Preparation of alkyl aryl sulfides from alcohols and 2- sulfanylbenzothiazole by a new type of oxidation-reduction condensation using aryl diphenylphosphinite and benzoquinone derivatives

Article abstract of DOI:10.1246/cl.2008.592

A method for the preparation of alkyl aryl sulfides from alcohols and 2-sulfanylbenzothiazole by a new type of oxidation-reduction condensation using phenyl diphenylphosphinite and 2.6-dimethoxy-1,4-benzoquinone is described. In this reaction, the chiral alcohols are converted into the corresponding chiral sulfides with almost complete inversion of configurations under mild and neutral conditions. Copyright

Full text of DOI:10.1246/cl.2008.592

5
92
Chemistry Letters Vol.37, No.6 (2008)
Preparation of Alkyl Aryl Sulfides from Alcohols and 2-Sulfanylbenzothiazole
by a New Type of Oxidation–Reduction Condensation Using Aryl Diphenylphosphinite
and Benzoquinone Derivatives
1
Ã1
Ã2
Kiichi Kuroda, Yujiro Hayashi, and Teruaki Mukaiyama
1
Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science,
Kagurazaka, Shinjuku-ku, Tokyo 162-8601
Center for Basic Research, The Kitasato Institute, 6-15-5 (TCI) Toshima, Kita-ku, Tokyo 114-0003
2
(Received March 4, 2008; CL-080238; E-mail: mukaiyam@abeam.ocn.jp)
A method for the preparation of alkyl aryl sulfides from
Table 1. Screening of phosphorus(III) compound
PX3III (1.1 equiv)
Me
alcohols and 2-sulfanylbenzothiazole by a new type of oxida-
tion–reduction condensation using phenyl diphenylphosphinite
and 2,6-dimethoxy-1,4-benzoquinone is described. In this
reaction, the chiral alcohols are converted into the corresponding
chiral sulfides with almost complete inversion of configurations
under mild and neutral conditions.
O
O
OH
N
S
(1.1 equiv)
SBtz
HS
Me
Ph
(
Ph
CHCl , rt, 6 h
3
1.0 equiv)
(1.0 equiv)
1
Entry
PX3
Yield/%a Entry
PX3
R
Yield/%a
Preparation of alkyl aryl sulfides is an important procedure
1
1
2
3
4
PPh3
PBu3
N.D.
5
R = H
64
54
in organic chemistry and, therefore many trials have been made
so as to develop synthetic methods. For example, the conversion
N.D.
6
OPPh2 R = Cl
P(OPh)3
N.D.
2
of alcohols into alkyl aryl sulfides by oxidation–reduction con-
densation using trivalent phosphorus compounds such as PPh3–
Ph PCl
8
7
R = OMe 58
2
aIsolated yield.
N
S
3
Btz =
DEAD–RSH (Mitsunobu conditions) or n-Bu3P–RSSR (Hata
4
conditions) is recognized useful and versatile. In these reaction
systems, chiral secondary sulfides were formed from chiral
secondary alcohols with complete inversion of configurations
by an SN2 pathway. However, it is generally known that sterical-
ly hindered tertiary alcohols are not converted to the correspond-
ing sulfides.
Table 2. Effects of quinone derivatives
Quinone (1.1 equiv)
OH
SBtz
PhOPPh (1.1 equiv)
2
BtzSH
Ph
(1.0 equiv)
Ph
CHCl , rt, 6 h
3
(1.0 equiv)
1
Recently, it was also shown from our laboratory that oxida-
5
Entry
Yield/%a
Entry
5
Yield/%a
Quinone
Quinone
tion–reduction condensation of alkyl diphenylphosphinites
(ROPPh2) with various nucleophiles (Nu–H) gave condensation
products (R–Nu) in the presence of benzoquinone derivatives as
t-Bu
61b
1
O
O
O
33
O
O
6
(
DBBQ)
t-Bu
oxidant. It is noteworthy that tertiary alcohols could be convert-
Me
OMe
ed into the corresponding tert-alkyl products by preparing a
key intermediate of the alkyl diphenylphosphinites from the cor-
responding alcohols and chlorodiphenylphosphine in advance.
When 2-sulfanylbenzothiazole (BtzSH) was employed as
sulfur nucleophile, chiral tert-alkyl diphenylphosphinites were
converted into inverted sulfides in the presence of 2,6-di-tert-
2
3
4
O
41
23
6
7
8
O
O
73
81)
c
(
(
DMOBQ)OMe
Cl
OMe
O
O
O
O
O
O
O
3
2
b–2d
butyl-1,4-benzoquinone (DBBQ).
To improve the synthetic
Cl
F
utility of this reaction system (ROPPh2–BQ–RSH), it is impor-
tant to develop a new method for direct synthesis of sulfides
from alcohols without forming an intermediate, ROPPh2.
In this communication, we would like to describe a new type
of oxidation–reduction condensation by the combined use of a
phosphorus compound and a benzoquinone derivative that was
successfully applied to the stereospecific syntheses of sulfides
from alcohols and 2-sulfanylbenzothiazole.
First, effects of phosphorus(III) compounds were examined
in order to choose a suitable reductant by taking condensation
reaction of 4-phenyl-2-butanol and 2-sulfanylbenzothiazole
in the presence of 2,6-dimethyl-1,4-benzoquinone (DMBQ) as
a model (Table 1). The desired sulfide 1 was not obtained when
a phosphine such as PPh3 and PBu3 or triphenylphosphite was
used (Entries 1–3). On the other hand, chlorodiphenylphosphine
Me
O
F
F
64
62)
3
c
(
(DMBQ)
Me
F
a
b
1
c
Isolated yield. Determined by H NMR analysis. Toluene was used instead of
CHCl3.
afforded 1 in 8% yield (Entry 4). In the case of aryl diphenyl-
7
phosphinites, the yield of 1 markedly increased (Entries 5–7).
As a result of examining the influence of substituents on the
aryl group, it was shown that phenyl diphenylphosphinite gave
a better result.
Next, various 1,4-benzoquinone derivatives were examined
to find a suitable oxidant (Table 2). A condensation reaction
using simple 1,4-benzoquinone afforded the desired product 1
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.6 (2008)
593
Table 3. Thioetherification of various alcohols
R
Ph Ph
ArO P
R
PhOPPh (1.5 equiv)
DMOBQ (1.5 equiv)
H
SBtz
2
OH
ArOPPh2
Ph Ph
O
O
O
O
SBtz
BtzSH
(1.1 equiv)
ROH
1
2
A
R
(
R
R1
R2
Toluene, rt, 6 h
1.0 equiv)
a
Yield/%
R
R
Entry
Product
b
(
%ee)
O
O
OH
ArO P
O
OH
SBtz
R2
Ph P
2
1
2
97
Ph
OH
OH
Ph
SBtz
SBtz
R1
'' Inversion''
OH
SBtz
ArOH
R1
R2 SBtz
98
90
R1
R2
Ph
Ph
O
O
B
C
3
4
5
OH
OH
OH
SBtz
Scheme 1.
SBtz
SBtz
89
99
formation of intermediate B. A subsequent nucleophilic attack
of alcohol to the positively charged phosphorus atom formed an
À
intermediate C along with elimination of aryloxy anion (ArO ).
À
(
>99)
Ph
Ph
Finally, nucleophilic attack of thiolate anion (BtzS ) to its
OH
SBtz
phosphonium part via SN2 manner gave the inverted sulfide.
Thus, a new type of oxidation–reduction condensation by
the combined use of PhOPPh2 and DMOBQ was established.
This reaction system was applicable to the thioetherification of
various alcohols including tertiary alcohol. In the case of chiral
alcohols, the inverted sulfides were obtained in good to excellent
yields under neutral mild conditions. Further study on this type
of condensation is now in progress.
7
96)
7
6
7
8
9
(
Ph
OH
Ph
SBtz
8
98)
7
(
3
3
OH
SBtz
8
(98)
5
EtO C
EtO C
2
2
OH
SBtz
6
86
5c
d
K. K. was granted a Research Fellowship of Japan Society
for the Promotion of Science for Young Scientist.
BnO C
BnO C
2
2
a
c
b
Isolated yield. Determined by HPLC using DAICEL CHIRALCEL OD-H.
The reaction was carried out by using BtzSH (2.0 equiv), DMOBQ (3.0 equiv),
d
References and Notes
and PhOPPh2 (3.0 equiv) for 24 h. The reaction was carried out by using BtzSH
1
a) D. J. Procter, J. Chem. Soc., Perkin Trans. 1 2001, 335. b) D. J.
Procter, J. Chem. Soc., Perkin Trans. 1 2000, 835. c) D. J. Procter,
J. Chem. Soc., Perkin Trans. 1 1999, 641. d) C. P. Baird, C. M.
Rayner, J. Chem. Soc., Perkin Trans. 1 1998, 1973.
(
2.0 equiv), DMBQ (3.0 equiv), and PhOPPh2 (3.0 equiv) for 17 h.
in lower yield compared to that of DMBQ (Entry 1). Introduc-
tion of one substituent at the 2-position of 1,4-benzoquinones
did not give good results (Entries 2 and 3) while the yield of
1
(
2
a) Y. Kawano, N. Kaneko, T. Mukaiyama, Chem. Lett. 2005, 34, 1612.
b) K. Ikegai, W. Pluempanupat, T. Mukaiyama, Bull. Chem. Soc. Jpn.
2
006, 79, 780. c) K. Ikegai, W. Pluempanupat, T. Mukaiyama, Chem.
Lett. 2005, 34, 638. d) T. Mukaiyama, K. Ikegai, Chem. Lett. 2004,
3, 1522.
improved when disubstituted 1,4-benzoquinones were used
Entries 4–6). The reaction with DMOBQ having electron-
3
donating 2,6-dimethoxy groups afforded 1 in 73% yield. On
the other hand, when electron-withdrawing groups are intro-
duced to benzoquinones, 1 was obtained in quite low yield
3
4
For a recent review for Mitsunobu reaction, see: T. Y. S. But, P. H.
Toy, Chem. Asian J. 2007, 2, 1340.
a) D. H. Valentine Jr., J. H. Hillhouse, Synthesis 2003, 317. b) J.
Skar z˙ ewski, A. Gupta, E. Wojaczy n´ ska, R. Siedlecka, Synlett 2003,
(
Entries 7 and 8). In the case of DMOBQ, the yield increased
1
1
615. c) H. Kotsuki, K. Matsumoto, H. Nishizawa, Tetrahedron Lett.
991, 32, 4155. d) I. Nakagawa, K. Aki, T. Hata, J. Chem. Soc., Perkin
Trans. 1 1983, 1315.
up to 81% by changing the solvent to toluene (Entry 6).
After a suitable reductant and an oxidant were chosen,
condensation of various alcohols were tried to investigate the
5
6
For reviews on oxidation–reduction condensation, see: a) T.
Mukaiyama, H. Yamabe, Chem. Lett. 2007, 36, 2. b) T. Mukaiyama,
K. Ikegai, H. Aoki, W. Pluempanupat, K. Masutani, Proc. Jpn. Acad.,
Ser. B 2005, 81, 103. c) T. Mukaiyama, Angew. Chem., Int. Ed. 2004,
8
scope of this reaction (Table 3). The reactions of primary alco-
hols having olefin and a furan ring or cyclic secondary alcohols
proceeded smoothly to afford the corresponding sulfides in high
yields (Entries 1–4). Next, thioetherification of chiral secondary
alcohols was examined and the inverted products were obtained
in good to excellent yields with almost complete inversions of
stereochemistries even when acetylene and ethyl ester groups
coexisted in the same molecules (Entries 5–8). Further, the
reaction of a sterically hindered tertiary alcohol gave the desired
product in high yield when DMBQ was employed instead of
DMOBQ (Entry 9).
Based on the above results, it was assumed that this conden-
sation reaction proceeded as shown in Scheme 1: the reaction of
aryl diphenylphosphinite (ArOPPh2) and benzoquinone deriva-
tive initially gave a zwitterionic intermediate A and, the follow-
ing deprotonation of BtzSH by phenoxide anion resulted in the
4
3, 5590.
For examples, see: a) K. Kuroda, Y. Hayashi, T. Mukaiyama, Tetra-
hedron 2007, 63, 6358. b) K. Masutani, T. Minowa, Y. Hagiwara, T.
Mukaiyama, Bull. Chem. Soc. Jpn. 2006, 79, 1106. c) H. Aoki, K.
Kuroda, T. Mukaiyama, Chem. Lett. 2005, 34, 1266. d) T. Mukaiyama,
H. Aoki, Chem. Lett. 2005, 34, 142. e) T. Mukaiyama, T. Shintou, K.
Fukumoto, J. Am. Chem. Soc. 2003, 125, 10538.
7
8
Aryl diphenylphosphinites are prepared according to a procedure for
alkyl diphenylphosphinites, see ref. 2c.
Typical experimental procedure is as follows (Table 3, Entry 5): to a
solution of PhOPPh2 (125.2 mg, 0.45 mmol) and (S)-(+)-4-phenyl-2-
butanol (45.1 mg, 0.30 mmol) in dry toluene (1.50 mL) were added
BtzSH (55.2 mg, 0.33 mmol) followed by DMOBQ (75.7 mg, 0.45
mmol) at rt under argon atmosphere. The reaction mixture was stirred
for 6 h and the crude product was purified by preparative TLC to the
corresponding sulfide (89.2 mg, 99%).
Published on the web (Advance View) April 26, 2008; doi:10.1246/cl.2008.592