ph P,
4
a,b
First, we examined the deoxygenation of diphenyl sulfoxide
1a) using the combination of Ph P and several Lewis acids,
such as AlCl , BF $OEt , SnCl and TiCl , in CH Cl at
room temperature. Among Lewis acids examined, it was
found that only TiCl gave a good result. However, under
these conditions, the deoxygenation of other aliphatic
sulfoxides could not proceed in satisfied yield. So, we
examined the effect of solvents in the deoxygenation of
dibenzyl sulfoxide (1b) using Ph P and TiCl combination.
For example, the
(
3
3
in the presence of BF $OEt , under acetic acid reflux
3
3
3
2
4
4
2
2
2
condition. However, in these cases, the drastic conditions
were required and the ranges of substrates were limited.
Therefore, it was desired the development of the deoxy-
genations using phosphines, which proceeded under mild
conditions and had high generalities of substrates.
4
3
4
Then, it was found that THF was the most effectively
solvent and the highest yield (96%) was achieved.
On the other hand, we have recently investigated the
reaction mediated by the combination of phosphine and
Lewis acid and it has been already reported that the several
reactions proceeded in good yield with high stereo-
selectivity using this combination. For example, the
reduction of various a-bromocarboxylic acid derivatives
Under the optimized conditions, the deoxygenation of
several kinds of sulfoxides was carried out. The results are
summarized in Table 1.
5
,6
As can be seen from Table 1, it was found that the
deoxygenation of sulfoxides was effectively mediated by
this combination. Moreover, it should be noted that even if
Keywords: Phosphine; Lewis acid; Deoxygenation; Kinetic resolution.
*
Corresponding author. Tel.: C81 3 5841 7269; fax: C81 3 5841 7281;
e-mail: hashimoto@chiral.t.u-tokyo.ac.jp
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.01.127

3
588
S. Kikuchi et al. / Tetrahedron 61 (2005) 3587–3591
P/TiCl
Table 1. The deoxygenation of sulfoxides using the combination of Ph
3
4
a
Entry
1
Substrate
Time (h)
24
Yield (%)
1a
88
2
3
1b
1c
2
96
b
88
24
4
5
6
1
92
78
67
1d
1e
24
2
7
8
1f
14
96
1g
1h
2
97
90
c
9
14
a
Isolated yields.
Reaction was carried out using 0.5 equiv of TiCl .
4
Reaction was carried out at 60 8C
b
c
the substrates possessed the bulky substituents, namely
secondary or tertiary alkyl sulfoxides, the reaction pro-
ceeded smoothly in good yield (entries 5, 7, 9). And the
reaction was also found to proceed in 88% yield using a
reported using selenoxide having an optically active
8
binaphthyl skeleton. But there were few reports to obtain
the optically active phosphines using such a kinetic
resolution. Then, we examined the kinetic resolution of
racemic phosphines using optically active sulfoxides and
Lewis acid combinations.
catalytic amount of TiCl (0.5 equiv) although the reaction
4
rate was slower than that of the reaction using excess TiCl4
(
entries 2 and 3).
Initially, we carried out the kinetic resolution of racemic
methyl(1-naphthyl)phenylphosphine using the combination
of (R)-methyl p-tolyl sulfoxide (2a) and TiCl in THF.
In summary, we found that the deoxygenation of sulfoxides
smoothly proceeded in the presence of the Ph P and TiCl
combination in THF at room temperature and that this
deoxygenation had high generalities.
3
4
4
Then, the reaction was found to proceed smoothly to give
(
S)-methyl(1-naphthyl)phenylphosphine in 32% yield with
8% ee.
1
2
.2. Kinetic resolution of racemic phosphines
Next, we screened a variety of optically active sulfoxides
Fig. 1) and TiCl combination in the kinetic resolution of
(
It is possible to consider this reaction, deoxygenation of
sulfoxides, as the oxidation of the phosphine using the
sulfoxide and Lewis acid combination. So, if the optically
active sulfoxide is used with Lewis acid, it is assumed that
this reaction can be applied to the asymmetric oxidation.
Namely, it is expected that the kinetic resolution of racemic
phosphines can be achieved to give the optically active
phosphines. The optically active phosphines have many
important roles in organic syntheses, especially in the
4
racemic methyl(1-naphthyl)phenylphosphine. Among the
sulfoxides examined (2a–e), it was found that the highest
enantioselectivity was achieved in the case of using (R)-
methyl p-tolyl sulfoxide (2a). So, under these conditions,
kinetic resolution of several sorts of racemic phosphines
(3a–e) was carried out. The results are summarized in
Table 2.
7
transition metal catalyzed asymmetric reactions. There-
As shown in Table 2, the moderate enantioselectivity could
be achieved in the reaction of P-chiral phosphine derivatives
(3a, 3b), the planer chiral phosphine (3d) and even the
phosphine having a chiral center on neighboring carbon
fore, a lot of methods for preparation of optically active
phosphines have been developed. Recently, the kinetic
resolution of planar chiral ferrocenyl phosphine was

S. Kikuchi et al. / Tetrahedron 61 (2005) 3587–3591
3589
atom (3c). Among them, it was noticed that the better results
were obtained in the reaction of phosphines possessing the
coordinating group (3b, 3d).
2.3. Mechanism
The mechanism of the kinetic resolution of methyl-
1-naphthyl)phenylphosphine (3a) could be explained as
follows (Scheme 1): first, TiCl coordinated the oxygen
(
4
atom of (R)-methyl p-tolyl sulfoxide (2a). After that,
phosphine (3a) attacked sulfur atom from behind the lone
pair and then the intermediate (4a) and (4b) were formed.
However, the formation of the intermediate (4b) was more
disadvantageous than the formation of the intermediate (4a)
because of the steric repulsion between naphthyl substituent
and p-tolyl substituent. So, the reaction prefers to go
through the intermediate (4a) to give the intermediate (5)
and the (S)-methyl(1-naphthyl)phenylphosphine oxide was
formed preferably.
Figure 1. The used sulfoxide and the enantiomeric excess of methyl(1-
naphthyl)phenylphosphine resolved by the sulfoxide.
3. Conclusion
We found that the deoxygenation of many kinds of
sulfoxides was effectively promoted by the combination of
Table 2. The kinetic resolution of several racemic phosphines mediated by the combination of (R)-methyl p-tolyl sulfoxide and TiCl
4
a
Entry
Substrate
Temperature (8C)
Phosphine
ee (%)
b
Yield (%)
Ref.
18b
c,d
18 (S)
1
3a
K40
32
e
2
3
4
3b
3c
3d
0
0
0
37
21
34
23 (S)
19
20
21
f
12 (S)
f
26 (R)
f
5
3e
rt
49
4 (S)
22a
a
These were the lowest temperatures to be able to carry out the reaction.
Isolated yields.
Determined by chiral HPLC analysis (Daicel Chiralcel OJ).
The corresponding phosphine oxide was obtained in 59% yield with 14% (S) ee.
Determined by chiral HPLC analysis (Daicel Chiralcel OJ) of the corresponding phosphine–borane.
Determined by optical rotation.
b
c
d
e
f

3590
S. Kikuchi et al. / Tetrahedron 61 (2005) 3587–3591
argon atmosphere. The reaction was quenched with
saturated sodium hydrogencarbonate (10 mL), and the
mixture was extracted with ether (3!10 mL). The com-
bined ether layers were washed with brine (1!10 mL) and
dried over Na SO . This organic layer was filtered and
2
4
evaporated under reduced pressure, and then the crude
product was purified by preparative TLC to give the
corresponding sulfide. All sulfides are known compounds
and were characterized by a comparison of their spectral
data with those of authentic samples prepared or those from
9
–11,23,24
the literature (Table 1).
4
.3. General procedure for kinetic resolution
To a solution of (R)-methyl p-tolyl sulfoxide (0.12 mmol)
and TiCl (0.15 mmol) in THF (2 mL) was added a solution
4
of racemic phosphine (0.2 mmol) in THF (1 mL) and the
mixture was stirred at appropriate temperature under an
argon atmosphere. The reaction was quenched with aqueous
1
CH Cl (3!10 mL). The combined organic layers were
N NaOH (10 mL) and the mixture was extracted with
2
2
dried over Na SO . This organic layer was filtered and
2
4
evaporated under reduced pressure, and then the crude
product was purified by preparative TLC to give the desired
chiral phosphines. Absolute configurations and enantio-
meric excess of all products were determined by a
comparison of their optical rotation or HPLC analysis
Scheme 1.
Ph P and TiCl under mild conditions in good yield. This
3
4
reaction was found to be a very useful reaction in organic
synthesis because of the easy operation, mild conditions and
high generalities of substrates. Moreover, it was found that
1
8b–22a
with those of the literature (Table 2).
4
.3.1. (S)-Methyl(1-naphthyl)phenylphosphine (3a). The
the (R)-methyl p-tolyl sulfoxide/TiCl combination was the
4
enantiomeric excess was determined as 18% by an HPLC
analysis using chiral column: Daicel Chiralcel OJ, hexane:
2-propanolZ93:7, 0.6 mL/min, 10.3 min (R), 13.9 min (S).
The absolute configuration was determined as S by a
effective promoter for the kinetic resolution of several types
of racemic phosphines. Further examination of the kinetic
resolution is now in progress.
comparison of their optical rotation with that of the
literature.
2
5
4. Experimental
1
8b
4
.3.2. (S)-Methyl(1-naphthyl)phenylphosphine oxide.
4
.1. General
The enantiomeric excess and absolute configuration were
determined as 14% (S) by an HPLC analysis using chiral
column: Daicel Chiralcel OJ, hexane:2-propanolZ90:10,
The starting materials (1a, 1b, 1e) and reagents, purchased
from commercial suppliers, were used after standard
purification. Solvents were dried over sodium or molecular
sieves, and were distilled before use. The reaction flasks
0
.6 mL/min, 19.4 min (S), 24.0 min (R).
4
.3.3. (S)-2-Methoxyphenyl(methyl)phenylphosphine
were flame-dried under a steam of argon. Preparative TLC
(
1
PTLC) was carried out with Wakogel B-5F. H NMR
(3b). The enantiomeric excess and absolute configuration
were determined as 23% (S) by an HPLC analysis of the
corresponding phoshphine–borane using chiral column:
Daicel Chiralcel OJ, hexane:2-propanolZ90:10, 0.5 mL/
spectra were recorded on a Varian Mercury 300 at 300 MHz
using tetramethylsilane as an internal standard. Optical
rotations were recorded on a JASCO DIP-360. Analytical
HPLC was performed using a Daicel Chiralcel OJ column
1
8b
min, 17.2 min (S), 32.9 min (R).
9
with the detector wavelength at 254 nm. Sulfoxides (1c,
1
10
11
12
13
4
(
.3.4. (S)-(2-Methoxy-1-methylethyl)diphenylphosphine
3c). The enantiomeric excess was determined as 12% by an
d, 1f, 151g, 1h ), enantiomerically pure sulfoxides
2a, 2b, 2c, 2d, 2e ) and phosphines (3a, 3b,
3
procedures. TiCl was used as a 3 mol/L solution in hexane.
14 13 16 17 18 19
(
2
0
20
21
c, 3d, 3e ) were prepared according to the literature
22
optical rotation; [a] ZK2.8 (c 0.432, CH Cl ). Lit;
D
2
2
[
a] ZC23.5 (c 1, CH Cl ) of an (R)-isomer.
D 2 2
4
4.3.5. (R)-[2-(N,N-Dimethylaminomethyl)ferrocenyl]di-
phenylphosphine (3d). The enantiomeric excess was
4.2. General procedure for the deoxygenation of
sulfoxide
determined as 26% by an optical rotation; [a] ZC84 (c
D
2
1
0
.3, CHCl ). Lit; [a] ZC324 (c 0.5, CHCl ).
3 D 3
To a solution of sulfoxide (0.20 mmol) and TiCl4
(
0.3 mmol) in THF (2.5 mL) was added a solution of
triphenylphosphine (0.24 mmol) in THF (1.5 mL) and the
mixture was stirred at appropriate temperature under an
0
0
4.3.6. (S)-2,2 -Bis(diphenylphosphino)-1,1 -binaphthyl
(3e). The enantiomeric excess was determined as 4% by

S. Kikuchi et al. / Tetrahedron 61 (2005) 3587–3591
2a
3591
2
an optical rotation; [a] ZK8.5 (c 0.15, benzene). Lit;
7. For recent examples, see (a) Imamoto, T.; Oohara, N.;
Takahashi, H. Synthesis 2004, 1353. (b) Danjo, H.; Higuchi,
M.; Yada, M.; Imamoto, T. Tetrahedron Lett. 2004, 45, 603.
D
[
a] ZK229 (c 0.31, benzene).
D
(
c) Wada, Y.; Imamoto, T.; Tsuruta, H.; Yamaguchi, K.;
Acknowledgements
Gridnev, I. D. Adv. Synth. Catal. 2004, 346, 777. (d) Imamoto,
T.; Cr e´ py, K. V. L.; Katagiri, K. Tetrahedron: Asymmetry
2004, 15, 2213.
This work was financially supported by a Grant-in-Aid for
Scientific Research (C) from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
8
9
. Miyake, Y.; Yamaguchi, A.; Nishibayashi, Y.; Uemura, S.
Bull. Chem. Soc. Jpn 2003, 76, 381.
. De Jonge, C. R. H. I.; Hageman, H. J.; Huysmans, W. G. B.;
Mijis, W. J. J. Chem. Soc., Perkin Trans. 2 1973, 1276.
1
0. Meyers, C. Y.; Malte, A. M. J. Am. Chem. Soc. 1969, 91, 2123.
References and notes
11. Maercker, A.; Schuhmacher, R.; Buchmeier, W.; Lutz, H. D.
Chem. Ber. 1991, 124, 2489.
1
. (a) Solladi e´ , G. Synthesis 1981, 185. (b) Carreno, M. C. Chem.
Rev. 1995, 95, 1717. (c) Davies, S. G.; Loveridge, T.; Clough,
J. M. Synlett 1997, 66.
12. Yoshimura, T.; Yoshizawa, M.; Tsukurimichi, E. Bull. Chem.
Soc. Jpn. 1987, 60, 2491.
13. Evans, D. A.; Faul, M. M.; Colombo, L.; Bisaha, J. J.; Clardy,
J.; Cherry, D. J. Am. Chem. Soc. 1992, 114, 5977.
2
. House, H. O. Modern Synthetic Reactions 2nd ed.; Benjamin
Cummings: California, 1972; pp 15–16; see also pp 215–216.
. For reviews, see (a) Drabowicz, J.; Togo, H.; Mikolajczyk, M.;
Oae, S. Org. Prep. Proc. Int. 1984, 16, 171. (b) Madesclaire,
M. Tetrahedron 1988, 44, 6537. (c) Oae, S.; Togo, H. J. Synth.
Org. Chem., Jpn. 1982, 37, 812. (d) Still, I. W. J. In
Comprehensive Organic Synthesis; Pergamon: Oxford, 1991;
Vol. 8, p 403.
1
1
4. Solladie, G.; Hutt, J.; Girardin, A. Synthesis 1987, 173.
´
3
5. (a) Shimizu, T.; Kobayashi, M. J. Org. Chem. 1987, 52, 3399.
(
b) Ruano, J. L. G.; Alemparte, C.; Aranda, M. T.; Zarzuelo,
M. M. Org. Lett. 2003, 5, 75.
1
1
1
6. Hambley, T. W.; Raguse, B.; Ridley, D. D. Aust. J. Chem.
1
986, 39, 1833.
7. Rebiere, F.; Samuel, O.; Ricard, L.; Kagan, H. B. J. Org.
Chem. 1991, 56, 5991.
4
. (a) Szmant, H. H.; Cox, O. J. Org. Chem. 1966, 31, 1595. (b)
Luckenbach, R.; Herweg, G. Liebigs Ann. Chem. 1976, 2305.
8. (a) Duff, J. M.; Shaw, B. L. J. Chem. Soc., Dalton Trans. 1972,
(
c) Firouzabadi, H.; Karimi, B. Synthesis 1999, 500. (d) Miller,
S. J.; Collier, T. R.; Wu, W. Tetrahedron Lett. 2000, 41, 3781.
e) Shimizu, M.; Shibuya, K.; Hayakawa, R. Synlett 2000,
437. (f) Yoo, B.; Choi, K. H.; Kim, D. Y.; Choi, K. I.; Kim,
2
219. (b) Imamoto, T.; Kikuchi, S.; Miura, T.; Wada, Y. Org.
Lett. 2001, 3, 87.
(
1
2
2
9. Schmidt, U.; Riedl, B.; Griesser, H.; Fitz, C. Synthesis 1991,
1
6
55.
0. Terfort, A.; Brunner, H. J. Chem. Soc., Prekin Trans. 1 1996,
467.
J. H. Synth. Commun. 2003, 33, 53.
5
6
. (a) Kagoshima, H.; Hashimoto, Y.; Oguro, D.; Kutsuna, T.;
Saigo, K. Tetrahedron Lett. 1998, 39, 1203. (b) Kagoshima,
H.; Hashimoto, Y.; Saigo, K. Tetrahedron Lett. 1998, 39,
1
1. Hayashi, T.; Mise, T.; Fukushima, M.; Kagotani, M.;
Nagashima, N.; Hamada, Y.; Matsumoto, A.; Kawakami, S.;
Konishi, M.; Yamamoto, K.; Kumada, M. Bull. Chem. Soc.
Jpn. 1980, 53, 1138.
8
465. (c) Hashimoto, Y.; Kikuchi, S. Chem. Lett. 2002, 126.
d) Hashimoto, Y.; Konishi, H.; Kikuchi, S. Synlett 2004,
264. (e) Kikuchi, S.; Hashimoto, Y. Synlett 2004, 1267.
(
1
2
2. (a) Miyashita, A.; Takaya, H.; Souchi, T.; Noyori, R.
Tetrahedron 1984, 40, 1245. (b) Cai, D.; Payack, J. F.;
Bender, D. R.; Hughes, D. L.; Verhoeven, T. R.; Reider, P. J.
J. Org. Chem. 1994, 59, 7180. (c) Anger, D. J.; East, M. B.;
Eisenstadt, A.; Laneman, S. A. Chem. Commun. 1997, 235.
. There are a few reports using a similar combined reagent
besides our research (a) Palazzi, C.; Colombo, L.; Gennari, C.
Tetrahedron Lett. 1986, 27, 1735. (b) Gennari, C.; Colombo,
L.; Bertolini, G.; Schimperna, G. J. Org. Chem. 1987, 52,
2
754. (c) Takanami, T.; Suda, K.; Ohmori, H. Tetrahedron
Lett. 1990, 31, 677. (d) Kadota, I.; Gevorgyan, V.; Yamada, J.;
Yamamoto, Y. Synlett 1991, 823. (e) Suzuki, I.; Yamamoto, Y.
J. Org. Chem. 1993, 58, 4783. (f) Shi, M.; Jiang, J. K.; Cui,
S. C.; Feng, Y. S. J. Chem. Soc., Perkin Trans. 1 2001, 390. (g)
Sato, K.; Sekiguchi, T.; Ishihara, T.; Konno, T.; Yamanaka, H.
Chem. Lett. 2004, 33, 154.
23. Nakazumi, H.; Kitaguchi, T.; Ueyama, T.; Kitao, T. Synthesis
1984, 518.
24. Ogura, K.; Yamashita, M.; Tsuchihashi, G. Synthesis 1975,
385.
25. Luckenbach, R. Liebigs Ann. Chem. 1974, 1618.