Conversion of alcohols to alkyl aryl sulfides by a new type of oxidation-reduction condensation using phenyl diphenylphosphinite

Article abstract of DOI:10.1246/bcsj.82.381

Preparation of alkyl aryl sulfides from alcohols and arenethiols such as 2-sulfanyl-1,3-benzothiazole (BtzSH) is described by a new type of oxidation-reduction condensation using phenyl diphenylphosphinite (PhOPPh ₂) and benzoquinone derivatives or azide compounds. This reaction proceeds under mild and neutral conditions and is applicable to the thioetherification of various alcohols in which the chiral secondary and tertiary alcohols are converted into the corresponding chiral sulfides with almost complete inversion of configuration.

Full text of DOI:10.1246/bcsj.82.381

© 2009 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 82, No. 3, 381–392 (2009)
381
Conversion of Alcohols to Alkyl Aryl Sulfides by a New
Type of Oxidation-Reduction Condensation
Using Phenyl Diphenylphosphinite
Kiichi Kuroda,1 Yuji Maruyama,2 Yujiro Hayashi,*1 and Teruaki Mukaiyama*3
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 August 11, 2008; E-mail: mukaiyam@abeam.ocn.ne.jp
Preparation of alkyl aryl sulfides from alcohols and arenethiols such as 2-sulfanyl-1,3-benzothiazole (BtzSH) is
described by a new type of oxidation-reduction condensation using phenyl diphenylphosphinite (PhOPPh2) and
benzoquinone derivatives or azide compounds. This reaction proceeds under mild and neutral conditions and is applicable
to the thioetherification of various alcohols in which the chiral secondary and tertiary alcohols are converted into the
corresponding chiral sulfides with almost complete inversion of configuration.
Preparation of various alkyl aryl sulfides is an important
synthetic process in organic chemistry1 and therefore many
trials have been made to develop useful synthetic methods. For
example, a nucleophilic substitution of activated alkyl halides
or sulfonates with aryl thiolate prepared from aryl thiol in the
presence of strong base2 is a fundamental methodology. Since
the synthetic scope of this classical reaction is generally limited
due to the harsh conditions (long reaction time and high
reaction temperature), alternative methods for alkyl aryl
sulfides have recently been studied.3,4 On the other hand,
direct substitution reactions of alcohols by thiolate anion
under mild and neutral conditions is considered to be most
attractive and efficient. Procedures developed previously by
Mitsunobu et al. or Hata et al. based on the concept of
“oxidation-reduction condensation”5 are known to be useful
for this transformation: that is, alcohols are converted into the
corresponding sulfides or thioesters by treating with weakly
acidic sulfur nucleophiles such as arenethiols or thioacetic
acids in the presence of triphenylphosphine and diethyl
azodicarboxylate (DEAD)6,7 or with tributylphosphine and
diaryl disulfides.8 In these reaction systems,9 primary and
secondary alcohols are the most suitable substrates, and chiral
secondary sulfides and thioesters are formed from chiral
secondary alcohols with complete inversion of configuration
by an SN2 displacement. However, it is generally known that
the sterically hindered tertiary alcohols are not converted to the
corresponding tertiary sulfides10 because the starting alcohols
are recovered or undesired olefins are produced exclusively by
elimination reactions. Thus, nucleophilic substitution at qua-
ternary carbon centers via SN2 displacement has been a very
difficult problem and one of the most challenging topics in
current organic synthesis.11
reduction condensation12 of alkyl diphenylphosphinites
(ROPPh2), that were prepared from the corresponding alcohols,
with various nucleophiles (Nu-H) gave the formal dehydrated
condensation products (R-Nu) in the presence of benzoquinone
derivatives as oxidants.13-16 It is noteworthy that the tertiary
alcohols are converted into the corresponding tert-alkyl
products by preparing the intermediates of the alkyl diphenyl-
phosphinites from the corresponding alcohols and chlorodi-
phenylphosphine in advance. When 2-sulfanyl-1,3-benzothia-
zole (BtzSH) was employed as a sulfur nucleophile in the
presence of 2,6-di-tert-butyl-1,4-benzoquinone (DBBQ), chiral
tert-alkyl diphenylphosphinites were converted into the corre-
sponding chiral tert-alkyl sulfides with inversion of config-
uration.16 In this reaction, the yields and enantiomeric excesses
of the desired Btz sulfides are influenced by the ¡-substituents
of alcohols. For example, chiral tert-alkyl sulfides are obtained
in good yields with complete inversion of configuration when
tert-alcohols having ¡-ester groups are employed as the starting
materials (Scheme 1). The chiral tert-alkyl Btz sulfide obtained
is converted to the corresponding chiral tert-thiol in high yield
on treatment with LiAlH4.
In order to improve the synthetic utility of this reaction
system (ROPPh2-BQ-BtzSH), it is important to develop a new
method for one-pot synthesis of sulfides from alcohols without
preparing the intermediate, ROPPh2. Recently, a newer type of
oxidation-reduction condensation by using a combination of
aryl diphenylphosphinite (ArOPPh2) and benzoquinone deriv-
atives17 or azide compounds18 was reported from our labo-
ratory, which was then applied to the direct synthesis of sulfides
from alcohols and 2-sulfanyl-1,3-benzothiazole (BtzSH) as a
sulfur nucleophile. In this paper, we would like to report on
these condensation reactions to further examine the scope and
limitation.
It has been reported from our laboratory that the oxidation-
Published on the web March 12, 2009; doi:10.1246/bcsj.82.381

382
Bull. Chem. Soc. Jpn. Vol. 82, No. 3 (2009)
Synthesis of Alkyl Aryl Sulfides
tBu
N
S
N
O
O
HS
ClPPh2
Me OH
Me OPPh2
S
S
Me
tBu
Et3N, DMAP
(1.0 equiv) (2.0 equiv)
CHCl3, rt
∗
∗
Ph
CO2Me
∗
Ph
CO2Me
Ph
CO2Me
THF, rt
99%
(2.0 equiv)
(>99%ee)
73%, 99%ee
Me SH
OH
LiAlH4
Et2O, reflux
∗
Ph
95%
Scheme 1.
Table 2. Screening of Quinone Derivatives
Table 1. Screening of Phosphorus(III) Compound
PX3 (1.1 equiv)
Me
Quinone (1.1 equiv)
OH
SBtz
Me
PhOPPh2 (1.1 equiv)
BtzSH
Ph
Me
Ph
O
O
CHCl3, rt, 6 h
1a (1.0 equiv)
(1.0 equiv)
2a
OH
Me
SBtz
Me
(1.1 equiv)
BtzSH
(1.0 equiv)
N
Me
Entry Quinone Yield/%a) Entry
Quinone
Yield/%a)
Ph
1a (1.0 equiv)
Ph
CHCl3, rt, 6 h
2a
tBu
1
2
3
4
O
O
O
33
46
23
64
5
6
7
8
61b)
O
O
Btz =
S
tBu
(DBBQ)
OMe
O
Yield
/%a)
Yield
/%a)
Entry
PX3
Entry
PX3
O
73
3
O
O
1
2
3
4
PPh3
PBu3
P(OPh)3 N.D.
PhP(OPh)2 21
N.D.
N.D.
5
6
7
8
Ph2PCl
8
64
54
(DMOBQ)
OMe
Cl
R = H
R = Cl
R
OMe
O
OPPh2
O
O
R = OMe 58
Cl
F
a) Isolated yield.
F
O
O
O
O
F
3
(DMBQ)
Results and Discussion
F
1
Preparation of Alkyl Aryl Sulfides from Alcohols and 2-
Sulfanyl 1,3-Benzothiazole (BtzSH) by Oxidation-Reduc-
tion Condensation Using Phenyl Diphenylphosphinite
and Benzoquinone Derivatives. Initially effects of phos-
phorus(III) compounds were examined in order to find
a suitable reductant by taking condensation reaction of
4-phenylbutan-2-ol (1a) and 2-sulfanyl-1,3-benzothiazole
(BtzSH) in the presence of 2,6-dimethyl-1,4-benzoquinone
(DMBQ) as a model (Table 1). The desired sulfide 2a was not
obtained when PPh3, PBu3, and P(OPh)3 were used (Entries
1-3) while PhP(OPh)2 and Ph2PCl afforded 2a in low yields
(Entries 4 and 5). In the case of aryl diphenylphosphinites,
the yield of 2a markedly increased (Entries 6-8). As a result of
examination of the influence of substituents on the aryl group,
it was shown that the phenyl diphenylphosphinite (PhOPPh2)
gave the best result (Entry 6).
Next, various 1,4-benzoquinone derivatives were examined
to find a suitable oxidant (Table 2). A condensation reaction
that used simple 1,4-benzoquinone afforded the desired product
2a in lower yield compared to that of DMBQ (Entry 1).
Introduction of one substituent at the 2-position of 1,4-
benzoquinones did not give good results (Entries 2 and 3)
while the yield improved if disubstituted 1,4-benzoquinones
were used (Entries 4-6). The reaction with 2,6-dimethoxy-1,4-
benzoquinone (DMOBQ) afforded 2a in 73% yield. On the
a) Isolated yield. b) Determined by H NMR analysis.
other hand, when electron-withdrawing groups were introduced
to benzoquinones, 2a was obtained in quite low yield
(Entries 7 and 8).
The effect of the solvent was next examined in the
condensation of alcohol 2a with BtzSH in the presence of
PhOPPh2 and DMOBQ (Table 3). Whereas polar solvents such
as Et2O, THF, and EtOAc lowered the yield of the desired
sulfide 2a (Entries 1-3), CH3CN or halogenated solvents gave
better yields (Entries 4-6), and toluene was among the best
(Entry 7).
After a suitable reductant and an oxidant were chosen,
condensation reactions of various alcohols with BtzSH were
tried to investigate the scope of this reaction under the
optimized conditions (Table 4). Reactions of benzyl alcohol
(1b), allyl alcohols 1c, and primary alcohol 1d having a furan
ring proceeded smoothly to afford the corresponding sulfides in
high yields (Entries 1-3). Primary alcohols 1e and 1f with a
ketone group and a tert-butyldimethylsilyl group were also
converted into the corresponding sulfides in good yields while
alcohols 1g and 1h bearing indole and a N-tert-butoxycarbonyl
group retarded the thioetherification under the above conditions
(Entries 4-7). Cyclic secondary alcohol 1i was successfully
used in this reaction (Entry 8). Further, the reactions of various

K. Kuroda et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 3 (2009)
383
Table 3. Effect of Solventa)
Table 5. Thioetherification of Various Alcohols
PhOPPh2 (1.5 equiv)
DMOBQ (1.5 equiv)
R1 OH
R1 SBtz
R2 R3
Entry
Solvent
Yield/%
BtzSH
R2
R3
1
2
3
4
5
6
7
Et2O
THF
42
N.D.
50
64
71
Toluene, rt, 6 h
1 (1.0 equiv)
(1.1 equiv)
2
EtOAc
CH3CN
CH2Cl2
CHCl3
Toluene
Yield/%a)
(%ee)b)
Entry
ROH
1 (%ee)
Product
2
OH
Me
SBtz
Me
99
(>99)
73
81 (62)b)
1
2
1a (>99)
1n (>99)
1o (98)
2a
2n
2o
Ph
Ph
OH
SBtz
Me
a) The reactions were carried out by using 1a (1.0 equiv),
BtzSH (1.0 equiv), PhOPPh2 (1.1 equiv), and DMOBQ (1.1
equiv). b) DMBQ was used instead of DMOBQ.
77
(96)
Ph
OH
Me
Ph
SBtz
87
(98)
3
4
3
3
Table 4. Thioetherification of Various Alcohols
OH
Me
OH
SBtz
85
(98)
PhOPPh2 (1.5 equiv)
DMOBQ (1.5 equiv)
1p (>99)
2p
2q
EtO2C
EtO2C
Me
ROH
BtzSH
R
SBtz
SBtz
Toluene, rt, 6 h
1 (1.0 equiv)
(1.1 equiv)
2
5c)
1q
62
Yield
Entry
1
ROH
1
Product
2
/%a)
Me OH
Et CO2Bn
Me OH
Ph CO2Me
Me SBtz
55
(>99)
6d),e)
7d)
1r (>99)
1s (>99)
2r
2s
Et
CO2Bn
1b
1c
2b
2c
97
98
Ph
OH
OH
Ph
SBtz
SBtz
Me SBtz
Ph CO2Me
2
56
(>99)
Ph
Ph
OH
SBtz
3
1d
2d
90
O
O
a) Isolated yield. b) Determined by HPLC analysis. c) The
reaction was carried out by using BtzSH (2.0 equiv), DMOBQ
(3.0 equiv), and PhOPPh2 (3.0 equiv) for 24 h. d) The reaction
was carried out by using BtzSH (4.0 equiv), DMBQ (4.0 equiv),
and PhOPPh2 (4.0 equiv) for 24 h. e) When DBBQ was used
instead of DMBQ, the desired sulfide 2r was obtained in 52%
yield with >99%ee.
Ph
Ph
OH
SBtz
4
5
1e
2e
81
78
O
O
OH
SBtz
1f
2f
TBSO
TBSO
OH
SBtz
6
1g
2g
69
N
N
H
H
OH
OH
Me OH
SBtz
SBtz
Me SBtz
7
8
1h
2h
49
89
BocHN
BocHN
Taking the above results into consideration, thioetherifica-
tion of various chiral alcohols was next tried in order to
examine the stereochemistry of this reaction (Table 5). It was
shown that the desired sulfides were obtained in good to
excellent yields with almost complete inversions of stereo-
chemistry even when acetylene and ethyl ester groups coexisted
in the same molecules (Entries 1-4). This suggests that the
reaction basically proceeded via SN2 mechanism. Since the
reaction of chiral benzylic alcohol 1n afforded the desired
product with slightly lowered optical purity, it is considered
that this reaction proceeded partially via SN1 mechanism as
the benzylic cation was generated more easily (Entry 2). The
thioetherification of sterically-hindered (¹)-(l)-menthol (1q)
gave the inverted product in moderate chemical yield without
any other accompanying products (Entry 5). Further, more
hindered tertiary alcohols were employed as substrates in
order to study the potential application of this reaction to
the asymmetric construction of quaternary carbon (Entries 6
and 7). The reactions of chiral tertiary alcohol 1r and chiral
benzylic alcohol 1s bearing ¡-ester groups afforded the
corresponding sulfides in moderate yields with complete
inversion of configuration.
1i
2i
87
79c)
9b)
1j
2j
2k
2l
Me
CO2Me
Me OH
Me
Me
CO2Me
Me SBtz
Me
10b)
1k
42
20
Ph
Ph
O
O
Me OH
Ph Me
Me OH
Me
Me SBtz
11b)
12b)
1l
Ph
Me
Me SBtz
1m
2m <15
Ph
Ph
Me
a) Isolated yeild. b) The reaction was carried out by using
BtzSH (2.0 equiv), DMBQ (2.0 equiv), and PhOPPh2 (2.0
equiv) at 40 °C for 24 h. c) DMOBQ was used instead of
DMBQ.
tertiary alcohols were next tried (Entries 9-12). Although tert-
alcohol 1j having an ¡-ester group was converted into the
corresponding sulfide in 79% yield, the yield was improved to
87% when DMBQ was used instead of DMOBQ (Entry 9).
tert-Alcohol 1k with an ¡-ketone group gave the desired
product in moderate yield but the yield of the desired sulfide
markedly decreased when alcohol 1l bearing an ¡-phenyl
group and aliphatic alcohol 1m were used (Entries 10-12).
In order to extend the scope of this condensation reaction,
reactions of various arenethiols or thiobenzoic acid with
tertiary alcohol 1j were examined (Table 6). When benzene-
thiol (pKa 7.76 in EtOH/H2O, 10.3 in DMSO)19a was used as a

384
Bull. Chem. Soc. Jpn. Vol. 82, No. 3 (2009)
Synthesis of Alkyl Aryl Sulfides
Table 6. Condensation of Tertiary Alcohol 1j with Various ArSH
PhOPPh2 (2.0 equiv)
Me OH
Me SAr
Me CO2Me
DBBQ (2.0 equiv)
ArSH
Me
CO2Me
Toluene, 40 °C, 24 h
1j (1.0 equiv)
(2.0 equiv)
3
Entry
1
ArSH
Product 3 Yield/%a) Entry
ArSH
Product 3 Yield/%a)
N
N
N
HS
3a
83
6
3f
68
HS
N
Me
N
2
3
4
5
3b
3c
3d
3e
72
7
8
2j
3g
3h
3i
90 (87)b)
83
HS
HS
HS
HS
NO2
S
N
78
OMe
S
N
NO2
N
67 (N.D.)b)
91 (21)b)
9
82 (80)b)
19
HS
HS
HS
HS
O
O
N
10
NO2
Ph
a) Isolated yield. b) DMBQ was used instead of DBBQ.
R
R
Ph Ph
H SBtz
PhO P O
O
PhOPPh2
O
O
A
R
R
R
R
R
Ph Ph
PhO P O
R
O
O
OH
OH
SBtz
R2
O
Ph2P
R1
SN2
Ph2P O
OH
R
R
R1
OH
PhOH
R2
'' Inversion''
SBtz
SBtz
R1
R2
B
C
Scheme 2.
sulfur nucleophile, the desired sulfide was obtained in good
yield (Entry 1). The reactions of 1j with 4-nitrobenzenethiol
(pKa 5.11 in EtOH/H2O, 5.5 in DMSO)19a or 4-methoxy-
benzenethiol (pKa 7.99 in EtOH/H2O, 11.2 in DMSO)19a
proceeded in a similar fashion to afford the corresponding
sulfides in good yields (Entries 2 and 3). Thus, the effect of
pKa values of nucleophiles12,14c,14d,20 was not observed in the
case of benzenethiol derivatives. On the other hand, it was
shown that the reactivity of 5-nitro-2-sulfanylpyridine was
higher than that of 2-sulfanylpyridine whose difference may be
attributed to the pKa values of nucleophiles (Entries 4 and 5).
Further, the reactions of various heteroarene thiols were
examined (Entries 6-9). It was found then that 1-methyl-1H-
tetrazole-5-thiol could also be used successfully in this reaction
(Entry 6), and 2-sulfanyl-1,3-benzothiazole (BtzSH; pKa 7.00
in EtOH/H2O)19b was the most reactive of the heteroarene
derivatives (Entry 7). When thiobenzoic acid (pKa 5.3 in
DMSO)19c was used, the yield of the desired product was poor
though its acidity was sufficient (Entry 10).
DBBQ gives initially the betain intermediate A, and deproto-
nation of BtzSH by phenoxide anion that follows results in the
formation of intermediate B. A subsequent nucleophilic attack
of alcohol to the positively charged phosphorus atom leads to
the formation of an intermediate C along with the elimination
¹
of phenoxide anion (PhO ). Finally, a nucleophilic attack of
¹
thiolate anion (BtzS ) to the carbon atom adjacent to an oxygen
atom of alkoxy group via SN2 manner gives the inverted
sulfide. The reason why PhOPPh2 among phosphorus com-
pounds gave the best result is considered as follows. Nucleo-
philicity of a phosphorus compound to benzoquinone deriva-
tives is essential for producing the intermediate A in the first
step. In fact, DMBQ was consumed when PBu3, PPh3, or
PhOPPh2 was used while DMBQ remained when electron-
deficient PhP(OPh)2 or P(OPh)3 was used (Table 1). However,
the desired product was not obtained in the case of PBu3 or
PPh3 without consuming alcohol 1a. This indicated that
alkoxyphosphonium salt C as a key intermediate was not
formed from phosphonium salt B because the attack of alcohol
1a to the positively charged phosphorus atom was retarded. On
the other hand, when PhOPPh2 was used, intermediate C was
A plausible reaction mechanism is shown in Scheme 2:
reaction of phenyl diphenylphosphinite (PhOPPh2) and a
benzoquinone derivative21 such as DMOBQ, DMBQ, or
¹
produced from intermediate B since phenoxide anion (PhO )

K. Kuroda et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 3 (2009)
Table 8. Screening of Azide Compounds
385
Table 7. Screening of Phosphorus(III) Compounds
PX3 (1.1 equiv)
N3CH2CO2Et (1.1 equiv)
PhOPPh2 (1.1 equiv)
Azide (1.1 equiv)
OH
Me
SBtz
Me
OH
SBtz
Me
BtzSH
BtzSH
Ph
1a (1.0 equiv)
Ph
Ph
Me
Ph
1,2-dichloropropane
reflux, 3 h
1,2-dichloropropane
reflux, 3 h
(1.0 equiv)
2a
1a (1.0 equiv)
(1.0 equiv)
2a
Entry
1
Azide
Yield/%a) Entry
Azide
Yield/%a)
Yield
Yield
Entry
PX3
Entry
PX3
/%a)
/%a)
53
4
34
N3
TMS
N3
1
2
3
4
PPh3
PBu3
P(OPh)3
trace
N.D.
34
5
6
7
8
Ph2PCl
11
69
65
R = H
R = Cl
O
R
2
3
67 (81)b)
69 (84)b)
5
6
N.D.
7
N3
N3
Ph
(PhO)2P N3
OPPh2
PhP(OPh)2 58
R = OMe 61
TMSN3
CO2Et
a) Isolated yield.
a) Isolated yield. b) Toluene was used instead of 1,2-
dichloropropane.
was eliminated by the attack of alcohol 1a to the positively
charged phosphorus atom. When ClPPh2 was used as a
reductant, alcohol 1a was converted into the corresponding
These results were similar to the above reactions of using
benzoquinone derivatives.
¹
chloride by the attack of chloride anion (Cl ) as a leaving
Next, various azide compounds were examined to find a
suitable oxidant (Table 8), and a condensation reaction using
trimethylsilylmethyl azide afforded the desired product 2a in
moderate yield (Entry 1). The alkyl azides such as benzyl azide
and ethyl azidoacetate gave 2a in good yields (Entries 2 and 3)
while 1-azidoadamantane, diphenylphosphoryl azide, or tri-
methylsilyl azide did not work well (Entries 4-6). In the cases
of benzyl azide and ethyl azidoacetate, the yields increased up
to 81 and 84%, respectively, by changing solvent from 1,2-
dichloropropane to toluene (Entries 2 and 3).
After a suitable reductant and an oxidant were chosen,
condensation reactions of various alcohols with BtzSH were
tried in order to examine the scope of this reaction under the
optimized conditions (Table 9). The reactions of primary and
secondary alcohols proceeded smoothly to afford the corre-
sponding sulfides in high yields, indicating that this reaction is
tolerant of various functional groups (Entries 1-5). It is noted
that the alcohols 1e and 1t bearing ketone groups were
converted into the corresponding sulfides without any accom-
panying side reactions (Aza-Wittig type reaction) (Entries 1
and 5). The reaction of tertiary alcohol 1j with an ¡-ester group
afforded the corresponding sulfide also in high yield while
yields of tert-alcohols 1k and 1l bearing an ¡-ketone and an
¡-phenyl groups were moderate (Entries 6-8). In the case of
aliphatic substrate 1m, the yield of the desired sulfide markedly
decreased because of elimination reactions that took place to
give undesired olefins (Entry 9).
Next, thioetherification of various chiral alcohols were tried
in order to examine the stereochemistry of this reaction
(Table 10). A reaction of chiral secondary alcohol 1a pro-
ceeded smoothly to afford the corresponding sulfide in
excellent yield with complete inversion of stereochemistry
(Entry 1). Chiral benzylic alcohol 1n and propargylic alcohol
1o also gave the desired products in high yields with high
enantiomeric excesses (Entries 2 and 3). The thioetherification
of sterically hindered (¹)-(l)-menthol (1q) gave the inverted
product in high yield without any other accompanying products
(Entry 4). Further, more hindered tertiary alcohols bearing
¡-ester groups were employed as substrates in order to
study potential application of this reaction to the asymmetric
construction of quaternary carbon (Entries 5-7). Then, a
reaction of chiral tert-alcohol 1r proceeded smoothly to afford
group to activated alcohol 1a while this type side reaction did
not proceed in the case of PhOPPh2. Thus, it is proven that
PhOPPh2 is a suitable reductant which also contains a good
leaving group.
Thus, a new type of oxidation-reduction condensation by the
combined use of PhOPPh2 and benzoquinone derivatives was
found applicable to the thioetherification of various alcohols. In
the case of secondary chiral alcohols, the inverted sulfides were
obtained in good to excellent yields under mild and neutral
conditions. However, the inverted chiral tert-alkyl sulfides were
obtained in moderate yield when chiral tert-alcohols having
¡-ester groups were employed. In order to improve these
yields, our attention was next focused on another type of
oxidation-reduction condensation reaction using organic azides
as oxidants in place of the above-mentioned benzoquinone
derivatives.
Preparation of Alkyl Aryl Sulfides from Alcohols and 2-
Sulfanyl-1,3-benzothiazole (BtzSH) by Oxidation-Reduc-
tion Condensation Using Phenyl Diphenylphosphinite and
Azide Compounds.
A reaction of organic azides22 with
trivalent phosphorus compounds that affords the corresponding
iminophosphoranes (aza-ylides) is known as the Staudinger
reaction.23 Although this iminophosphorane is a versatile
intermediate in organic synthesis,24 there are only few reports25
on the intermolecular dehydration condensation reactions
between alcohols and acidic compounds via this intermediate,
iminophosphorane, which are considered to be similar species
of an betain intermediate A (Scheme 2). Thus, the use of azide
compounds14d,14e instead of benzoquinone derivatives was tried
next in order to determine if this iminophosphorane works as
the intermediate in oxidation-reduction condensation.
In order to find the most suitable reductant, effects of
phosphorus(III) compounds were first examined by condensa-
tion reaction of 4-phenylbutan-2-ol (1a) and BtzSH in the
presence of ethyl azidoacetate (Table 7). Then, it was shown
that the desired sulfide 2a was not obtained when PPh3 and
PBu3 were used (Entries 1 and 2) while it was formed when
P(OPh)3, PhP(OPh)2, and Ph2PCl were used (Entries 3-5). In
the case when aryl diphenylphosphinites were employed, the
yield of 2a markedly increased (Entries 6-8) and phenyl
diphenylphosphinite (PhOPPh2) was among the best (Entry 6).

386
Bull. Chem. Soc. Jpn. Vol. 82, No. 3 (2009)
Synthesis of Alkyl Aryl Sulfides
Table 9. Thioetherification of Various Alcohols
and the corresponding sulfides were obtained in high yields
(Entries 6-9). When thiobenzoic acid (pKa 5.3 in DMSO) was
used, the yield of the desired product was poor in spite of
sufficient acidity. These results are similar to those that used
benzoquinone derivatives except in the case when benzenethiol
derivatives were employed as sulfur nucleophiles.
PhOPPh2 (1.5 equiv)
N3CH2CO2Et (1.5 equiv)
ROH
BtzSH
R
SBtz
Toluene, 40 °C, 15 h
1 (1.0 equiv)
(1.1 equiv)
2
Yield
/%a)
Entry
ROH
1
Product
2
A plausible reaction mechanism is shown in Scheme 3: the
Staudinger reaction of phenyl diphenylphosphinite (PhOPPh2)
and an azide compound26 gives initially an iminophosphorane,
and deprotonation of BtzSH by the iminophosphorane results
in the formation of intermediate A. A subsequent nucleophilic
attack of alcohol to the positively charged phosphorus atom
leads to formation of intermediate B and the following
Ph
Ph
OH
SBtz
1
2
1e
2e
82
91
O
O
OH
SBtz
1f
2f
TBSO
TBSO
OH
SBtz
3
1g
1h
1t
2g
2h
2t
95
95
94
N
N
¹
nucleophilic attack of thiolate anion (BtzS ) to the carbon
H
H
atom adjacent to an oxygen atom of alkoxy group in SN2
fashion gives the inverted sulfide. The reason why PhOPPh2
among phosphorus compounds gave the best result is consid-
ered as follows. In the first step, most phosphorus compounds
gave the corresponding iminophosphoranes quantitatively
except for electron-deficient P(OPh)3 (Table 7). In the second
step, the basicity of iminophosphorane is essential for
formation of intermediate A. Since the basicity of iminophos-
phorane prepared from electron-deficient PhP(OPh)2 or
P(OPh)3 is lower than that prepared from PhOPPh2, the
reaction rate of formation of intermediate A in the case of
PhP(OPh)2 or P(OPh)3 is slower than that in the case of
PhOPPh2, whose differences affect the yield of the desired
product. On the other hand, the desired product was not
obtained in the case of PBu3 or PPh3 without consuming
alcohol 1a. This indicated that alkoxyphosphonium salt B as a
key intermediate was not formed from phosphonium salt A as
well as in reactions using benzoquinone derivatives. When
ClPPh2 was used as a reductant, alcohol 1a was converted into
the corresponding chloride. Thus, it is proven that PhOPPh2 is a
suitable reductant which also contains a good leaving group.
Thus, this type of oxidation-reduction condensation by the
combined use of PhOPPh2 and azide compounds was success-
fully applied to the thioetherification of various alcohols
including tertiary alcohol. Secondary and tertiary alcohols were
converted into the corresponding sulfides in good to excellent
yields with almost complete inversion of their configuration
under mild and neutral conditions. In most cases, these
reactions that used azides as oxidants have advantages over
the reactions using benzoquinone derivatives.27
Finally, in order to confirm the utility of the above results,
condensation of chiral tertiary alcohols 1r and 1s with BtzSH
were further examined with other oxidation-reduction systems
(Table 12). Interestingly, the PhOPPh2-DEAD system afforded
the desired sulfides in moderate yields with clean inversion of
stereochemistry both using alcohols 1r and 1s while the PPh3-
DEAD system (Mitsunobu conditions) did not give the desired
products. By comparing various oxidation-reduction systems,
the yields of products 2r and 2s were found to increase in
the order of PhOPPh2-N3CH2CO2Et > PhOPPh2-DMBQ >
PhOPPh2-DEAD > PPh3-DEAD systems. Since the desired
products were not obtained under any oxidation-reduction
system when PPh3 was used instead of PhOPPh2, it is proven
that PhOPPh2 is a very useful reductant which also contains a
good leaving PhO group, a proton acceptor.
OH
SBtz
4
BocHN
BocHN
Ph
OH
Ph
SBtz
Ph
5b)
Ph
O
O
Me OH
Me SBtz
6b),c)
7b),d)
8b),d)
9b),d)
1j
2j
2k
2l
94
42
53
Me
Ph
CO2Me
Me OH
Me
Me
CO2Me
Me SBtz
Ph
1k
Me
O
O
Me OH
Ph Me
Me OH
Me
Me SBtz
1l
Ph
Me
Me SBtz
1m
2m 17
Ph
Ph
Me
a) Isolated yield. b) The reaction time was 24 h. c) The reaction
was carried out by using BtzSH (2.0 equiv), PhOPPh2 (2.0
equiv), and N3CH2CO2Et (2.0 equiv). d) The reaction was
carried out by using BtzSH (4.0 equiv), PhOPPh2 (4.0 equiv),
and N3CH2CO2Et (4.0 equiv).
the corresponding sulfide in good yield with complete
inversion of stereochemistry (Entry 5). Similarly, chiral ben-
zylic alcohol 1s gave the desired product in high yield with
excellent enantiomeric excess (Entry 6). Also, thioetherifica-
tion of chiral propargylic alcohol 1u gave the inverted product
in high yield (Entry 7). On the other hand, the reaction of (R)-
terpinen-4-ol (1v) under the above conditions did not proceed
and it was recovered, which is probably because its bulky
isopropyl group interferes with the attack of 1v to the positively
charged phosphorus atom (Entry 8).
Next, reactions of various arenethiols or thiobenzoic acid
with tertiary alcohol 1j were examined in order to extend the
scope of this reaction as well as reactions that used benzoqui-
none derivatives (see Table 11 and Table 6). When benzene-
thiol derivatives were used as sulfur nucleophiles, the yields of
the products increased in the following order: 4-nitrobenzene-
thiol (pKa 5.11 in EtOH/H2O, 5.5 in DMSO) > benzenethiol
(pKa 7.76 in EtOH/H2O, 10.3 in DMSO) > 4-methoxyben-
zenethiol (pKa 7.99 in EtOH/H2O, 11.2 in DMSO) (Entries
1-3). These results indicate that the yields of the condensation
reactions are influenced by the pKa values of the nucleophiles.
Also, the reactivity of 5-nitro-2-sulfanylpyridine was shown to
be higher than that of 2-sulfanylpyridine (Entries 4 and 5).
Reactions of various heteroarene thiols were further examined

K. Kuroda et al.
Table 10. Thioetherification of Various Chiral Alcohols
Bull. Chem. Soc. Jpn. Vol. 82, No. 3 (2009)
387
PhOPPh2 (1.5 equiv)
N3CH2CO2Et (1.5 equiv)
R1 OH
R1 SBtz
R2 R3
BtzSH
R2
R3
Toluene
1 (1.0 equiv)
(1.1 equiv)
2
Yield/%a)
(%ee)b)
Entry
1
ROH
1 (%ee)
Temp, Time
40 °C, 24 h
rt, 12 h
Product
2
OH
SBtz
Me
99
(>99)
1a (>99)
1n (>99)
2a
2n
Ph
Me
Ph
OH
Me
SBtz
83
(97)
2c)
Ph
OH
Ph
SBtz
Me
89
(98)
3c)
4
1o (98)
rt, 24 h
2o
2q
3
3
OH
SBtz
1q
80 °C, 6 h
85
Me OH
Et CO2Bn
Me OH
Ph CO2Me
Me OH
Me SBtz
76
(>99)
5d)
6d)
1r (>99)
1s (>99)
40 °C, 48 h
40 °C, 48 h
2r
2s
Et
CO2Bn
Me SBtz
90
(99)
Ph
Me SBtz
CO2Et
CO2Me
87
(92)
7c),d)
1u (92)
27 °C, 48 h
40 °C, 48 h
2u
2v
CO2Et
Ph
Ph
OH
SBtz
8
1v
N.R.
a) Isolated yield. b) Determined by HPLC analysis. c) The solution of PhOPPh2 and ethyl azidoacetate was
stirred at 80 °C for 20 min, followed by addition of alcohol and BtzSH at rt. d) The reaction was carried out
by using BtzSH (4.0 equiv), PhOPPh2 (4.0 equiv), and ethyl azidoacetate (4.0 equiv).
Table 11. Condensation of Tertiary Alcohol 1j with Various ArSH
PhOPPh2 (2.0 equiv)
N3CH2CO2Et (2.0 equiv)
Me OH
Me CO2Me
Me SAr
Me CO2Me
ArSH
Toluene, 40 °C, 24 h
1j (1.0 equiv)
(2.0 equiv)
3
Entry
1
ArSH
Product 3 Yield/%a) Entry
ArSH
Product 3 Yield/%a)
N
N
N
HS
3a
44
6
3f
83
HS
N
Me
N
2
3
4
5
3b
3c
3d
3e
85
19
72
97
7
8
HS
HS
2j
3g
3h
3i
94
91
89
34
HS
HS
NO2
S
N
OMe
S
N
NO2
N
9
HS
HS
HS
HS
O
O
N
10
NO2
Ph
a) Isolated yield.
applied to the thioetherification of various alcohols including
tertiary alcohol, and it was shown that the reaction using azides
as oxidants is advantageous over that using benzoquinone
derivatives in most cases. It is noted that chiral sec- or tert-alkyl
sulfides were formed from the corresponding chiral alcohols
Conclusion
A new type of oxidation-reduction condensation by the
combined use of PhOPPh2 with azide compounds or benzo-
quinone derivatives was established. This reaction system was

388
Bull. Chem. Soc. Jpn. Vol. 82, No. 3 (2009)
Synthesis of Alkyl Aryl Sulfides
otherwise noted. Dry solvents (1,2-dichloropropane) were prepared
by distillation over appropriate drying agents. Dehydrated solvents
(Toluene, THF, Et2O, CHCl3, CH2Cl2, and EtOAc) were purchased
from KANTO KAGAKU. Dehydrated solvents (CH3CN) were
purchased from KOKUSAN KAGAKU. Arenethiols, alcohols,
PPh3, PBu3, P(OPh)3, ClPPh2, Et3N, DMAP, benzoquinone
derivatives, TMSCH2N3, DPPA, TMSN3, and DEAD were
purchased from Tokyo Kasei Kogyo (TCI) unless otherwise noted.
N3CH2CO2Et and BnN3 were purchased from Wako. (S)-4-
Phenylbutan-2-ol, 4-(tert-butyldimethylsilyl)oxy-1-butanol, and
1-azidoadamantane were purchased from Aldrich.
Ph Ph
PhO P N R
Ph Ph
PhO P N R
H
SBtz
PhOPPh2 RN3
N2
Iminophosphorane
Ph Ph
PhO P N R
Ph
P
H
R1 SBtz
Ph
R1
R2
O
H
N R
H
R1 OH
O
Ph2P NR
R2
R3
SBtz PhOH
R3
R2
R3
SBtz
'' Inversion''
A
B
Scheme 3.
Procedure for the Preparation of Chiral Tertiary Alchohols.
(S)-Benzyl 2-hydroxy-2-methylbutyrate (Table 5, Entry 6) and (S)-
methyl ¡-phenyllactate (Table 5, Entry 7) were prepared following
a literature procedure.16a Ethyl (S)-2-hydroxyl-2-methyl-4-phenyl-
3-butynoate (Table 10, Entry 7) was prepared from ethyl pyruvate
and phenylacetylene according to Jiang’s procedure for the
preparation of the R enantiomer.28
Table 12. Reaction of Tertialy Alcohols with BtzSH
Reductant (4.0 equiv)
R1 OH
R1 SBtz
R2 R3
Oxidant (4.0 equiv)
BtzSH
R2
R3
Toluene, 40 °C, 48 h
1 (1.0 equiv)
(4.0 equiv)
2
Oxidation-Reduction system (Yield/% (%ee))
General Procedure for the Preparation of Aryl Diphenyl-
phosphinite (ArOPPh2). A typical procedure for the preparation
of aryl diphenylphosphinites is described for phenyl diphenyl-
phosphinite (PhOPPh2). To a stirred solution of phenol (1.88 g,
20 mmol) and DMAP (489 mg, 4 mmol) in dry THF (50 mL) were
added Et3N (3.33 mL, 24 mmol) followed by ClPPh2 (4.04 mL,
22 mmol) under argon atmosphere. After stirring at rt for 2 h, the
resulting white slurry was concentrated by a rotary evaporator.
After dilution of the residue with hexane/ethyl acetate (v/v = 9/1,
ca. 160 mL, HPLC grade), the mixture was filtered through a pad
of alumina (activated, 300 mesh; purchased from Wako Pure
Chemical Industries, Ltd.) and Celite. The filtrate was concentrated
under reduced pressure to give phenyl diphenylphosphinite (5.40 g,
97%), which is pure enough without further purification. PhOPPh2
was similarly synthesized in the absence of DMAP.
Phenyl Diphenylphosphinite (PhOPPh2): Colorless oil; IR
(neat, cm¹1): 1488, 1212, 863, 741, 721, 688; 1H NMR (270 MHz,
CDCl3): ¤ 7.64-7.47 (m, 4H), 7.40-6.90 (m, 11H); 13C NMR
(68 MHz, CDCl3): ¤ 157.1 (d, J = 10.1 Hz), 140.7 (d, J = 16.8
Hz), 130.4 (d, J = 22.4 Hz), 129.6, 129.4, 128.4 (d, J = 7.3 Hz),
122.4, 118.7 (d, J = 10.6 Hz); HRMS (ESI) Calcd for C18H16OP:
[M + H]+ 279.0939. Found: 279.0920.
ROH
1
PPh3 PhOPPh2 PhOPPh2
DEAD DEAD DMBQ
PhOPPh2
N3CH2CO2Et
Me OH
1r trace 43 (>99) 55 (>99)a)
1s N.D. 53 (>99) 56 (>99)a)
76 (>99)
Et
Me OH
Ph CO2Me
CO2Bn
90 (99)
a) The reaction was carried out at rt for 24 h.
with almost complete inversion of configuration under mild
and neutral conditions. Since the chiral tert-alkyl Btz sulfide
obtained was converted to the corresponding chiral tert-thiol in
high yield on treatment with LiAlH4, a concise method for the
chiral thiols from the corresponding alcohols was established.
This is the first example of the stereospecific syntheses of
inverted chiral tert-thiol derivatives formed directly from chiral
tert-alcohols by an SN2 displacement.
Experimental
General. All melting points were determined on a Yanagimoto
micro melting point apparatus (Yanaco MP-S3) and remain
uncorrected. Infrared (IR) spectra were recorded on a SensIR
Technologies TravelIR portable FT-IR spectrometer. 1H NMR
spectra were recorded on a JEOL JNM-EX270L (270 MHz)
spectrometer; chemical shifts (¤) are reported in parts per million
relative to tetramethylsilane. Splitting patterns are designated as s,
singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad.
13C NMR spectra were recorded on a EX270L (68 MHz) spec-
trometer with complete proton decoupling. Chemical shifts are
reported in parts per million relative to tetramethylsilane with
the solvent resonance as the internal standard (CDCl3; ¤ 77.0).
Carbon-31P coupling constants are reported when possible. High-
resolution mass spectral analysis (HRMS) was carried out on a
Bruker-Daltonics micrOTOF focus instrument. The optical rota-
tions were measured with a JASCO P-1020 polarimeter. High-
performance liquid chromatography (HPLC) was carried out using
a Hitachi LC-Organizer, L-4000UV Detecter, L-6200 Intelligent
Pump, and D-2500 Chromato-Integrator. Analytical TLC was
performed on Merck preparative TLC plates (silica gel 60 GF254,
0.25 mm). Preparative thin-layer chromatography (PTLC) was
carried out on silica gel Wakogel B-5F. All reactions were carried
out under an argon atmosphere in dried glassware, unless
2-Chlorophenyl Diphenylphosphinite (2-ClC6H4OPPh2):
Colorless oil; IR (neat, cm¹1): 1475, 1232, 870, 736, 692, 673;
1H NMR (270 MHz, CDCl3): ¤ 7.73-7.60 (m, 4H), 7.46-7.32 (m,
7H), 7.22-7.06 (m, 2H), 6.97-6.88 (m, 1H); 13C NMR (68 MHz,
CDCl3): ¤ 152.8 (d, J = 10.1 Hz), 140.4 (d, J = 17.9 Hz), 130.4 (d,
J = 22.9 Hz), 130.2, 129.8, 128.4 (d, J = 7.3 Hz), 127.5, 125.1 (d,
J = 2.8 Hz), 123.1, 119.2 (d, J = 17.3 Hz); HRMS (ESI) Calcd for
C18H14OPClNa: [M + Na]+ 335.0369. Found: 335.0363.
2-Methoxyphenyl Diphenylphosphinite (2-MeOC6H4O-
PPh2): Colorless oil; IR (neat, cm¹1): 1498, 1254, 870, 739,
693; 1H NMR (270 MHz, CDCl3): ¤ 7.70-7.57 (m, 4H), 7.44-7.30
(m, 6H), 7.07-6.76 (m, 4H), 3.79 (s, 3H); 13C NMR (68 MHz,
CDCl3): ¤ 151.0 (d, J = 3.4 Hz), 141.5 (d, J = 17.9 Hz), 130.5 (d,
J = 22.4 Hz), 129.4, 129.1, 128.2 (d, J = 6.7 Hz), 123.4 (d, J =
1.7 Hz), 120.7, 120.2 (d, J = 11.7 Hz), 112.5, 55.9; HRMS (ESI)
Calcd for C19H18O2P: [M + H]+ 309.1044. Found: 309.1054.
Diphenyl Phenylphosphonite (PhP(OPh)2).
To a stirred
solution of phenol (3.76 g, 40 mmol) and DMAP (489 mg, 4 mmol)
in dry THF (60 mL) were added Et3N (6.13 mL, 44 mmol)
followed by Cl2PPh (2.71 mL, 20 mmol) under argon atmosphere.
After stirring at rt for 4 h, the resulting white slurry was
concentrated by a rotary evaporator. After dilution of the residue

K. Kuroda et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 3 (2009)
389
with hexane/ethyl acetate (v/v = 9/1, ca. 200 mL, HPLC grade),
the mixture was filtered through a pad of alumina (activated, 300
mesh; purchased from Wako Pure Chemical Industries, Ltd.) and
Celite. The filtrate was concentrated under reduced pressure to give
diphenyl phenylphosphonite (4.88 g, 83%). Colorless oil; IR (neat,
cm¹1): 1484, 1217, 1191, 855, 760, 749, 720, 687; 1H NMR
(270 MHz, CDCl3): ¤ 7.85-7.74 (m, 2H), 7.51-7.42 (m, 3H), 7.30-
7.18 (m, 4H), 7.13-7.00 (s, 6H); 13C NMR (68 MHz, CDCl3): ¤
155.0 (d, J = 5.6 Hz), 139.8 (d, J = 14.5 Hz), 130.9, 129.6 (d,
J = 23.5 Hz), 129.5, 128.3 (d, J = 6.1 Hz), 123.5 (d, J = 1.1 Hz),
119.9 (d, J = 8.4 Hz); HRMS (ESI) Calcd for C18H15O2PNa:
[M + Na]+ 317.0707. Found: 317.0734.
General Procedure for Condensation of Alcohols with
BtzSH by Using PhOPPh2 and Benzoquinone Derivatives.
A typical procedure for the preparation of alkyl aryl sulfides is
described for sulfide 2a. To a solution of PhOPPh2 (125.2 mg,
0.45 mmol) and (S)-4-phenylbutan-2-ol (1a) (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 afford the correspond-
ing sulfide 2a (89.2 mg, 99%).
General Procedure for Condensation of Alcohols with
BtzSH by Using PhOPPh2 and Azide Compounds. A typical
procedure for the preparation of alkyl aryl sulfides is described for
sulfide 2s. To a solution of PhOPPh2 (222.6 mg, 0.80 mmol) and
chiral alcohol 1s (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 argon atmosphere.
The reaction mixture was stirred at 40 °C for 48 h and the crude
product was purified by preparative TLC to afford the correspond-
ing sulfide 2s (58.9 mg, 90%).
724, 705, 664; 1H NMR (270 MHz, CDCl3): ¤ 7.88 (d, J = 8.1 Hz,
1H), 7.73 (d, J = 7.9 Hz, 1H), 7.50-7.23 (m, 4H), 6.45 (s, 1H),
4.42 (s, 2H); 13C NMR (68 MHz, CDCl3): ¤ 165.9, 152.9, 143.2,
140.9, 135.1, 125.9, 124.2, 121.4, 120.9, 120.1, 110.8, 27.9;
HRMS (ESI) Calcd for C12H9NOS2Na: [M + Na]+ 270.0023.
Found: 270.0023.
2-(Phenacylsulfanyl)-1,3-benzothiazole (2e): Yellow solid;
mp 110-111 °C; IR (neat, cm¹1): 1678, 1426, 1288, 1191, 995,
750, 688; 1H NMR (270 MHz, CDCl3): ¤ 8.05 (d, J = 7.3 Hz, 2H),
7.82-7.23 (m, 7H), 4.95 (s, 2H); 13C NMR (68 MHz, CDCl3): ¤
192.7, 165.0, 152.7, 135.3, 133.7, 128.6, 128.4, 125.9, 124.3,
121.3, 120.9, 41.0; HRMS (ESI) Calcd for C15H11NOS2Na:
[M + Na]+ 308.0180. Found: 308.0166.
2-[4-(tert-Butyldimethylsilyloxy)butylsulfanyl]-1,3-benzothia-
zole (2f): Colorless oil; IR (neat, cm¹1): 1460, 1427, 1099, 993,
835, 774, 754, 724, 706; 1H NMR (270 MHz, CDCl3): ¤ 7.85
(d, J = 8.1 Hz, 1H), 7.74 (d, J = 7.9 Hz, 1H), 7.43-7.37 (m, 1H),
7.31-7.25 (m, 1H), 3.66 (t, J = 6.1 Hz, 2H), 3.38 (d, J = 7.3 Hz,
2H), 1.96-1.85 (m, 2H), 1.75-1.65 (m, 2H), 0.88 (s, 9H), 0.05 (s,
6H); 13C NMR (68 MHz, CDCl3): ¤ 167.0, 153.1, 135.0, 125.8,
124.0, 121.3, 120.8, 62.4, 33.5, 31.8, 26.0, 25.9, 18.4, ¹5.2;
HRMS (ESI) Calcd for C17H27NOS2SiNa: [M + Na]+ 376.1201.
Found: 376.1211.
2-[2-(Indol-2-yl)ethylsulfanyl]-1,3-benzothiazole (2g): Yel-
low solid; mp 134-136 °C; IR (neat, cm¹1): 3226, 1739, 1455,
1423, 1220, 1004, 758, 739, 726, 668; 1H NMR (270 MHz,
CDCl3): ¤ 8.07 (br, 1H), 7.89 (d, J = 7.9 Hz, 1H), 7.75-7.72 (m,
2H), 7.50-7.00 (m, 6H), 3.66 (t, J = 7.3 Hz, 2H), 3.29 (t, J =
7.3 Hz, 2H); 13C NMR (68 MHz, CDCl3): ¤ 166.9, 153.2, 136.1,
135.1, 127.0, 125.9, 124.0, 122.1, 122.0, 121.3, 120.9, 119.4,
118.8, 114.0, 111.1, 34.2, 25.6; HRMS (ESI) Calcd for
C17H14N2S2Na: [M + Na]+ 333.0496. Found: 333.0503.
tert-Butyl [2-(1,3-Benzothiazol-2-ylsulfanyl)ethyl]carbamate
(2h): White needles; mp 103-105 °C; IR (neat, cm¹1): 3372,
1682, 1524, 1453, 1424, 1265, 1251, 1240, 1167, 1140, 1002, 751,
723; 1H NMR (270 MHz, CDCl3): ¤ 7.84 (d, J = 8.1 Hz, 1H), 7.73
(d, J = 7.7 Hz, 1H), 7.44-4.24 (m, 2H), 5.34 (br, 1H), 3.62-3.42
(m, 4H), 1.43 (s, 9H); 13C NMR (68 MHz, CDCl3): ¤ 166.0, 155.6,
152.9, 135.2, 125.9, 124.2, 121.4, 120.8, 79.4, 40.5, 33.6, 28.4;
HRMS (ESI) Calcd for C14H18N2O2S2Na: [M + H]+ 333.0707.
Found: 333.0705.
(R)-2-(1-Methyl-3-phenylpropylsulfanyl)-1,3-benzothiazole
(2a): Colorless oil; >99% ee; The ee value was determined by
chiral HPLC analysis (DAICEL CHIRALCEL OD-H column,
hexane/i-PrOH = 250/1, flow rate = 1.0 mL min¹1): tR = 15.0
38
(S), 26.2 min (R); ½¡ꢀD = +43.0 (c 0.79, CHCl3); IR (neat,
cm¹1): 1454, 1425, 989, 752, 726, 697; 1H NMR (270 MHz,
CDCl3): ¤ 7.87 (d, J = 8.1 Hz, 1H), 7.72 (d, J = 7.9 Hz, 1H),
7.42-7.14 (m, 7H), 4.02-3.95 (m, 1H), 2.81 (d, J = 8.1 Hz, 2H),
2.19-1.93 (m, 2H), 1.54 (d, J = 6.9 Hz, 3H); 13C NMR (68 MHz,
CDCl3): ¤ 166.0, 153.2, 141.1, 135.1, 128.3, 125.9 (©2), 124.1,
121.4, 120.8, 43.9, 38.5, 33.2, 21.6; HRMS (ESI) Calcd for
C17H17NS2Na: [M + Na]+ 322.0700. Found: 320.0699.
2-(Cyclopentylsulfanyl)-1,3-benzothiazole (2i):
Colorless
oil; IR (neat, cm¹1): 1454, 1424, 989, 753, 724; 1H NMR (270
MHz, CDCl3): ¤ 7.87 (d, J = 8.1 Hz, 1H), 7.74 (d, J = 7.9 Hz,
1H), 7.43-7.24 (m, 2H), 4.16-4.06 (m, 1H), 2.37-2.18 (m, 2H),
1.90-1.58 (m, 6H); 13C NMR (68 MHz, CDCl3): ¤ 167.3, 153.2,
135.0, 125.8, 123.9, 121.4, 120.7, 46.6, 33.8, 24.9; HRMS (ESI)
Calcd for C12H13NS2Na: [M + Na]+ 258.0387. Found: 258.0374.
Methyl 2-[(1,3-Benzothiazol-2-yl)sulfanyl]-2-methylpropio-
2-(Benzylsulfanyl)-1,3-benzothiazole (2b): Colorless oil; IR
(neat, cm¹1): 1454, 1425, 992, 753, 724, 696, 668; 1H NMR
(270 MHz, CDCl3): ¤ 7.88 (d, J = 8.1 Hz, 1H), 7.70 (d, J = 7.9
Hz, 1H), 7.50-7.19 (m, 7H), 4.58 (s, 2H); 13C NMR (68 MHz,
CDCl3): ¤ 166.2, 152.9, 136.0, 135.1, 129.0, 128.5, 127.6, 125.9,
124.1, 121.4, 120.8, 37.7; HRMS (ESI) Calcd for C14H11NS2Na:
[M + Na]+ 280.0231. Found: 280.0225.
2-[(E)-3-Phenyl-2-propenylsulfanyl]-1,3-benzothiazole (2c):
White solid; mp 61-63 °C; IR (neat, cm¹1): 1453, 1422, 993,
967, 748, 726, 703, 689; 1H NMR (270 MHz, CDCl3): ¤ 7.88
(d, J = 8.2 Hz, 1H), 7.72 (d, J = 7.9 Hz, 1H), 7.43-7.15 (m, 7H),
6.67 (d, J = 15.7 Hz, 1H), 6.35 (dt, J = 15.7, 7.3 Hz, 1H), 4.14
(d, J = 7.3 Hz, 2H); 13C NMR (68 MHz, CDCl3): ¤ 165.9, 152.9,
136.1, 135.1, 134.1, 128.4, 127.7, 126.3, 125.9, 124.1, 123.3,
121.4, 120.8, 36.0; HRMS (ESI) Calcd for C16H13NS2Na:
[M + Na]+ 306.0387. Found: 306.0385.
nate (2j):
Spectral data were consistent with these of the
literature.16a Colorless oil; IR (neat, cm¹1): 1731, 1457, 1427,
1
1264, 1153, 1122, 986, 756, 727; H NMR (270 MHz, CDCl3): ¤
7.93 (d, J = 7.9 Hz, 1H), 7.77 (d, J = 7.9 Hz, 1H), 7.46-7.26 (m,
2H), 3.75 (s, 3H), 1.74 (s, 6H); 13C NMR (68 MHz, CDCl3): ¤
173.6, 161.7, 153.2, 136.3, 126.0, 124.9, 122.5, 120.9, 53.9, 52.9,
26.4.
2-[(1,3-Benzothiazol-2-yl)sulfanyl]-2-methylpropiophenone
(2k): Spectral data are consistent with those of the literature.16a
Pale yellow oil; IR (neat, cm¹1): 1677, 1456, 1426, 1254, 989,
973, 756, 725, 705, 692, 661; 1H NMR (270 MHz, CDCl3): ¤ 8.09
(d, J = 7.9 Hz, 2H), 7.88 (d, J = 7.9 Hz, 1H), 7.70 (d, J = 7.9 Hz,
1H), 7.53-7.23 (m, 5H), 1.86 (s, 6H); 13C NMR (68 MHz, CDCl3):
2-(3-Furylmethylsulfanyl)-1,3-benzothiazole (2d):
Pale
yellow oil; IR (neat, cm¹1): 1456, 1425, 1018, 993, 872, 753,

390
Bull. Chem. Soc. Jpn. Vol. 82, No. 3 (2009)
Synthesis of Alkyl Aryl Sulfides
¤ 200.3, 161.2, 153.0, 136.6, 136.2, 131.6, 128.9, 127.8, 126.0,
124.8, 122.4, 120.8, 58.1, 27.4.
30.7, 27.7, 27.0, 22.1, 21.1, 20.9; HRMS (ESI) Calcd for
C17H24NS2: [M + H]+ 306.1315. Found: 306.1346.
2-[(1-Methyl-1-phenylethyl)sulfanyl]-1,3-benzothiazole (2l):
Spectral data are consistent with those of the literature.16a Colorless
oil; IR (neat, cm¹1): 1452, 1424, 978, 755, 727, 695, 671; 1H NMR
(270 MHz, CDCl3): ¤ 7.94 (d, J = 8.1 Hz, 1H), 7.71-7.57 (m, 3H),
7.45-7.23 (m, 5H), 1.96 (s, 6H); 13C NMR (68 MHz, CDCl3): ¤
163.3, 152.8, 144.8, 136.4, 128.3, 127.2, 126.7, 125.8, 124.7,
122.5, 120.7, 54.8, 30.4.
2-[(1,1-Dimethyl-3-phenylpropyl)sulfanyl]-1,3-benzothiazole
(2m): Spectral data are consistent with those of the literature.16a
Colorless oil; IR (neat, cm¹1): 1453, 1425, 978, 754, 726, 697,
671; 1H NMR (270 MHz, CDCl3): ¤ 7.97 (d, J = 7.9 Hz, 1H), 7.79
(d, J = 7.7 Hz, 1H), 7.50-7.10 (m, 7H), 2.91-2.75 (m, 2H), 2.23-
2.07 (m, 2H), 1.61 (s, 6H); 13C NMR (68 MHz, CDCl3): ¤ 163.0,
153.7, 142.0, 136.3, 128.4, 128.3, 125.9, 125.7, 124.8, 122.5,
120.8, 54.3, 44.5, 31.6, 29.1.
(R)-Benzyl 2-[(1,3-Benzothiazol-2-yl)sulfanyl]-2-methylbuty-
rate (2r):
Spectral data are consistent with those of the
literature.16a Colorless oil; >99% ee; the ee value was determined
by chiral HPLC analysis (DAICEL CHIRALCEL OD-H column,
hexane/i-PrOH = 700/1, flow rate = 1.0 mL min¹1): tR = 67.4
38
(S), 74.6 min (R); ½¡ꢀD = +15.0 (c 1.25, CHCl3); IR (neat,
cm¹1): 1728, 1454, 1427, 1228, 1144, 1121, 987, 754, 727, 696,
676; 1H NMR (270 MHz, CDCl3): ¤ 7.85 (d, J = 7.9 Hz, 1H), 7.74
(d, J = 7.7 Hz, 1H), 7.44-7.18 (m, 7H), 5.17 (m, 2H), 2.24-1.95
(m, 2H), 1.76 (s, 3H), 1.01 (t, J = 7.4 Hz, 3H); 13C NMR (68 MHz,
CDCl3): ¤ 172.4, 161.7, 153.2, 136.3, 135.4, 128.3, 127.9, 125.9,
124.8, 122.5, 120.8, 67.4, 59.0, 31.8, 23.1, 9.3.
(R)-Methyl 2-[(1,3-Benzothiazol-2-yl)sulfanyl]-2-phenylpro-
pionate (2s):
Spectral data are consistent with those of the
literature.16a Colorless solid; mp 45-47; 99% ee; The ee value was
determined by chiral HPLC analysis (DAICEL CHIRALCEL OD-
H column, hexane/i-PrOH = 700/1, flow rate = 1.0 mL min¹1):
(S)-2-(1-Phenylethylsulfanyl)-1,3-benzothiazole (2n): Color-
less oil; 97% ee; the ee value was determined by chiral
HPLC analysis (DAICEL CHIRALCEL OD-H column, hexane/
i-PrOH = 250/1, flow rate = 1.0 mL min¹1): tR = 11.9 (S), 34.6
27
tR = 68.1 (S), 75.3 min (R); ½¡ꢀD = ¹88.4 (c 1.05, CHCl3); IR
(neat, cm¹1): 1730, 1453, 1427, 1237, 984, 755, 726, 694;
1H NMR (270 MHz, CDCl3): ¤ 7.92 (d, J = 8.2 Hz, 1H), 7.73 (d,
J = 7.9 Hz, 1H), 7.63-7.55 (m, 2H), 7.47-7.27 (m, 5H), 3.79 (s,
3H), 2.24 (s, 3H); 13C NMR (68 MHz, CDCl3): ¤ 172.0, 162.5,
152.9, 138.7, 136.1, 128.7, 128.4, 126.8, 125.9, 124.8, 122.4,
120.9, 61.6, 53.4, 25.8.
38
min (R); ½¡ꢀD = ¹337.6 (c 0.71, CHCl3); IR (neat, cm¹1): 1454,
1424, 989, 754, 725, 695, 658; 1H NMR (270 MHz, CDCl3): ¤
7.89 (d, J = 8.1 Hz, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.49-7.21 (m,
7H), 5.15 (q, J = 7.1 Hz, 1H), 1.84 (d, J = 7.1 Hz, 3H); 13C NMR
(68 MHz, CDCl3): ¤ 165.6, 153.0, 141.6, 135.2, 128.5, 127.6,
127.2, 125.8, 124.2, 121.5, 120.8, 47.5, 22.7; HRMS (ESI) Calcd
for C15H13NS2Na: [M + Na]+ 294.0387. Found: 294.0390.
(R)-2-(1-Ethynylhexylsulfanyl)-1,3-benzothiazole (2o): Col-
orless oil; 98% ee; the ee value was determined by chiral
HPLC analysis (DAICEL CHIRALCEL OD-H column, hexane/
i-PrOH = 250/1, flow rate = 1.0 mL min¹1): tR = 11.7 (S), 22.4
2-[(1,3-Benzothiazol-2-yl)sulfanyl]-1,2-diphenylethanone (2t):
Yellow solid; mp 105-107 °C; IR (neat, cm¹1): 1692, 1426, 1197,
998, 748, 740, 725, 690, 680; 1H NMR (270 MHz, CDCl3): ¤ 8.05
(d, J = 7.3 Hz, 2H), 7.75-7.15 (m, 12H), 6.95 (s, 1H); 13C NMR
(68 MHz, CDCl3): ¤ 194.0, 164.7, 152.6, 135.4 (©2), 134.5, 133.2,
129.0, 128.9, 128.5, 125.7, 124.2, 121.3, 120.9, 58.2; HRMS (ESI)
Calcd for C21H15NOS2Na: [M + Na]+ 384.0493. Found:
384.0487.
15
min (R); ½¡ꢀD = +166.5 (c 1.02, CHCl3); IR (neat, cm¹1): 3298,
1
2927, 1458, 1426, 991, 754, 725; H NMR (270 MHz, CDCl3): ¤
7.90 (d, J = 7.9 Hz, 1H), 7.76 (d, J = 7.9 Hz, 1H), 7.46-7.24 (m,
2H), 4.73-4.67 (m, 1H), 2.40 (d, J = 2.3 Hz, 1H), 2.07-1.86 (m,
2H), 1.69-1.53 (m, 2H), 1.43-1.25 (m, 4H), 0.97-0.82 (m, 3H);
13C NMR (68 MHz, CDCl3): ¤ 164.2, 152.9, 135.4, 125.9, 124.4,
121.8, 120.9, 82.3, 72.7, 38.0, 35.2, 31.1, 26.6, 22.5, 14.1; HRMS
(ESI) Calcd for C15H17NS2Na: [M + Na]+ 298.0700. Found:
298.0696.
(R)-Ethyl 2-[(1,3-Benzothiazol-2-yl)sulfanyl]-2-methyl-4-
phenylbut-3-ynoate (2u): Yellow oil; 92% ee; the ee value
was determined by chiral HPLC analysis (DAICEL CHIRALPAK
AS-H column, hexane/i-PrOH = 1000/1, flow rate = 0.5
37
mL min¹1): tR = 46.1 (S), 51.1 min (R); ½¡ꢀD = +132.0 (c 1.02,
CHCl3); IR (neat, cm¹1): 1735, 1230, 1097, 989, 754, 727, 689,
676; 1H NMR (270 MHz, CDCl3): ¤ 7.99 (d, J = 8.1 Hz, 1H), 7.81
(d, J = 7.9 Hz, 1H), 7.50-7.21 (m, 7H), 4.27 (q, J = 7.1 Hz, 2H),
2.08 (s, 3H), 1.23 (t, J = 7.1 Hz, 3H); 13C NMR (68 MHz, CDCl3):
¤ 168.7, 160.5, 152.9, 137.0, 131.6, 128.6, 128.0, 126.1, 125.2,
122.9, 121.9, 121.0, 87.2, 86.3, 62.9, 51.1, 26.5, 13.9; HRMS
(ESI) Calcd for C20H17NO2S2Na: [M + Na]+ 390.0598. Found:
390.0593.
Methyl 2-Methyl-2-(phenylsulfanyl)propionate (3a): Pale
yellow oil; IR (neat, cm¹1): 1727, 1264, 1151, 1121, 751, 693;
1H NMR (270 MHz, CDCl3): ¤ 7.52-7.26 (m, 5H), 3.66 (s, 3H),
1.49 (s, 6H); 13C NMR (68 MHz, CDCl3): ¤ 174.1, 136.5, 131.1,
129.2, 128.4, 52.1, 51.0, 25.8; HRMS (ESI) Calcd for C11H14O2S-
Na: [M + Na]+ 233.0612. Found: 233.0603.
(R)-Ethyl 2-[(1,3-Benzothiazol-2-yl)sulfanyl]propionate (2p):
Colorless oil; 98% ee; the ee value was determined by chiral
HPLC analysis (DAICEL CHIRALCEL OD-H column, hexane/
i-PrOH = 150/1, flow rate = 1.0 mL min¹1): tR = 11.4 (S), 28.8
33
min (R); ½¡ꢀD = +130.0 (c 1.50, CHCl3); IR (neat, cm¹1): 1730,
1457, 1426, 1309, 1238, 1158, 1072, 1017, 990, 754, 725;
1H NMR (270 MHz, CDCl3): ¤ 7.86 (d, J = 8.1 Hz, 1H), 7.74 (d,
J = 7.7 Hz, 1H), 7.49-7.24 (m, 2H), 4.68 (q, J = 7.3 Hz, 1H),
4.32-4.10 (m, 2H), 1.71 (d, J = 7.3 Hz, 3H), 1.25 (t, J = 7.1 Hz,
3H); 13C NMR (68 MHz, CDCl3): ¤ 171.4, 164.0, 152.8, 135.3,
125.9, 124.3, 121.6, 120.9, 61.8, 45.1, 18.0, 14.1; HRMS
(ESI) Calcd for C12H13NO2S2Na: [M + Na]+ 290.0285. Found:
290.0277.
Methyl
2-Methyl-2-[(4-nitrophenyl)sulfanyl]propionate
(1S,2S,5R)-2-[(2-Isopropyl-5-methylcyclohexyl)sulfanyl]-1,3-
(3b): Spectral data are consistent with those of the literature.16a
Pale yellow oil; IR (neat, cm¹1): 1727, 1516, 1341, 1266, 1152,
1121, 852; 1H NMR (270 MHz, CDCl3): ¤ 8.16 (d, J = 8.7 Hz,
2H), 7.57 (d, J = 8.7 Hz, 2H), 3.72 (s, 3H), 1.56 (s, 6H); 13C NMR
(68 MHz, CDCl3): ¤ 173.7, 147.6, 140.9, 135.2, 123.4, 52.6, 51.6,
26.1.
38
benzothiazole (2q):
Colorless oil; ½¡ꢀD = +93.9 (c 0.93,
CHCl3); IR (neat, cm¹1): 1455, 1426, 987, 753, 725, 700; 1H NMR
(270 MHz, CDCl3): ¤ 7.85 (d, J = 8.1 Hz, 1H), 7.71 (d, J = 7.4
Hz, 1H), 7.41-7.05 (m, 1H), 7.28-7.22 (m, 1H), 4.56 (br, 1H),
2.28-2.17 (m, 1H), 1.97-1.55 (m, 4H), 1.48-1.35 (m, 1H), 1.33-
1.19 (m, 1H), 0.84 (m, 11H); 13C NMR (68 MHz, CDCl3): ¤ 167.3,
153.3, 135.1, 125.8, 123.9, 121.3, 120.7, 50.7, 48.6, 41.5, 35.2,
Methyl 2-Methyl-2-[(4-methoxyphenyl)sulfanyl]propionate
(3c): Pale yellow oil; IR (neat, cm¹1): 1726, 1492, 1285, 1265,

K. Kuroda et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 3 (2009)
391
1245, 1173, 1151, 1120, 1028, 828; 1H NMR (270 MHz, CDCl3): ¤
7.37 (d, J = 8.6 Hz, 2H), 6.84 (d, J = 8.6 Hz, 2H), 3.80 (s, 3H),
3.66 (s, 3H), 1.46 (s, 6H); 13C NMR (68 MHz, CDCl3): ¤ 174.2,
160.6, 138.3, 122.1, 114.1, 55.3, 52.1, 51.0, 25.7; HRMS (ESI)
Calcd for C12H16O3SNa: [M + Na]+ 263.0718. Found: 263.0712.
Methyl 2-Methyl-2-[(pyridin-2-yl)sulfanyl]propionate (3d):
Pale yellow oil; IR (neat, cm¹1): 1728, 1415, 1262, 1152, 1136,
Lett. 1997, 38, 3017. d) P. J. Brown, D. A. Winegar, K. D. Plunket,
L. B. Moore, M. C. Lewis, J. G. Wilson, S. S. Sundseth, C. S.
Koble, Z. Wu, J. M. Chapman, J. M. Lehmann, S. A. Kliewer,
T. M. Willson, J. Med. Chem. 1999, 42, 3785.
3
a) F. Y. Kwong, S. L. Buchwald, Org. Lett. 2002, 4, 3517.
b) C. G. Bates, R. K. Gujadhur, D. Venkataraman, Org. Lett. 2002,
4, 2803. c) C. Savarin, J. Srogl, L. S. Liebeskind, Org. Lett. 2002,
4, 4309. d) P. S. Herradura, K. A. Pendola, R. K. Guy, Org. Lett.
2000, 2, 2019. e) J. Ham, I. Yang, H. Kang, J. Org. Chem. 2004,
69, 3236. f) J. S. Bradshaw, J. A. South, R. H. Hales, J. Org.
Chem. 1972, 37, 2381. g) M. T. Martin, A. M. Thomas, D. G.
York, Tetrahedron Lett. 2002, 43, 2145.
1
1118, 758, 724; H NMR (270 MHz, CDCl3): ¤ 8.38 (d, J = 4.3
Hz, 1H), 7.49 (td, J = 7.7, 1.6 Hz, 1H), 7.18 (d, J = 7.9 Hz, 1H),
7.04-6.96 (m, 1H), 3.69 (s, 3H), 1.66 (s, 6H); 13C NMR (68 MHz,
CDCl3): ¤ 175.0, 157.0, 149.2, 135.9, 123.6, 120.1, 52.6, 50.6,
26.4; HRMS (ESI) Calcd for C10H13NO2SNa: [M + Na]+
234.0565. Found: 234.0564.
4
5
T. Kondo, T. Mitsudo, Chem. Rev. 2000, 100, 3205.
a) T. Mukaiyama, I. Kuwajima, Z. Suzuki, J. Org. Chem.
Methyl 2-Methyl-2-[(5-nitropyridin-2-yl)sulfanyl]propio-
nate (3e):
Spectral data are consistent with those of the
1963, 28, 2024. b) T. Mukaiyama, R. Matsueda, M. Suzuki,
Tetrahedron Lett. 1970, 11, 1901. c) T. Mukaiyama, Angew. Chem.,
Int. Ed. Engl. 1976, 15, 94.
literature.16a Pale yellow oil; IR (neat, cm¹1): 1731, 1585, 1566,
1511, 1338, 1264, 1145, 1123, 1098, 854, 750; 1H NMR (270
MHz, CDCl3): ¤ 9.17 (d, J = 2.3 Hz, 1H), 8.24 (dd, J = 8.8,
2.6 Hz, 1H), 7.27 (d, J = 8.9 Hz, 1H), 3.71 (s, 3H), 1.73 (s, 6H);
13C NMR (68 MHz, CDCl3): ¤ 174.1, 166.2, 144.5, 141.0, 130.4,
121.3, 52.9, 51.7, 26.2.
6
For reviews of the Mitsunobu reaction, see: a) O.
Mitsunobu, Synthesis 1981, 1. b) D. L. Hughes, Org. React.
1992, 42, 335. c) R. Dembinski, Eur. J. Org. Chem. 2004, 2763.
d) T. Y. S. But, P. H. Toy, Chem. Asian J. 2007, 2, 1340.
Methyl 2-Methyl-2-[(1-methyl-1H-tetrazol-5-yl)sulfanyl]-
propionate (3f): Pale yellow oil; IR (neat, cm¹1): 1730, 1268,
7
4099.
8
E. J. Corey, K. A. Cimprich, Tetrahedron Lett. 1992, 33,
1
1156, 1121; H NMR (270 MHz, CDCl3): ¤ 4.02 (s, 3H), 3.71 (s,
a) D. H. Valentine, J. H. Hillhouse, Synthesis 2003, 317.
3H), 1.74 (s, 6H); 13C NMR (68 MHz, CDCl3): ¤ 172.7, 150.5,
54.4, 53.2, 34.0, 26.6; HRMS (ESI) Calcd for C7H12N4O2SNa:
[M + Na]+ 239.0579. Found: 239.0570.
b) J. Skarżewski, A. Gupta, E. Wojaczyńska, R. Siedlecka, Synlett
2003, 1615. c) H. Kotsuki, K. Matsumoto, H. Nishizawa,
Tetrahedron Lett. 1991, 32, 4155. d) I. Nakagawa, K. Aki, T.
Hata, J. Chem. Soc., Perkin Trans. 1 1983, 1315. e) I. Nakagawa,
T. Hata, Tetrahedron Lett. 1975, 16, 1409. f) K. A. M. Walker,
Tetrahedron Lett. 1977, 18, 4475.
Methyl 2-Methyl-2-[(6-nitro-1,3-benzothiazol-2-yl)sulfanyl]-
propionate (3g): Yellow solid; mp 114-115 °C; IR (neat, cm¹1):
1723, 1433, 1328, 1266, 1122, 1043, 1005, 836, 747; 1H NMR
(270 MHz, CDCl3): ¤ 8.69 (d, J = 2.1 Hz, 1H), 8.29 (dd, J = 8.8,
2.2 Hz, 1H), 7.92 (d, J = 9.1 Hz, 1H), 3.77 (s, 3H), 1.82 (s, 6H);
13C NMR (68 MHz, CDCl3): ¤ 173.2, 170.2, 156.7, 144.2, 135.8,
121.7, 121.6, 117.3, 54.7, 53.1, 26.4; HRMS (ESI) Calcd for
C12H12N2O4S2Na: [M + Na]+ 335.0136. Found: 335.0130.
Methyl 2-[(1,3-Benzoxazol-2-yl)sulfanyl]-2-methylpropio-
9
For other methods for preparation of alkyl aryl sulfides
from alcohols, see: a) S.-C. Tsay, L. C. Lin, P. A. Furth, C. C.
Shum, D. B. King, S. F. Yu, B.-L. Chen, J. R. Hwu, Synthesis
1993, 329. b) Y. Guindon, R. Frenette, R. Fortin, J. Rokach, J. Org.
Chem. 1983, 48, 1357. c) Y. Kawano, N. Kaneko, T. Mukaiyama,
Chem. Lett. 2005, 34, 1612.
nate (3h):
Spectral data are consistent with those of the
10 For the synthesis of chiral building blocks possessing
sulfur-containing quaternary carbons, see: a) B. Strijtveen, R. M.
Kellogg, Tetrahedron 1987, 43, 5039. b) O. Stratmann, B. Kaiser,
R. Fröhlich, O. Meyer, D. Hoppe, Chem.®Eur. J. 2001, 7, 423.
c) F. Marr, D. Hoppe, Org. Lett. 2002, 4, 4217. d) F. Marr, R.
Fröhlich, D. Hoppe, Org. Lett. 1999, 1, 2081. e) J. M. McFadden,
G. L. Frehywot, C. A. Townsend, Org. Lett. 2002, 4, 3859. f) X.
Zhang, Z. Qu, Z. Ma, W. Shi, X. Jin, J. Wang, J. Org. Chem. 2002,
67, 5621.
11 For example of SN2 displacement at a quaternary center
with various nucleophiles, see: a) Y.-J. Shi, D. L. Hughes, J. M.
McNamara, Tetrahedron Lett. 2003, 44, 3609. b) A. Avenoza, J. H.
Busto, F. Corzana, G. Jiménez-Osés, J. M. Peregrina, Chem.
Commun. 2004, 980. c) T. Kitazume, T. Sato, T. Kobayashi, J. T.
Lin, J. Org. Chem. 1986, 51, 1003. d) N. D. Smith, M. Goodman,
Org. Lett. 2003, 5, 1035. e) F. Effenberger, S. Gaupp, Tetrahedron:
Asymmetry 1999, 10, 1765. f) J. Wachtmeister, A. Mühlman, B.
Classon, B. Samuelsson, Tetrahedron 1999, 55, 10761. g) D. F.
Taber, Y. He, M. Xu, J. Am. Chem. Soc. 2004, 126, 13900. h) Y.
Masaki, H. Arasaki, M. Iwata, Chem. Lett. 2003, 32, 4.
12 For reviews of 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.
literature.16a Pale yellow oil; IR (neat, cm¹1): 1735, 1503, 1452,
1267, 1237, 1156, 1118, 1091, 743; 1H NMR (270 MHz, CDCl3): ¤
7.69-7.60 (m, 1H), 7.50-7.41 (m, 1H), 7.35-7.23 (m, 2H), 3.75 (s,
3H), 1.80 (s, 6H); 13C NMR (68 MHz, CDCl3): ¤ 173.3, 161.3,
151.4, 141.7, 124.4, 124.2, 119.1, 110.0, 53.1, 53.0, 26.6.
Methyl 2-(Benzoylsulfanyl)-2-methylpropionate (3i): Color-
less oil; IR (neat, cm¹1): 1735, 1660, 1261, 1208, 1156, 1126, 908,
688; 1H NMR (270 MHz, CDCl3): ¤ 7.90 (d, J = 7.4 Hz, 2H), 7.56
(t, J = 7.2 Hz, 1H), 7.43 (t, J = 7.6 Hz, 2H), 3.76 (s, 3H), 1.69 (s,
6H); 13C NMR (68 MHz, CDCl3): ¤ 190.9, 174.3, 136.5, 133.4,
128.5, 127.1, 53.0, 51.1, 26.2; HRMS (ESI) Calcd for C12H14O3S-
Na: [M + Na]+ 261.0561. Found: 261.0559.
K. K. was granted a Research Fellowship of the Japan
Society for the Promotion of Science for Young Scientists.
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21 These bulkyl substituents at 2- and 6-positions of 1,4-
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alkylation of the phenoxide anion of intermediate A. This
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in previous papers.12b,16a
27 The yield of the desired sulfide obtained by using an azide
was lower than that using a benzoquinone derivative only when a
sulfur nucleophile having a high pKa value such as benzenethiol or
4-methoxybenzenethiol was used. This indicates that the basicity
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intermediate A (Scheme 2). On the other hand, reaction of BtzSH
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undesired olefins. Since the yield of the desired product obtained
by using an azide is higher than that using a benzoquinone
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