Stereospecific synthesis of alkyl aryl sulfides from alcohols and 2-sulfanylbenzothiazole using aryl diphenylphosphinite and azide compounds by a new type of oxidation-reduction condensation

Article abstract of DOI:10.1246/cl.2008.836

The preparation of alkyl aryl Sulfides from alcohols and 2-sulfanylbenzothiazole using phenyl diphenylphosphinite and azide compounds by a new type of oxidation-reduction condensation is described. The chiral secondary and tertiary alcohols are converted

Full text of DOI:10.1246/cl.2008.836

836
Chemistry Letters Vol.37, No.8 (2008)
Stereospecific Synthesis of Alkyl Aryl Sulfides from Alcohols and 2-Sulfanylbenzothiazole
Using Aryl Diphenylphosphinite and Azide Compounds
by a New Type of Oxidation–Reduction Condensation
Kiichi Kuroda,1 Yuji Maruyama,2 Yujiro Hayashi,Ã1 and Teruaki MukaiyamaÃ3
1Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601
2Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601
3Center for Basic Research, Kitasato University, 6-15-5 (TCI) Toshima, Kita-ku, Tokyo 114-0003
(Received May 26, 2008; CL-080530; E-mail: mukaiyam@abeam.ocn.jp)
The preparation of alkyl aryl sulfides from alcohols and
2-sulfanylbenzothiazole using phenyl diphenylphosphinite and
azide compounds by a new type of oxidation–reduction conden-
sation is described. The chiral secondary and tertiary alcohols
are converted into the corresponding chiral sulfides with almost
complete inversion of configurations under mild and neutral
conditions.
Table 1. Screening of phosphorus(III) compounds
PX3III (1.1 equiv)
OH
SBtz
Me
N3CH2CO2Et (1.1 equiv)
BtzSH
Ph
Me
Ph
1,2-Dichloropropane
reflux, 3 h
1a (1.0 equiv)
2a
Yield/%a
(1.0 equiv)
Yield/%a
trace
Entry
1
PX3
Entry
PX3
PPh3
PBu3
5
6
7
8
11
69
65
Ph2PCl
R
2
3
4
N.D.
34
R = H
R = Cl
A reaction of organic azides1 with trivalent phosphorous
compounds that affords the corresponding iminophosphoranes
(aza-ylides) is known as ‘‘the Staudinger reaction.’’2 This reac-
tion has become one of the most widely used synthetic tools in
organic chemistry3 and biology4 as well because of versatile
properties of iminophosphoranes: namely, 1) primary amines
are given by hydrolysis with water, 2) the corresponding imines
are afforded by the reaction with carbonyl compounds (the aza-
Wittig reaction). However, there are only few reports on the in-
termolecular dehydration condensation reactions between alco-
hols and acidic components via this key intermediate, imino-
phosphorane, except for condensation reaction of carboxylic
acids or imides with primary alcohols by the combined use of tri-
phenylphosphine and benzyl azide.5 Although it provides O- and
N-alkylated products under neutral conditions, secondary or ter-
tiary alcohols were not used as substrates in this reaction system
and also a condensation reaction of thiols with alcohols was not
examined.
P(OPh)3
OPPh2
PhP(OPh)2
58
R = OMe 61
aIsolated yield.
N
Btz =
S
Table 2. Screening of azide compounds
PhOPPh2 (1.1 equiv)
Azide (1.1 equiv)
OH
Me
SBtz
Me
BtzSH
Ph
1a (1.0 equiv)
Ph
1,2-Dichloropropane
reflux, 3 h
2a
(1.0 equiv)
Yield/%a
Yield/%a
Entry
1
Azide
Entry
4
Azide
53
34
N3
TMS
N3
O
2
3
67 (81)b
69 (84)b
5
6
N.D.
7
N3
N3
Ph
(PhO)2P N3
TMSN3
CO2Et
Recently, a new type of oxidation–reduction condensation6
was reported from our laboratory by using the combination of
aryl diphenylphosphinite (ArOPPh2) and benzoquinone deriva-
tives, which was employed in the syntheses of sulfides from al-
cohols and a sulfur nucleophile such as 2-sulfanylbenzothia-
zole.7 It is noteworthy that this dehydration condensation pro-
ceeded under mild and neutral conditions to produce chiral sul-
fides from chiral alcohols with almost complete inversion of
their stereochemistries. This is the first example of aryl diphenyl-
phosphinite to be employed in oxidation–reduction condensation
as a reductant. In order to extend the utility of this aryl diphenyl-
phosphinite, our attention was next focused on oxidation–reduc-
tion condensation using organic azide8 as oxidant in stead of
benzoquinone derivatives.
aIsolated yield. bToluene was used instead of 1,2-dichloropropane.
densation reaction of 4-phenylbutan-2-ol and 2-sulfanylbenzo-
thiazole in the presence of ethyl azidoacetate as a model
(Table 1). Then, it was shown that the desired sulfide 2a was
not obtained when PPh3 or PBu3 was used (Entries 1 and 2)
while it was afforded by the use of P(OPh)3, PhP(OPh)2, and
Ph2PCl (Entries 3–5). In the case of using aryl diphenylphos-
phinites, the yield of 2a markedly increased (Entries 6–8)
and phenyl diphenylphosphinite (PhOPPh2) was among the best
(Entry 6).
Next, various azide compounds were examined in order
to find a suitable oxidant (Table 2), and a condensation reaction
using trimethylsilylmethyl azide afforded the desired product 2a
in moderate yield (Entry 1). The alkly azide such as benzyl azide
or ethyl azidoacetate gave 2a in good yields while 1-azidoada-
mantane, diphenylphosphoryl azide, or trimethylsilyl azide
did not work well (Entries 2–6). In the cases of benzyl azide
and ethyl azidoacetate, the yields increased up to 81 and 84%
by changing the solvent from 1,2-dichloropropane to toluene
(Entries 2 and 3).
In this communication, we would like to describe a new
method for stereospecific synthesis of sec- and tert-alkyl aryl
sulfide from alcohols and 2-sulfanylbenzothiazole by a new
type of oxidation–reduction condensation using a phosphorus
compound and an azide.
In order to find the most suitable reductant, effects of phos-
phorus(III) compounds were first examined by taking the con-
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.8 (2008)
837
Table 3. Thioetherification of various chiral alcohols
Ph Ph
ArO P N R
Ph Ph
ArO P N R
H
SBtz
PhOPPh2 (1.5 equiv)
N3CH2CO2Et (1.5 equiv)
ArOPPh2
RN3
R1 OH
R1 SBtz
R2 R3
BtzSH
N2
Iminophosphorane
R2
R3
Toluene
1 (1.0 equiv)
(1.1 equiv)
2
Ph Ph
ArO P N R
Yield/%a
(%ee)b
Ph
P
H
R1 SBtz
Ph
R1
R2
Entry
1
Temp., Time
ROH
1
Product 2
O
N R
H
H
R1 OH
O
Ph2P NR
R2
R3
OH
Me
SBtz
Me
99
(>99)
SBtz ArOH
R3
1b 40 °C, 24 h
R2
R3
SBtz
'' Inversion''
Ph
Ph
A
B
OH
SBtz
Me
SBtz
83
2c
1c
1d
rt, 12 h
rt, 24 h
(97)
Scheme 1.
Ph
Me
Ph
OH
the reaction of aryl diphenylphosphinite (ArOPPh2) and azide
compound initially gave an iminophosphorane and the following
deprotonation of BtzSH by iminophosphorane resulted in the
formation of intermediate A. Subsequent nucleophilic attack
of alcohol to the positively charged phosphorus atom led to an
intermediate B. Finally, a nucleophilic attack of the thiolate
anion (BtzSÀ) to its phosphonium part via SN2 manner gave
the inverted sulfide.
89
(98)
3c
4
3
3
OH
SBtz
1e 80 °C, 6 h
1f 40 °C, 48 h
85
Me OH
Et CO2Bn
Me SBtz
5d
76
(>99)
Et
CO2Bn
Thus, a new type of oxidation–reduction condensation by
the combined use of aryl diphenylphosphinite and azide com-
pounds was established. Chiral sec- or tert-alkyl sulfides were
formed from the corresponding chiral alcohols with almost com-
plete inversion of configuration under mild and neutral condi-
tions. This is the first example of the stereospecific synthesis
of an inverted chiral tertiary thiol from a chiral tertiary alcohol
by an SN2 displacement except in the case of the previously re-
ported oxidation–reduction condensation using alkyl diphenyl-
phosphinite.10
Me OH
Ph CO2Me
Me OH
CO2Et
(92%ee)
Me SBtz
90
6d,e
1g
40 °C, 48 h
(99)
Ph
CO2Me
Me SBtz
CO2Et
7c,d
87
(92)
1h 27 °C, 48 h
Ph
Ph
b
c
aIsolated yield. Determined by HPLC analysis. The solution of
PhOPPh2 and ethyl azidoacetate was stirred at 80 ꢀC for 20 min,
followed by addition of alcohol and BtzSH at rt. dThe reaction
was carried out by using BtzSH (4.0 equiv), PhOPPh2 (4.0 equiv),
e
K. K. was granted a Research Fellowship of Japan Society
for the Promotion of Science for Young Scientist.
and ethyl azidoacetate (4.0 equiv). Ref 9.
After a suitable reductant and an oxidant were selected,
condensations of various chiral alcohols were tried in order to
examine the scope of this reaction under the optimized condi-
tions (Table 3). A reaction of chiral secondary alcohol 1b pro-
ceeded smoothly to afford the corresponding sulfide in quantita-
tive yield with complete inversion of stereochemistry (Entry 1).
Chiral benzylic alcohol 1c was also successfully used in this
reaction (Entry 2) and the reaction of 2-propynylic alcohol 1d
gave the desired product in high yield with high enantiomeric
excess (Entry 3). The thioetherification of sterically hindered
(À)-menthol (1e) gave the inverted product in high yield without
any other products (Entry 4). Further, more-hindered tertiary al-
cohols were employed as substrates in order to investigate poten-
tial application of this reaction to the asymmetric construction of
quaternary carbon (Entries 5–7). Then, the reaction of chiral ter-
tiary alcohol 1f proceeded smoothly to afford the corresponding
sulfide in good yield with complete inversion of stereochemistry
(Entry 5). Similarly, chiral benzylic alcohol 1g bearing the ꢀ-es-
ter group gave the desired product in high yield with excellent
enantiomeric excess (Entry 6). Also, thioetherification of chiral
2-propynylic alcohol 1h gave the inverted product in high yield
(Entry 7).
References and Notes
1
2
3
For a review of organic azides, see: S. Brase, C. Gil, K. Knepper, V.
¨
Zimmermann, Angew. Chem., Int. Ed. 2005, 44, 5188.
For a review of the Staudinger reaction, see: Y. G. Gololobov, L. F.
Kasukhin, Tetrahedron 1992, 48, 1353.
a) P. Molina, M. J. Vilaplana, Synthesis 1994, 1197. b) P. M. Fresneda,
P. Molina, Synlett 2004, 1. c) S. Eguchi, Arkivoc 2005 Part ii, 98. d) F.
Palacios, C. Alonso, D. Aparicio, G. Rubiales, J. M. de los Santos, Tetra-
hedron 2007, 63, 523.
4
a) E. Saxon, C. R. Bertozzi, Science 2000, 287, 2007. b) E. Saxon, S. J.
Luchansky, H. C. Hang, C. Yu, S. C. Lee, C. R. Bertozzi, J. Am. Chem.
Soc. 2002, 124, 14893. c) M. Kohn, R. Breinbauer, Angew. Chem., Int.
Ed. 2004, 43, 3106.
¨
5
6
S. Torii, H. Okumoto, M. Fujikawa, M. A. Rashid, Chem. Express. 1992,
7, 933.
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, 43, 5590.
K. Kuroda, Y. Hayashi, T. Mukaiyama, Chem. Lett. 2008, 37, 592.
For oxidation–reduction condensation using azides, see: a) H. Aoki, K.
Kuroda, T. Mukaiyama, Chem. Lett. 2005, 34, 1266. b) T. Mukaiyama,
K. Kuroda, H. Aoki, Chem. Lett. 2005, 34, 1644.
7
8
9
Typical experimental procedure is as follows (Table 3, Entry 6): to a
solution of PhOPPh2 (222.6 mg, 0.80 mmol) and chiral alcohol 1g
(35.8 mg, 0.199 mmol) in dry toluene (0.60 mL) were added BtzSH
(133.8 mg, 0.80 mmol) followed by ethyl azidoacetate (103.3 mg, 0.80
mmol) at rt under an argon atmosphere. The reaction mixture was stirred
at 40 ꢀC for 48 h and the crude product was purified by preparative TLC to
the corresponding sulfide (58.9 mg, 90%).
Since the chiral tert-alkyl Btz sulfide was converted to the
corresponding chiral tertiary thiol in high yield by treating with
LiAlH4,10 a concise method for the preparation of chiral tertiary
thiol from the corresponding alcohols was established.
10 For condensation of 2-sulfanylbenzothiazole with alkyl diphenyl-
phosphinite (ROPPh2) prepared from alcohols, see: K. Ikegai, W.
Pluempanupat, T. Mukaiyama, Bull. Chem. Soc. Jpn. 2006, 79, 780.
A plausible reaction mechanism is shown in Scheme 1:
Published on the web (Advance View) July 5, 2008; doi:10.1246/cl.2008.836