Facile deprotection of dithioacetals by using a novel 1,4-benzoquinone/cat. NaI system

Article abstract of DOI:10.1016/j.tet.2013.08.061

The combination of 1,4-benzoquinone and a catalytic amount of NaI was found to be effective for the deprotection of dithioacetals. The reactions proceeded efficiently under mild, near-neutral reaction conditions, producing a wide range of aryl and alkyl aldehydes and ketones generally in high yields with good functional group compatibility. The method developed therefore represents a general, facile, and highly applicable approach for deprotecting dithioacetals.

Full text of DOI:10.1016/j.tet.2013.08.061

Tetrahedron 69 (2013) 9192e9199
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Tetrahedron
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Facile deprotection of dithioacetals by using a novel
1,4-benzoquinone/cat. NaI system
*
*
Kiyofumi Inamoto , Tetsuya Yamada, Sei-ichi Kato, Shoko Kikkawa, Yoshinori Kondo
Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 July 2013
Received in revised form 20 August 2013
Accepted 22 August 2013
Available online 29 August 2013
The combination of 1,4-benzoquinone and a catalytic amount of NaI was found to be effective for the
deprotection of dithioacetals. The reactions proceeded efficiently under mild, near-neutral reaction
conditions, producing a wide range of aryl and alkyl aldehydes and ketones generally in high yields with
good functional group compatibility. The method developed therefore represents a general, facile, and
highly applicable approach for deprotecting dithioacetals.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Desulfurization
Deprotection
1,3-Dithianes
Aldehydes
Ketones
1. Introduction
proposed.9 Kirihara et al. recently developed a similar deprotection
method based on the iodonium ion, derived from a catalytic com-
Dithioacetals have extensively been employed as important
protecting groups for carbonyl moieties in organic synthesis due to
their stability toward both acidic and basic conditions.1 Further-
more, cyclic dithioacetals, such as 1,3-dithianes can be considered
as useful building blocks, serving as acyl anion equivalents, which
participate in CeC bond forming reactions.2 A variety of procedures
have so far been developed for the deprotection of dithioacetals,
including heavy metal (e.g., Hg) mediated processes3 as well as
some oxidative methods (e.g., using DDQ,4 hypervalent iodines,5
mCPBA6), most of these methods suffer from several drawbacks,
such as harsh reaction conditions, use of a stoichiometric amount
or an excess of toxic and/or expensive (metal) reagents, and a nar-
row substrate scope. Use of electrophilic halonium ions also pro-
vides another approach for the deprotection. An excess amount of
N-halosuccinimides (NBS and NCS) has classically been chosen for
this purpose.7 In 2001, the combination of H2O2 and NH4Br in the
presence of a catalytic amount of V2O5, possibly forming a bromo-
nium cation in situ, has been reported by Khan et al. to effect
dethioacetalization.8 Oxone was also successfully employed as an
oxidant in the presence of KBr, mediating the deprotection of
dithioacetals, in which the formation of bromonium cation was
bination of TaCl5/NaI or NbCl5/NaI along with H2O2.10 Herein, we
describe a new entry for the deprotection of dithioacetals. The
method features the use of a novel combination, such as 1,4-
benzoquinone (BQ)/catalytic NaI under an air atmosphere, which
successfully effects the deprotection process under mild, near-
neutral conditions to afford a wide range of aryl and alkyl alde-
hydes and ketones generally in high yields. Indeed, BQ has never
been employed as an oxidant for this kind of deprotection. The
method developed provides a general, facile, thus highly applicable
approach for dethioacetalization.11
2. Results and discussion
Using BQ as a stoichiometric oxidant, the deprotection of 1,3-
dithiane 1a in the presence of a variety of metal halides was first
examined (Table 1). Pleasingly, most of the metal iodides employed
exhibited a remarkable catalytic activity, providing aldehyde 2a in
high yields (entries 1, 3e6). For example, the combination of
1 mol % NaI and 1.2 equiv of BQ in the solvent system, such as H2O/
MeCN (1:10) provided the desired product 2a in 90% isolated yield
(entry 6). Interestingly, the corresponding bromide (NaBr) and
chloride (NaCl) turned out much less efficient for the process (en-
tries 7 and 8). Examination of the optimal solvent led to the finding
that H2O/MeCN provided the best result (entries 6 vs 9e13). Es-
sentially, the reaction did not proceed at all in the absence of BQ
(entry 14). In addition, only a moderate yield was obtained when
* Corresponding authors. Tel.: þ81 22 795 3906; fax: þ81 22 795 5917; e-mail
addresses: inamoto@m.tohoku.ac.jp (K. Inamoto), ykondo@m.tohoku.ac.jp
(Y. Kondo).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.08.061

K. Inamoto et al. / Tetrahedron 69 (2013) 9192e9199
9193
Table 2
Deprotection of dithianes derived from aldehydesa
Table 1
Effect of reaction parametersa
Entry
1
Substrate
1
Time (h)
40
Yieldb (%)
Entry
Catalyst (x mol %)
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
CuI (10)
AgI (10)
AuI (2)
LiI (1)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
Acetone
THF
AcOEt
DMSO
DMF
MeCN
MeCN
MeCN
14
36
9
98
1a (R0¼4-OMe)
90
8
(95)c
1b (R0¼3-OMe)
1c (R0¼2-OMe)
1d (R0¼4-CN)
1e (R0¼4-NO2)
1f (R0¼4-CO2Me)
1g (R0¼4-Cl)
24
24
24
36
31
24
24
48
22
91
98
38
38
40
48
48
24
24
24
24
24
24
24
40
quant.
2
3
4
5
6
7
8
9
KI (1)
quant.
NaI (1)
NaCl (1)
NaBr (1)
NaI (1)
NaI (1)
NaI (1)
NaI (1)
NaI (1)
NaI (1)
None
quant. (90)c
86c
76c
86c
86
3
3
9
94
92
81
68
56
0
1h (R0¼4-Br)
1i (R0¼2-I)
82
10
11
12
13
14d
15
16e
72c
78
10
1j (R0¼4-OH)
47
quant.
NaI (1)
11
12
1k
1l
24
48
91
a
Reaction was run on a 0.5 mmol scale in H2O/solvent (2.2 mL).
b
Yield based on 1H NMR spectroscopy using 1,1,2-trichloroethane as an internal
standard.
c
Isolated yield.
In the absence of BQ.
Under an Ar atmosphere.
96c
d
e
13
14
1m
1n
48
72
quant.d
the deprotection was carried out in the absence of NaI (entry 15).
These results clearly indicate that both BQ and NaI are crucial for
the efficient deprotection. Moreover, it is interesting to note that
the use of an Ar atmosphere instead of an air atmosphere resulted
in the formation of 2a in high yield, suggesting that the oxygen is
not involved in the process (entry 16).
96d
The newly developed deprotection method was further in-
vestigated in the reactions of a range of dithioacetals 1bet (Table 2).
Substrates 1aef possessing an electron-donating (eOMe) or an
electron-withdrawing group (eCN, eNO2, eCO2Me) at the para-,
meta-, or ortho-position of the benzene ring were all suitable for the
process, providing the corresponding aldehydes 2aef in high yields
(entries 1e6). Halogen atoms, such as eCl, eBr, and eI, as well as
phenolic eOH on the benzene ring were well tolerated during the
process (entries 7e10). Moreover, reactions of both condensed ar-
omatic compound 1l and heteroaromatic compound 1m proceeded
smoothly under the optimized conditions to give rise to aldehydes
2l and 2m in excellent yields (entries 12 and 13). In addition, the
conversions of aliphatic aldehyde-derived dithianes 1nep were
successfully carried out using our method (entries 14e16). It is
worth noting that the alkene moiety of compound 1p remained
intact during the process (entry 16). The reactions of dithiane 1q,
possessing an alcoholic eOH, and its TBDPS-protected dithiane 1r
also successfully delivered the deprotected aldehydes (entries 17
and 18). Furthermore, dithiolane 1s and acyclic dithioacetal 1t were
successfully deprotected under our catalytic conditions (entries 19
and 20).
15
16
17
18
1o
1p
1q
1r
29
72
48
25
38
74d
73
70
19
20
1s
1t
24
48
79
85
Several kinds of ketone-derived dithioacetals 1uez were also
treated with the above-mentioned BQ/cat. NaI system, all of which
resulted in the successful deprotection to produce 2uez in good-to-
high yields (Table 3).
Although the precise reaction mechanism remains to be eluci-
dated, the process probably involves the catalytic cycle similar to
that in the previous report by Kirihara et al., in which iodonium
cation is formed in situ in the presence of NaI and the oxidant.10 To
a
Reaction was run on a 0.5 mmol scale in H2O/MeCN (2.2 mL).
Isolated yield.
b
c
Yield based on 1H NMR spectroscopy using 1,1,2-trichloroethane as an internal
standard.
d
Yield determined by GC analysis versus a calibrated internal standard.
determine the involvement of such an iodonium species,
g,d-

9194
K. Inamoto et al. / Tetrahedron 69 (2013) 9192e9199
Table 3
dithiane moiety was transformed into the corresponding disulfide
during the reaction (Scheme 2).
Deprotection of dithianes derived from ketonesa
Entry
1
Substrate
1
Time (h)
35
Yieldb (%)
quant.
1u
Scheme 2. Disulfide formation.
2
3
1v
19
19
70
3. Conclusions
In summary, we have developed a novel, efficient method for
the deprotection of dithioacetals using the combination consisting
of BQ and a catalytic amount of NaI. Using our method, a wide range
of aryl and alkyl aldehydes and ketones can be obtained generally
in high yields under mild conditions. Good functional group com-
patibility is also observed in the process. Investigation to unveil the
reaction mechanism as well as to broaden the substrate scope is
currently underway. We are also applying this novel catalytic sys-
tem to other oxidation processes.
1w
79c
4
5
6
1x
1y
12
48
71
81d
4. Experimental section
4.1. General
Dithioacetals (1aez except 1w) were prepared according to
the previously reported methods from the corresponding alde-
hydes or ketones.13,14 Compound 1w was also prepared according
to the previously reported method.15 All other chemicals
employed in this work are commercially available and were used
as received. Melting points were measured with a Yazawa micro
melting point apparatus and uncorrected. IR spectra were recor-
ded on a SHIMADZU IRAffinity. 1H NMR spectra were recorded on
1z
19
71
a
Reaction was run on a 0.5 mmol scale in H2O/MeCN (2.2 mL).
Isolated yield.
b
c
Yield based on 1H NMR spectroscopy using 1,1,2-trichloroethane as an internal
standard.
a JEOL JNM-AL400 (400 MHz) spectrometer. Chemical shifts (d)
d
Yield determined by GC analysis versus a calibrated internal standard.
are given from TMS (0 ppm) and coupling constants are
expressed in hertz (Hz). The following abbreviations are used:
s¼singlet, d¼doublet, t¼triplet, dd¼double doublet, td¼triple
doublet, m¼multiplet, and br s¼broad singlet. 13C NMR spectra
were recorded on a JEOL JNM-AL400 (100 MHz) spectrometer and
alkenoic acid 3 was subjected to the reaction using 10 equiv NaI and
10 equiv BQ in H2O/MeCN solvent (Scheme 1).
chemical shifts (d
) are given from 13CDCl3 (77.0 ppm). Mass
spectra and high resolution mass spectra were measured on
a JEOL JMS-DX 303 and JMS-700/JMS-T 100 GC instruments, re-
spectively. Elemental analyses were performed by Yanaco CHN
CORDER MT-6.
4.2. Representative procedure for preparation of 1,3-
dithianes
Scheme 1. Iodolactonization.
4.2.1. Method A.13 CuSO4 (3.5 g, 22.0 mmol) was added to a mix-
ture of 4-methoxybenzaldehyde (2.7 g, 19.7 mmol) and 1,3-
propandithiol (2.3 g, 21.0 mmol) in CH2Cl2 (100 mL) at room
temperature and stirred at the same temperature until the start-
ing aldehyde had been completely consumed (checked by TLC
analysis). The reaction mixture was filtered through a pad of Celite
and the filtrate was concentrated in vacuo. The residue was pu-
rified by flash column chromatography (eluent: hexane/
AcOEt¼5:1) followed by recrystallization (AcOEt/hexane) to give
Although the yield was not high, the iodolactonization product 4
was indeed obtained, suggesting the possible formation of the
iodonium cation during our deprotection process.12 In addition,
radical scavengers, such as BHT (di-tert-butylhydroxytoluene) and
galvinoxyl were found to have no effect on the process, indicating
that the reaction might be proceeding via an ionic pathway, rather
than a radical pathway. Furthermore, from the reaction of 1aa
under the optimal conditions (Scheme 2), it was found that the

K. Inamoto et al. / Tetrahedron 69 (2013) 9192e9199
9195
2-(4-methoxyphenyl)-1,3-dithiane 1a (3.2 g, 71%) as colorless
prisms.
3.04e3.11 (m, 2H), 5.23 (s, 1H), 7.65 (d, J¼8.8 Hz, 2H), 8.20 (d,
J¼8.8 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 24.7, 31.7,
50.3, 123.9, 128.9, 146.1, 147.6. LRMS (EI) m/z: 241 (Mþ). HRMS:
calcd for C10H11NO2S2: 241.0231, found: 241.0222.
4.2.2. Method B.14 Under an Ar atmosphere, 1,3-propanedithiol
(1.1 g, 10.5 mmol) was added to
a mixture of methyl 4-
formylbenzoate (1.6 g, 10.0 mmol) and Na2SO4 (1.0 g) in CHCl3
(15 mL) at room temperature. After distilled BF3$OEt2 (1.36 mL,
11.0 mmol) was added dropwise to the mixture at 0 ꢀC, the whole
reaction mixture was gradually warmed up to room temperature
and then stirred overnight. After the addition of saturated aqueous
NaHCO3 (50 mL), the mixture was extracted with CHCl3 (50 mLꢁ2)
and the organic layer was washed with NaHCO3 (50 mLꢁ1), H2O
(50 mLꢁ1), and brine (50 mLꢁ1). The organic layer was dried over
MgSO4 and concentrated in vacuo. The residue was purified by flash
column chromatography (eluent: hexane/AcOEt¼5:1) followed by
recrystallization (AcOEt) to give methyl 4-(1,3-dithian-2-yl)ben-
zoate 1f (2.3 g, 91%) as colorless needles.
4.2.8. Methyl 4-(1,3-dithian-2-yl)benzoate (1f).17 Prepared accord-
ing to the Method B. Recrystallized from AcOEt, colorless needles,
mp 138e140 ꢀC (lit.17 mp 132e134 ꢀC). IR (neat): 2948, 2901, 1715,
1559, 1271, 1176, 1111, 1018, 872, 736, 699 cmꢂ1. 1H NMR (400 MHz,
CDCl3/TMS)
d (ppm): 1.88e2.00 (m, 1H), 2.15e2.22 (m, 1H),
2.90e2.95 (m, 2H), 3.03e3.10 (m, 2H), 3.91 (s, 3H), 5.20 (s, 1H), 7.55
(d, J¼8.6 Hz, 2H), 8.01 (d, J¼8.6 Hz, 2H). 13C{1H} NMR (100 MHz,
CDCl3) d (ppm): 25.0, 31.9, 51.0, 52.1, 127.9, 130.0, 130.1, 143.9, 166.5.
LRMS (EI) m/z: 254 (Mþ). HRMS: calcd for C12H14O2S2: 254.0435,
found: 254.0438.
4.2.9. 2-(4-Chlorophenyl)-1,3-dithiane (1g).15 Prepared according
to the Method A. Recrystallized from AcOEt/hexane, colorless
prisms, mp 88e90 ꢀC (lit.15 mp 82e83 ꢀC). IR (neat): 2891, 1487,
4.2.3. 2-(4-Methoxyphenyl)-1,3-dithiane (1a).15 Prepared according
to the Method A. Recrystallized from AcOEt/hexane, colorless
prisms, mp 116e117 ꢀC (lit.15 mp 115e118 ꢀC). IR (neat): 2901, 1607,
1405, 1275, 1169, 1083, 851, 755, 671 cmꢂ1 1H NMR (400 MHz,
.
CDCl3/TMS)
d (ppm): 1.86e1.96 (m, 1H), 2.12e2.19 (m, 1H),
1559, 1507, 1247, 1179, 1109, 1030, 815, 775, 675 cmꢂ1
.
1H NMR
2.87e2.92 (m, 2H), 3.00e3.07 (m, 2H), 5.12 (s, 1H), 7.30 (d, J¼8.6 Hz,
(400 MHz, CDCl3/TMS)
d
(ppm): 1.90e1.93 (m, 1H), 2.13e2.18 (m,
2H), 7.40 (d, J¼8.6 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm):
1H), 2.88e2.92 (m, 2H), 3.01e3.08 (m, 2H), 3.79 (s, 3H), 5.13 (s, 1H),
25.0, 32.0, 50.5, 128.8, 129.1, 134.0, 137.5. LRMS (EI) m/z: 230 (Mþ).
6.86 (d, J¼8.8 Hz, 2H), 7.39 (d, J¼8.8 Hz, 2H). 13C{1H} NMR
HRMS: calcd for C10H1135ClS2: 229.9991, found: 229.9987.
(100 MHz, CDCl3)
d (ppm): 25.0, 32.1, 50.7, 55.2, 114.0, 128.9, 131.2,
159.5. LRMS (EI) m/z: 226 (Mþ). HRMS: calcd for C11H14OS2:
4.2.10. 2-(4-Bromophenyl)-1,3-dithiane (1h).18 Prepared according
to the Method B. Recrystallized from AcOEt/hexane, colorless
needles, mp 93e94 ꢀC (lit.18 mp 82e83 ꢀC). IR (neat): 2944, 2899,
1481, 1411, 1275, 1066, 1008, 854, 811, 753 cmꢂ1. 1H NMR (400 MHz,
226.0486, found: 226.0477.
4.2.4. 2-(3-Methoxyphenyl)-1,3-dithiane (1b).15 Prepared according
to the Method B. Recrystallized from AcOEt/hexane, colorless
prisms, mp 61e63 ꢀC (lit.15 mp 62.5e62.9 ꢀC). IR (neat): 2934, 2899,
CDCl3/TMS)
d (ppm): 1.87e1.97 (m, 1H), 2.13e2.19 (m, 1H),
2.87e2.93 (m, 2H), 3.00e3.08 (m, 2H), 5.11 (s, 1H), 7.35 (d, J¼8.8 Hz,
1595, 1490, 1266, 1157, 1085, 1033, 861, 746 cmꢂ1
.
1H NMR
2H), 7.46 (d, J¼8.8 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm):
(400 MHz, CDCl3/TMS)
d
(ppm): 1.88e2.00 (m, 1H), 2.14e2.21 (m,
24.9, 31.9, 50.6, 122.3, 129.5, 131.8, 138.1. LRMS (EI) m/z: 274 (Mþ).
1H), 2.89e2.94 (m, 2H), 3.03e3.10 (m, 2H), 3.81 (s, 3H), 5.14 (s, 1H),
HRMS: calcd for C10H1179BrS2: 273.9486, found: 273.9469.
6.83e6.86 (m, 1H), 7.03e7.06 (m, 2H), 7.22e7.27 (m, 1H). 13C{1H}
NMR (100 MHz, CDCl3)
d
(ppm): 25.1, 32.1, 51.5, 55.2, 113.0, 114.4,
4.2.11. 2-(2-Iodophenyl)-1,3-dithiane (1i).19 Prepared according to
the Method B. Recrystallized from AcOEt/hexane, colorless prisms,
mp 109e111 ꢀC. IR (neat): 2897, 1560, 1462, 1420, 1272, 1175, 1160,
120.0, 129.7, 140.5, 159.8. LRMS (EI) m/z: 226 (Mþ). HRMS: calcd for
C11H14OS2: 226.0486, found: 226.0485.
1011, 910, 742 cmꢂ1 1H NMR (400 MHz, CDCl3/TMS)
. d (ppm):
4.2.5. 2-(2-Methoxyphenyl)-1,3-dithiane (1c).15 Prepared according
to the Method B. Recrystallized from AcOEt/hexane, colorless
plates, mp 127e129 ꢀC (lit.15 mp 128e129 ꢀC). IR (neat): 2959, 2897,
2831,1490,1289,1242,1096,1051,1021, 756, 719, 674 cmꢂ1. 1H NMR
1.88e2.00 (m, 1H), 2.15e2.22 (m, 1H), 2.90e2.96 (m, 2H), 3.09e3.16
(m, 2H), 5.42 (s, 1H), 6.97 (td, J1¼7.8 Hz, J2¼1.4 Hz, 1H), 7.35 (td,
J1¼7.8 Hz, J2¼1.4 Hz,1H), 7.65 (dd, J1¼7.8 Hz, J2¼1.4 Hz,1H), 7.82 (dd,
J1¼7.8 Hz, J2¼1.4 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm):
(400 MHz, CDCl3/TMS)
d
(ppm): 1.88e1.98 (m, 1H), 2.12e2.19 (m,
25.1, 32.3, 56.7, 99.4, 128.9, 129.1, 129.9, 139.6, 141.5. LRMS (EI) m/z:
1H), 2.86e2.91 (m, 2H), 3.07e3.14 (m, 2H), 3.86 (s, 3H), 5.71 (s, 1H),
6.86 (d, J¼8.3 Hz, 1H), 6.96 (d, J¼8.3 Hz, 1H), 7.25 (d, J¼8.3 Hz, 1H),
322 (Mþ). HRMS: calcd for C10H11IS2: 321.9347, found: 321.9349.
7.58 (d, J¼8.3 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3)
d
(ppm): 25.3,
4.2.12. 2-(4-Hydroxyphenyl)-1,3-dithiane (1j).20 Prepared accord-
ing to the Method B. Recrystallized from AcOEt/hexane, colorless
prisms, mp 156e158 ꢀC (lit.20 mp 155e158 ꢀC). IR (neat): 3368,
32.4, 43.6, 55.7, 110.7, 121.0, 127.3, 129.1, 129.3, 155.4. LRMS (EI) m/z:
226 (Mþ). HRMS: calcd for C11H14OS2: 226.0486, found: 226.0491.
2887, 1511, 1442, 1241, 1103, 851, 815, 762, 674 cmꢂ1 1H NMR
.
4.2.6. 2-(4-Cyanophenyl)-1,3-dithiane (1d).11b Prepared according
to the Method B. Recrystallized from AcOEt/hexane, colorless
needles, mp 115e116 ꢀC. IR (neat): 2908, 2222, 1607, 1506, 1414,
(400 MHz, CDCl3/TMS) d (ppm): 1.85e1.97 (m, 1H), 2.13e2.20 (m,
1H), 2.87e2.92 (m, 2H), 3.01e3.09 (m, 2H), 4.81 (br s, 1H), 5.12 (s,
1H), 6.78 (d, J¼8.8 Hz, 2H), 7.34 (d, J¼8.8 Hz, 2H). 13C{1H} NMR
1278, 1178, 883, 864, 767 cmꢂ1
.
1H NMR (400 MHz, CDCl3/TMS)
(100 MHz, CDCl3) d (ppm): 25.1, 32.2, 50.7, 115.5, 129.2, 131.5, 155.5.
d
(ppm): 1.89e2.04 (m, 1H), 2.16e2.23 (m, 1H), 2.90e2.96 (m, 2H),
LRMS (EI) m/z: 212 (Mþ). HRMS: calcd for C10H12OS2: 212.0330,
3.03e3.10 (m, 2H), 5.18 (s, 1H), 7.59 (d, J¼8.8 Hz, 2H), 7.63 (d,
found: 212.0328.
J¼8.8 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 24.8, 31.7,
50.7, 112.2, 118.4, 128.7, 132.5, 144.2. LRMS (EI) m/z: 221 (Mþ).
HRMS: calcd for C11H11NS2: 221.0333, found: 221.0321.
4.2.13. 2-(3,4-Methylenedioxyphenyl)-1,3-dithiane (1k).21 Prepared
according to the Method B. Recrystallized from AcOEt/hexane,
colorless prisms, mp 87e89 ꢀC (lit.21 mp 84.5e85.5 ꢀC). IR (neat):
4.2.7. 2-(4-Nitrophenyl)-1,3-dithiane (1e).16 Prepared according to
the Method A. Recrystallized from AcOEt, yellowish prisms, mp
141e143 ꢀC (lit.16 mp 144e145 ꢀC). IR (neat): 2908, 1603, 1513, 1409,
1342,1272,1111, 871, 729, 691 cmꢂ1. 1H NMR (400 MHz, CDCl3/TMS)
2886, 1499, 1440, 1362, 1253, 1240, 1171, 1038, 933, 758 cmꢂ1
.
1H
NMR (400 MHz, CDCl3/TMS)
d (ppm): 1.84e1.95 (m, 1H), 2.11e2.18
(m, 1H), 2.85e2.91 (m, 2H), 2.99e3.07 (m, 2H), 5.08 (s, 1H), 5.94 (s,
2H), 6.75 (d, J¼7.8 Hz, 1H), 6.93 (dd, J1¼7.8 Hz, J2¼1.5 Hz, 1H), 6.98
d
(ppm): 1.90e2.02 (m, 1H), 2.16e2.24 (m, 1H), 2.91e2.97 (m, 2H),
(d, J¼1.5 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 25.0, 32.1,

9196
K. Inamoto et al. / Tetrahedron 69 (2013) 9192e9199
51.1, 101.1, 108.3 (2C), 121.2, 132.9, 147.5, 147.7. LRMS (EI) m/z: 240
powder, mp 122e123 ꢀC. IR (neat): 2955, 2855, 2364, 1425, 1106,
1050, 872, 822, 758 cmꢂ1. 1H NMR (400 MHz, CDCl3/TMS)
(ppm):
(Mþ). HRMS: calcd for C11H12O2S2: 240.0279, found: 240.0262.
d
1.09 (s, 9H), 1.87e1.99 (m, 1H), 2.13e2.20 (m, 1H), 2.88e2.93 (m,
2H), 3.03e3.10 (m, 2H), 4.75 (s, 2H), 5.17 (s, 1H), 7.30e7.44 (m, 10H),
4.2.14. 2-(2-Naphthyl)-1,3-dithiane (1l).22 Prepared according to
the Method B. Recrystallized from AcOEt/hexane, colorless needles,
mp 113e115 ꢀC (lit.22 mp 112 ꢀC). IR (neat): 2891, 1599, 1505, 1420,
1279, 1185, 896, 868, 816, 758 cmꢂ1. 1H NMR (400 MHz, CDCl3/TMS)
7.66e7.69 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 19.3,
25.1, 26.8, 32.1, 51.3, 65.2, 126.3, 127.6, 127.7, 129.7, 133.4, 135.5,
137.7, 141.4. LRMS (EI) m/z: 464 (Mþ). HRMS: calcd for C27H32OS2Si:
464.1664, found: 464.1649.
d
(ppm): 1.90e2.03 (m, 1H), 2.13e2.20 (m, 1H), 2.90e2.95 (m, 2H),
3.04e3.11 (m, 2H), 5.32 (s, 1H), 7.43e7.48 (m, 2H), 7.57 (dd,
J1¼8.8 Hz, J2¼1.9 Hz, 1H), 7.79e7.83 (m, 3H), 7.95 (d, J¼1.9 Hz, 1H).
4.2.21. 2-(4-Methoxyphenyl)-1,3-dithiolane
(1s).25 Prepared
13C{1H} NMR (100 MHz, CDCl3)
d
(ppm): 25.1, 32.1, 51.5, 125.6,
according to the method A. Recrystallized from AcOEt/hexane,
126.22, 126.25, 126.8, 127.6, 128.0, 128.4, 133.2, 133.3, 136.4. LRMS
(EI) m/z: 246 (Mþ). HRMS: calcd for C14H14S2: 246.0537, found:
246.0529.
colorless needles, mp 60e61 ꢀC (lit.25 mp 60.2e61 ꢀC). IR (neat):
2919, 1606, 1585, 1509, 1251, 1228, 1175, 1030, 838, 754 cmꢂ1 1H
.
NMR (400 MHz, CDCl3/TMS) d (ppm): 3.30e3.38 (m, 2H), 3.46e3.54
(m, 2H), 3.79 (s, 3H), 5.64 (s, 1H), 6.84 (d, J¼8.8 Hz, 2H), 7.45 (d,
4.2.15. 2-(2-Thienyl)-1,3-dithiane (1m).23 Prepared according to the
J¼8.8 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 40.2, 55.3,
Method A. Recrystallized from hexane, colorless prisms, mp
56.1, 113.9, 129.1, 131.8, 159.4. LRMS (EI) m/z: 212 (Mþ). HRMS:
calcd for C10H12OS2: 212.0330, found: 212.0315.
23
ꢀ
77e78 ꢀC (lit. mp 79e80 C). IR (neat): 2902, 2362, 2342, 1419,
1257, 1181, 904, 850, 764 cmꢂ1
.
1H NMR (400 MHz, CDCl3/TMS)
d
(ppm): 1.92e2.03 (1H, m), 2.12e2.20 (1H, m), 2.91e3.03 (4H, m),
4.2.22. 1-[Bis(ethylthio)methyl]-4-methoxybenzene (1t).26 Prepared
according to the method A. Recrystallized from AcOEt/hexane,
colorless plates, mp 39e40 ꢀC (lit.26 mp 40e41 ꢀC). IR (neat): 2967,
5.41 (1H, s), 6.96 (1H, dd, J1¼5.4 Hz, J2¼3.4 Hz), 7.16 (1H, dd,
J1¼3.4 Hz, J2¼1.0 Hz), 7.27 (1H, dd, J1¼5.4, J2¼1.0 Hz). 13C{1H} NMR
(100 MHz, CDCl3)
d
(ppm): 25.0, 31.0, 44.7, 125.7, 126.2, 126.8, 142.6.
1610, 1509, 1302, 1257, 1174, 1107, 1025, 841, 770 cmꢂ1 1H NMR
.
LRMS (EI) m/z: 201 (Mþ). HRMS: C8H10S3: 201.9945, found:
(400 MHz, CDCl3/TMS)
d
(ppm): 1.22 (t, J¼7.3 Hz, 6H), 2.47e2.64 (m,
201.9927.
4H), 3.80 (s, 3H), 4.91 (s, 1H), 6.86 (d, J¼8.3 Hz, 2H), 7.37 (d,
J¼8.3 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 14.3, 26.2,
4.2.16. 2-Cyclohexyl-1,3-dithiane (1n).24 Prepared according to the
Method A. Recrystallized from hexane, colorless plates, mp
52e54 ꢀC (lit.24 mp 49e50 ꢀC). IR (neat): 3753, 2921, 2850, 2360,
1653, 1559, 1276, 1184, 908, 759 cmꢂ1. 1H NMR (400 MHz, CDCl3/
51.8, 55.2, 113.8, 128.8, 132.5, 159.1. LRMS (FAB) m/z: 241 (Mþꢂ1).
HRMS: calcd for C12H17OS2: 241.0721. Found: 241.0707.
4.2.23. 2,2-Diphenyl-1,3-dithiane (1u).22 Prepared according to the
Method B. Recrystallized from AcOEt, colorless prisms, mp
111e112 ꢀC (lit.22 mp 108 ꢀC). IR (neat): 3062, 2892, 1480, 1444,
1282,1035, 930, 890, 864, 737 cmꢂ1. 1H NMR (400 MHz, CDCl3/TMS)
TMS)
d (ppm): 1.12e1.31 (m, 5H), 1.63e1.91 (m, 7H), 2.07e2.14 (m,
1H), 2.79e2.92 (m, 4H), 4.04 (d, J¼5.4 Hz, 1H). 13C{1H} NMR
(100 MHz, CDCl3)
d (ppm): 26.2, 26.2, 26.4, 30.4, 30.9, 43.1, 55.3.
LRMS (EI) m/z: 202 (Mþ). HRMS: calcd for C10H18S2: 202.0850,
d
(ppm): 1.97e2.03 (m, 2H), 2.77e2.80 (m, 4H), 7.24e7.28 (m, 2H),
found: 202.0840.
7.31e7.36 (m, 4H), 7.69e7.71 (m, 4H). 13C{1H} NMR (100 MHz,
CDCl3) d (ppm): 24.5, 29.4, 62.7, 127.5, 128.4, 129.3, 142.5. LRMS (EI)
4.2.17. 2-(2-Phenylethyl)-1,3-dithiane (1o).22 Prepared according to
m/z: 272 (Mþ). HRMS: calcd for C16H16S2: 272.0693, found:
the Method B. Obtained as colorless oil. IR (neat): 3025, 2898, 1602,
272.0683.
1496, 1422, 1274, 1029, 907, 784, 749 cmꢂ1 1H NMR (400 MHz,
.
CDCl3/TMS)
d
(ppm): 1.82e1.92 (m, 1H), 2.05e2.14 (m, 3H),
4.2.24. 2-Methyl-2-phenyl-1,3-dithiane (1v).27 Prepared according
2.81e2.85 (m, 6H), 3.99 (t, J¼7.1 Hz, 1H), 7.20e7.31 (m, 5H). 13C{1H}
to the Method B. Obtained as colorless oil. IR (neat): 2903, 1594,
NMR (100 MHz, CDCl3)
d
(ppm): 26.0, 30.2, 32.5, 36.9, 46.6, 126.1,
1487, 1441, 1275, 1177, 1071, 1026, 906, 762, 698 cmꢂ1 1H NMR
.
128.4, 128.5, 140.9. LRMS (EI) m/z: 224 (Mþ). HRMS: calcd for
(400 MHz, CDCl3/TMS)
d (ppm): 1.80 (s, 3H), 1.93e1.98 (m, 2H),
C12H16S2: 224.0693, found: 224.0684.
2.71e2.75 (m, 4H), 7.24e7.28 (m, 1H), 7.36e7.40 (m, 2H), 7.93e7.96
(m, 2H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 24.6, 28.1, 32.8,
4.2.18. 2-(3-Cyclohexenyl)-1,3-dithiane (1p).2a Prepared according
53.9, 127.0, 127.7, 128.5, 143.8. LRMS (EI) m/z: 210 (Mþ). HRMS:
to the Method A. Obtained as colorless oil. IR (neat): 3020, 2894,
calcd for C11H14S2: 210.0537, found: 210.0535.
2834, 1653, 1421, 1275, 1180, 1043, 908, 763 cmꢂ1 1H NMR
.
(400 MHz, CDCl3/TMS)
1H), 1.96e2.25 (m, 7H), 2.84e2.93 (m, 4H), 4.10 (d, J¼2.9 Hz, 1H),
5.66e5.69 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3)
(ppm): 25.3,
d
(ppm): 1.49e1.58 (m, 1H), 1.84e1.92 (m,
4.2.25. 2-(4-Methoxyphenyl)-2-trimethylsilyl-1,3-dithane
(1w).15 Under an Ar atmosphere, BuLi (3.3 mL, 3.3 mmol, 1.0 M in
hexane) was added to a solution of 2-(4-methoxyphenyl)-1,3-
dithiane (1a) (0.68 g, 3.0 mmol) in THF (7.5 mL) at ꢂ20 ꢀC and
the mixture was stirred for 1 h. Trimethylsilyl chloride (0.32 mL,
3.7 mmol) was slowly added and the whole mixture was gradually
warmed up to 0 ꢀC, then stirred for 1 h. H2O (10 mL) was added and
the mixture was extracted with CHCl3 (30 mLꢁ3). The organic layer
was washed with brine (30 mLꢁ1), dried over MgSO4, and con-
centrated in vacuo. The residue was purified by flash column
chromatography (eluent: hexane) followed by recrystallization
(hexane) to give 2-(4-methoxyphenyl)-2-trimethylsilyl-1,3-
dithiane (1w) (0.34 g, 38%) as a colorless solid. Recrystallized
from hexane, colorless prisms, mp 85e89 ꢀC (lit.15 mp 79.8e81 ꢀC).
IR (neat): 2902, 1605, 1499, 1289, 1241, 1177, 1037, 916, 889,
d
26.3, 26.4, 29.0, 30.6, 30.7, 38.9, 54.2, 125.8, 126.8. LRMS (EI) m/z:
200 (Mþ). HRMS: calcd for C10H16S2: 200.0693, found: 200.0690.
4.2.19. 2-(4-Hydroxymethylphenyl)-1,3-dithiane
(1q). Prepared
according to the Method A. Recrystallized from AcOEt/hexane,
colorless prisms, mp 101e103 ꢀC. IR (neat): 3392, 2893, 2360, 1209,
1112, 1003, 856, 751 cmꢂ1. 1H NMR (400 MHz, CDCl3/TMS)
d (ppm):
1.74 (s, 1H), 1.87e1.99 (m, 1H), 2.14e2.21 (m, 1H), 2.88e2.93 (m,
2H), 3.02e3.10 (m, 2H), 4.67 (s, 2H), 5.16 (s, 1H), 7.33 (d, J¼8.3 Hz,
2H), 7.46 (d, J¼8.3 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm):
25.1, 32.1, 51.1, 64.9, 127.3, 127.7, 138.5, 141.1. LRMS (EI) m/z: 226
(Mþ). HRMS: calcd for C11H14OS2: 226.0486, found: 226.0492.
843 cmꢂ1 1H NMR (400 MHz, CDCl3/TMS)
. d (ppm): 0.06 (s, 9H),
4.2.20. 2-[4-(tert-Butyldiphenylsiloxy)methylphenyl]-1,3-dithiane
(1r). Prepared according to the Method A. Obtained as colorless
1.86e1.92 (m, 1H), 1.97e2.04 (m, 1H), 2.39e2.44 (m, 2H), 2.75e2.82
(m, 2H), 3.83 (s, 3H), 6.90 (d, J¼9.2 Hz, 2H), 7.79 (d, J¼9.2 Hz, 2H).

K. Inamoto et al. / Tetrahedron 69 (2013) 9192e9199
9197
13C{1H} NMR (100 MHz, CDCl3)
d
(ppm): ꢂ3.9, 24.9, 25.2, 46.9, 55.2,
from the above-obtained 2-phenyl-1,3-propanedithiol and p-ani-
saldehyde (0.27 g, 75% over two steps). Recrystallized from AcOEt,
colorless needles, mp 165e167 ꢀC. IR (neat): 2892, 1605, 1509, 1248,
1170, 1022, 851, 818, 767, 725 cmꢂ1. 1H NMR (400 MHz, CDCl3/TMS)
113.6, 130.8, 132.1, 157.3. LRMS (EI) m/z: 298 (Mþ). HRMS: calcd for
C14H22OS2Si 298.0881, found: 298.0867.
4.2.26. 2-Methyl-2-(2-phenylethyl)-1,3-dithiane
according to the Method B. Obtained as yellowish oil. IR (neat):
3025, 2905, 1602, 1497, 1422, 1370, 1275, 1057, 907, 748 cmꢂ1 1H
NMR (400 MHz, CDCl3/TMS) (ppm): 1.68 (s, 3H), 1.93e2.03 (m,
2H), 2.21e2.25 (m, 2H), 2.78e2.94 (m, 6H), 7.18e7.23 (m, 3H),
7.28e7.32 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3)
(ppm): 25.2,
(1x).28 Prepared
d (ppm): 2.92e2.96 (m, 2H), 3.16e3.30 (m, 3H), 3.80 (s, 3H), 5.22 (s,
1H), 6.88 (d, J¼8.8 Hz, 2H), 7.22e7.27 (m, 3H), 7.32e7.36 (m, 2H),
.
7.44 (d, J¼8.8 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 38.3,
d
42.8, 50.4, 44.3, 114.2, 126.7, 127.1, 128.87, 128.92, 130.3, 144.9, 159.7.
LRMS (EI) m/z: 302 (Mþ). HRMS: calcd for C17H18OS2: 302.0799,
found: 302.0780.
d
26.5, 27.8, 31.2, 43.4, 48.9, 125.9, 128.5 (2C), 141.8. LRMS (EI) m/z:
238 (Mþ). HRMS: calcd for C13H18S2: 238.0850, found: 238.0833.
4.3. Deprotection of 1,3-dithianes
4.2.27. 1,5-Dithiaspiro[5.5]undecane (1y). Prepared according to
the Method A. Recrystallized from hexane, colorless plates, mp
39e41 ꢀC. IR (neat): 3753, 2972, 2850, 2360, 1653, 1559, 1419, 1269,
4.3.1. Representative procedure for deprotection of 1,3-dithianes
(Table 2, entry 3). A mixture of 2-(2-methoxyphenyl)-1,3-dithiane
(1c) (0.11 g, 0.50 mmol), 1,4-benzoquinone (64.8 mg, 0.60 mmol),
and NaI (0.70 mg, 0.005 mmol) in MeCN (2 mL) and H2O (0.2 mL)
was stirred at 100 ꢀC for 24 h. The reaction mixture was filtered
through a pad of Celite and the filtrate was concentrated in vacuo.
The residue was purified by flash column chromatography (eluent:
hexane/AcOEt¼15/1) to give 2-methoxybenzaldehyde (2c, 66.5 mg,
98%) as colorless oil.
1130, 1010, 758 cmꢂ1
.
1H NMR (400 MHz, CDCl3/TMS)
d
(ppm):
1.43e1.49 (m, 2H), 1.60e1.66 (m, 4H), 1.96e2.01 (m, 6H), 2.78e2.82
(m, 4H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 22.0, 25.8, 25.9,
26.1, 37.9, 50.3. LRMS (EI) m/z: 188 (Mþ). HRMS: calcd for C9H16S2:
188.0693, found: 188.0685.
4.2.28. 9-tert-Butyl-1,5-dithiaspiro[5.5]undecane
(1z). Prepared
according to the Method B. Recrystallized from hexane, colorless
4.3.2. 4-Methoxybenzaldehyde (2a). Obtained as colorless oil. IR
prisms, mp 71e72 ꢀC. IR (neat): 2940, 2843, 1444, 1361, 1280, 1242,
(neat): 2840, 2739, 1679, 1595, 1425, 1314, 1255, 1156, 1021, 829,
1023, 1005, 910, 787 cmꢂ1. 1H NMR (400 MHz, CDCl3/TMS)
d
(ppm):
758 cmꢂ1.1HNMR(400 MHz,CDCl3/TMS)
d(ppm): 3.90 (s, 3H), 7.01 (d,
0.86 (s, 9H), 0.99e1.06 (m, 1H), 1.43e1.68 (m, 6H), 1.95e2.01 (m,
J¼8.8 Hz, 2H), 7.85 (d, J¼8.8 Hz, 2H), 9.89 (s, 1H). 13C{1H} NMR
2H), 2.36e2.41 (m, 2H), 2.72e2.75 (m, 2H), 2.87e2.89 (m, 2H). 13C
(100 MHz, CDCl3) d (ppm): 55.5, 114.3,130.0, 131.9,164.6, 190.8. LRMS
{1H} NMR (100 MHz, CDCl3)
d
(ppm): 22.9, 25.7, 26.2, 26.3, 27.5,
(EI) m/z:136(Mþ). HRMS:calcdforC8H8O:136.0524,found:136.0545.
32.4, 38.4, 48.0, 50.2. LRMS (EI) m/z: 244 (Mþ). HRMS: calcd for
C13H24S2: 244.1319, found: 244.1304.
4.3.3. 3-Methoxybenzaldehyde (2b). Obtained as colorless oil. IR
(neat): 2839, 2729, 1699, 1586, 1485, 1261, 1148, 1037, 785,
4.2.29. 2-(4-Methoxyphenyl)-5-phenyl-1,3-dithiane (1aa). Under
an Ar atmosphere, diethyl phenylmalonate (4.5 g, 19.0 mmol) was
added dropwise to a solution of LiAlH4 (1.9 g, 50.0 mmol) in THF
(90 mL) at 0 ꢀC. The reaction mixture was warmed up to room
temperature and stirred overnight. After the addition of Na2SO4,
the mixture was extracted with AcOEt (30 mLꢁ3) and the com-
bined organic layer was washed with H2O (50 mLꢁ2) and brine
(50 mLꢁ1). The organic layer was dried over Na2SO4 and concen-
trated in vacuo. The residue was purified by flash column chro-
matography (eluent: hexane/AcOEt¼1:3) to give 2-phenyl-1,3-
propanediol (0.85 g, 28%) as colorless oil. Under an Ar atmo-
sphere, a solution of p-toluenesulfonyl chloride (6.0 g, 31.5 mmol)
in MeCN (16 mL) was added dropwise to a solution of 2-phenyl-1,3-
propanediol (1.6 g, 10.5 mmol), Me3N$HCl (0.20 g, 2.1 mmol), and
Et3N (3.2 g, 31.5 mmol) in MeCN (7 mL) at 0 ꢀC and stirred for 5 h at
the same temperature. After the addition of N,N0-dimethylethyle-
nediamine (2 mL), the mixture was extracted with AcOEt
(30 mLꢁ3) and the combined organic layer was washed with H2O
(50 mLꢁ2) and brine (50 mLꢁ1). The organic layer was dried over
Na2SO4 and concentrated in vacuo. The residue was purified by
flash column chromatography (eluent: hexane/AcOEt¼3:1) to give
2-phenyl-1,3-propaneditosylate (0.88 g, 18%) as a colorless solid.
Under an Ar atmosphere, thiourea (1.4 g, 19.0 mmol) was added to
a solution of 2-phenyl-1,3-propaneditosylate (0.88 g, 1.9 mmol) in
EtOH (10 mL) at room temperature, and the mixture was heated
under reflux overnight. After the reaction mixture was cooled down
to room temperature, 20% NaOH (10 mL) was added and the whole
mixture was heated under reflux overnight. After the addition of
1 M HCl (30 mL), the mixture was extracted with CH2Cl2 (50 mLꢁ3)
and the combined organic layer was washed with H2O (50 mLꢁ1)
and brine (50 mLꢁ1). The organic layer was dried over MgSO4 and
concentrated in vacuo to give 2-phenyl-1,3-propanedithiol (0.48 g)
as yellowish oil, which was used to the next reaction without fur-
ther purification. According to the Method A, 1aa was prepared
737 cmꢂ1
.
1H NMR (400 MHz, CDCl3/TMS)
d
(ppm): 3.87 (s, 3H),
7.17e7.21 (m,1H), 7.39e7.40 (m, 1H), 7.45e7.47 (m, 2H), 9.98 (s, 1H).
13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 55.4, 112.0, 121.5, 123.5,
130.0, 137.8, 160.1, 192.1. LRMS (EI) m/z: 136 (Mþ). HRMS: calcd for
C8H8O2: 136.0524, found: 136.0505.
4.3.4. 2-Methoxybenzaldehyde (2c). Obtained as colorless oil. IR
(neat): 2843, 1683, 1597, 1484, 1394, 1285, 1242, 1160, 1021, 834,
733 cmꢂ1
.
1H NMR (400 MHz, CDCl3/TMS)
d
(ppm): 3.93 (s, 3H),
6.98e7.05 (m, 2H), 7.55 (t, J¼7.8 Hz,1H), 7.83 (d, J¼7.8 Hz, 1H), 10.48
(s, 1H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 55.6, 111.6, 120.6,
124.8, 128.5, 135.9, 161.8, 189.8. LRMS (EI) m/z: 136 (Mþ). HRMS:
calcd for C8H8O2: 136.0524, found: 136.0511.
4.3.5. 4-Cyanobenzaldehyde (2d). Recrystallized from AcOEt/hex-
ane, colorless needles, mp 97e99 ꢀC. IR (neat): 2846, 2229, 1701,
1607, 1387, 1296, 1202, 1172, 826, 737 cmꢂ1 1H NMR (400 MHz,
.
CDCl3/TMS)
d
(ppm): 7.86 (d, J¼8.3 Hz, 2H), 8.01 (d, J¼8.3 Hz, 2H),
10.11 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 117.5, 117.6,
129.8, 132.8, 138.7, 190.6. LRMS (EI) m/z: 131 (Mþ). HRMS: calcd for
C8H5NO: 131.0371, found: 131.0555.
4.3.6. 4-Nitrobenzaldehyde (2e). Recrystallized from AcOEt/hex-
ane, yellowish prisms, mp 107e109 ꢀC. IR (neat): 2851, 1701, 1540,
1340, 1195, 1103, 1007, 849, 813, 738, 677 cmꢂ1. 1H NMR (400 MHz,
CDCl3/TMS)
d
(ppm): 8.11 (d, J¼8.8 Hz, 2H), 8.41 (d, J¼8.8 Hz, 2H),
10.19 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 124.1, 130.3,
139.9, 150.9, 190.2. LRMS (EI) m/z: 151 (Mþ). HRMS: calcd for
C7H5NO3: 151.0269, found: 151.0279.
4.3.7. 4-(Methoxycarbonyl)benzaldehyde (2f). Recrystallized from
AcOEt, colorless prisms, mp 60e62 ꢀC. IR (neat): 1720, 1683, 1576,
1432, 1278, 1194, 1105, 851, 807, 755, 681 cmꢂ1. 1H NMR (400 MHz,
CDCl3/TMS)
d
(ppm): 3.96 (s, 3H), 7.95 (d, J¼8.3 Hz, 2H), 8.17 (d,

9198
K. Inamoto et al. / Tetrahedron 69 (2013) 9192e9199
J¼8.3 Hz, 2H), 10.10 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3)
d
(ppm):
NMR (400 MHz, CDCl3/TMS)
d
(ppm): 2.77 (td, J1¼7.8 Hz, J2¼1.0 Hz,
52.3, 129.2, 129.9, 134.8, 138.9, 165.7, 191.4. LRMS (EI) m/z: 164 (Mþ).
2H), 2.95 (t, J¼7.8 Hz, 2H), 7.18e7.22 (m, 3H), 7.27e7.31 (m, 2H),
HRMS: calcd for C9H8O3: 164.0473, found: 164.0496.
9.81 (t, J¼1.4 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 28.1,
45.2, 126.3, 128.2, 128.6, 140.3, 201.5. LRMS (EI) m/z: 134 (Mþ).
4.3.8. 4-Chlorobenzaldehyde (2g). Recrystallized from AcOEt, col-
orless needles, mp 47e48 ꢀC. IR (neat): 1684,1590,1424,1282,1253,
HRMS: calcd for C9H10O: 134.0732, found: 134.0725.
1169, 1090, 1015, 818, 739, 681 cmꢂ1
.
1H NMR (400 MHz, CDCl3/
4.3.17. 3-Cyclohexene-1-carboxaldehyde (2p). Because of the vola-
tility of the product, the yield was determined by GC analysis versus
a calibrated internal standard.
TMS)
d
(ppm): 7.50 (d, J¼7.8 Hz, 2H), 7.82 (d, J¼7.8 Hz, 2H), 9.98 (s,
1H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 129.2, 130.7, 134.6,
140.7, 190.6. LRMS (EI) m/z: 140 (Mþ). HRMS: calcd for C7H535ClO:
140.0029, found: 140.0019.
4.3.18. 4-Hydroxymethybenzaldehyde (2q). Recrystallized from
AcOEt/hexane, colorless prisms, mp 39e40 ꢀC. IR (neat): 3356, 2841,
4.3.9. 4-Bromobenzaldehyde (2h). Recrystallized from AcOEt/hex-
ane, colorless prisms, mp 58e59 ꢀC. IR (neat): 2860, 1686, 1587,
1573, 1480, 1384, 1205, 1066, 1009, 809 cmꢂ1. 1H NMR (400 MHz,
2375, 1689, 1608, 1205, 1012, 825, 769 cmꢂ1 1H NMR (400 MHz,
.
CDCl3/TMS)
d
(ppm): 2.47 (s, 1H), 4.79 (s, 2H), 7.52 (d, J¼8.1 Hz, 2H),
7.85 (d, J¼8.1 Hz, 2H), 9.97 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3)
CDCl3/TMS)
d
(ppm): 7.68 (d, J¼8.8 Hz, 2H), 7.75 (d, J¼8.8 Hz, 2H),
d (ppm): 64.4, 126.9, 130.0, 135.6, 147.9, 192.1. LRMS (EI) m/z: 136
9.97 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3)
d
(ppm): 129.7, 130.9,
(Mþ). HRMS: calcd for C8H8O2: 136.0524, found: 136.0508.
132.4, 135.1, 191.0. LRMS (EI) m/z: 184 (Mþ). HRMS: calcd for
C7H579BrO: 183.9524, found: 183.9529.
4.3.19. 4-(tert-Butyldiphenylsiloxy)methylbenzaldehyde
(2r). Obtained as colorless oil. IR (neat): 2963, 2857, 2362, 1696,
4.3.10. 2-Iodobenzaldehyde (2i). Recrystallized from AcOEt/hexane,
colorless needles, mp 37e38 ꢀC. IR (neat): 2938, 2924, 1490, 1453,
1610, 1426, 1214, 1105, 1078, 812, 739 cmꢂ1 1H NMR (400 MHz,
.
CDCl3/TMS)
(d, J¼8.3 Hz, 2H), 7.58e7.61 (m, 4H), 7.75 (d, J¼8.3 Hz, 2H), 9.90 (s,
1H). 13C{1H} NMR (100 MHz, CDCl3)
(ppm): 19.3, 26.8, 65.1, 126.2,
d (ppm): 1.03 (s, 9H), 4.74 (s, 2H), 7.26e7.36 (m, 6H), 7.41
1221, 1207, 1027, 970, 770, 712 cmꢂ1 1H NMR (400 MHz, CDCl3/
.
TMS)
d
(ppm): 7.29 (td, J1¼7.8 Hz, J2¼1.5 Hz, 1H), 7.47 (t, J¼7.8 Hz,
d
1H), 7.88 (dd, J1¼7.8 Hz, J2¼1.5 Hz, 1H), 7.96 (d, J¼7.8 Hz, 1H), 10.07
127.8, 129.79, 127.84, 133.1, 135.3, 135.46, 135.45, 191.9. LRMS (EI) m/
(s, 1H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 100.6, 128.7, 130.2,
z: 374 (Mþ). HRMS: calcd for C24H26O2Si: 374.1702, found: 374.1675.
135.1, 135.4, 140.6, 195.7. LRMS (EI) m/z: 232 (Mþ). HRMS: calcd for
C7H5IO: 231.9385, found: 231.9369.
4.3.20. Benzophenone (2u). Recrystallized from hexane, colorless
prisms, mp 47e49 ꢀC. IR (neat): 3059, 1656, 1598, 1447, 1275, 1176,
4.3.11. 4-Hydroxybenzaldehyde (2j). Recrystallized from AcOEt,
brownish plates, mp 113e119 ꢀC. IR (neat): 3159, 1669, 1559, 1457,
941, 918, 810, 763 cmꢂ1. 1H NMR (400 MHz, CDCl3/TMS)
d (ppm):
7.45 (t, J¼7.6 Hz, 4H), 7.56 (t, J¼7.6 Hz, 2H), 7.79 (d, J¼7.6 Hz, 4H). 13C
1288, 1217, 1161, 1113, 832, 699 cmꢂ1
.
1H NMR (400 MHz, CDCl3/
{1H} NMR (100 MHz, CDCl3)
d (ppm): 128.2, 129.9, 132.3, 137.5,
TMS)
d
(ppm): 6.02 (s, 1H), 6.97 (d, J¼8.6 Hz, 2H), 7.82 (d, J¼8.6 Hz,
196.5. LRMS (EI) m/z: 182 (Mþ). HRMS: calcd for C13H10O: 182.0732,
2H), 9.86 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3)
d
(ppm): 116.0,
found: 182.0718.
130.0, 132.5, 161.4, 191.1. LRMS (EI) m/z: 122 (Mþ). HRMS: calcd for
C7H6O2: 122.0368, found: 122.0362.
4.3.21. Acetophenone (2v). Obtained as colorless oil. IR (neat):
3062, 1680, 1598, 1449, 1357, 1263, 1180, 1024, 954, 757, 687 cmꢂ1
.
4.3.12. Piperonal (2k). Obtained as colorless oil. IR (neat): 2919,
1H NMR (400 MHz, CDCl3/TMS)
d (ppm): 2.61 (s, 3H), 7.44e7.48 (m,
1794, 1671, 1600, 1446, 1253, 1034, 929, 811, 784 cmꢂ1 1H NMR
.
2H), 7.54e7.58 (m, 1H), 7.94e7.97 (m, 2H). 13C{1H} NMR (100 MHz,
(400 MHz, CDCl3/TMS)
d
(ppm): 6.08 (s, 2H), 6.94 (d, J¼7.8 Hz, 1H),
CDCl3) d (ppm): 26.6, 128.3, 128.5, 133.1, 137.1, 198.1. LRMS (EI) m/z:
7.34 (d, J¼1.5 Hz,1H), 7.42 (dd, J1¼7.8 Hz, J2¼1.5 Hz, 1H), 9.81 (s, 1H).
120 (Mþ). HRMS: calcd for C8H8O: 120.0575, found: 120.0559.
13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 102.1, 106.9, 108.3, 128.7,
131.8, 148.7, 153.1, 190.3. LRMS (EI) m/z: 150 (Mþ). HRMS: calcd for
4.3.22. (4-Methoxybenzoyl)trimethylsilane (2w). Obtained as yel-
C8H6O3: 150.0317, found: 150.0301.
lowish oil. IR (neat): 2960, 1584, 1564, 1506, 1305, 1250, 1218, 1161,
1029, 834 cmꢂ1. 1H NMR (400 MHz, CDCl3/TMS)
d (ppm): 0.36 (s,
4.3.13. 2-Naphthaldehyde (2l). Recrystallized from hexane, color-
less prisms, mp 63e64 ꢀC. IR (neat): 3062, 2831, 1689, 1460, 1344,
9H), 3.87 (s, 3H), 6.96 (d, J¼8.3 Hz, 2H), 7.84 (d, J¼8.3 Hz, 2H). 13C
{1H} NMR (100 MHz, CDCl3)
d
(ppm): ꢂ1.27, 55.4, 113.7, 129.8, 135.2,
1257, 1165, 1118, 835, 749 cmꢂ1
.
1H NMR (400 MHz, CDCl3/TMS)
163.1, 232.9. LRMS (EI) m/z: 208 (Mþ). HRMS: calcd for C11H16O2Si:
d
(ppm): 7.56e7.66 (m, 2H), 7.88e8.00 (m, 4H), 8.32 (s, 1H), 10.15 (s,
208.0920, found: 208.0877.
1H). 13C{1H} NMR (100 MHz, CDCl3)
d
(ppm): 122.7, 127.0, 128.0,
129.0, 129.1, 129.5, 132.6, 134.1, 134.5, 136.4, 192.2. LRMS (EI) m/z:
4.3.23. Benzylacetone (2x). Obtained as colorless oil. IR (neat):
156 (Mþ). HRMS: calcd for C11H8O: 156.0575, found: 156.0552.
3027, 1715, 1602, 1497, 1453, 1356, 1161, 1080, 1031, 748 cmꢂ1 1H
.
NMR (400 MHz, CDCl3/TMS)
d
(ppm): 2.13 (s, 3H), 2.75 (t, J¼7.8 Hz,
4.3.14. 2-Thiophenecarboxaldehyde (2m). Obtained as yellow oil. IR
2H), 2.89 (t, J¼7.8 Hz, 2H), 7.16e7.20 (m, 3H), 7.25e7.29 (m, 2H). 13C
(neat): 3090, 2821, 2361, 1654, 1513, 1417, 1212, 1045, 863, 723 cmꢂ1
.
{1H} NMR (100 MHz, CDCl3)
d (ppm): 29.7, 30.0, 45.1, 126.0, 128.2,
1H NMR (400 MHz, CDCl3/TMS)
d
(ppm): 7.22 (dd, J1¼4.8 Hz,
128.4, 140.9, 207.8. LRMS (EI) m/z: 148 (Mþ). HRMS: calcd for
J2¼3.2 Hz 1H), 7.77e7.80 (m, 2H), 9.96 (s, 1H). 13C{1H} NMR
C10H12O: 148.0888, found: 148.0885.
(100 MHz, CDCl3) d (ppm): 128.3, 135.1, 136.2, 144.0, 182.9. LRMS (EI)
m/z: 111 (Mþ). HRMS: calcd for C5H4OS: 111.9983, found: 111.9934.
4.3.24. Cyclohexanone (2y). Because of the volatility of the product,
the yield was determined by GC analysis versus a calibrated in-
ternal standard.
4.3.15. Cyclohexanecarboxaldehyde (2n). Because of the volatility of
the product, the yield was determined by GC analysis versus
a calibrated internal standard.
4.3.25. 4-tert-Butylcyclohexanone (2z). Recrystallized from hexane,
colorless prisms, mp 46e48 ꢀC. IR (neat): 2946, 2866, 1723, 1366,
4.3.16. 3-Phenylpropanal (2o). Obtained as colorless oil. IR (neat):
1333, 1223, 1161, 984, 942, 777 cmꢂ1 1H NMR (400 MHz, CDCl3/
.
3028, 2726, 1723, 1603, 1497, 1453, 1389, 1030, 854, 744 cmꢂ1
.
1H
TMS) d (ppm): 0.88 (s, 9H), 1.35e1.46 (m, 3H), 2.03e2.06 (m, 2H),

K. Inamoto et al. / Tetrahedron 69 (2013) 9192e9199
9199
2.23e2.38 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3)
d (ppm): 27.5,
4. Tanemura, K.; Dohya, H.; Imamura, M.; Suzuki, T.; Horaguchi, T. J. Chem. Soc.,
Perkin Trans. 1 1996, 453e457.
5. Nicolaou, K. C.; Mathison, C. J. N.; Montagnon, T. Angew. Chem., Int. Ed. 2003, 42,
32.4, 41.2, 46.7, 212.4. LRMS (EI) m/z: 154 (Mþ). HRMS: calcd for
C10H18O: 154.1358, found: 154.1358.
4077e4082.
6. Garbaccio, R. M.; Stachel, S. J.; Baechlin, D. K.; Danishefsky, S. J. J. Am. Chem. Soc.
2001, 123, 10903e10908.
7. Corey, E. J.; Erickson, B. W. J. Org. Chem. 1971, 36, 3553e3560.
8. Mondal, E.; Bose, G.; Sahu, P. R.; Khan, A. T. Chem. Lett. 2001, 30, 1158e1159.
9. Desai, U. V.; Pore, D. M.; Tamhankar, B. V.; Jadhav, S. A.; Wadgaonkar, P. P.
Tetrahedron Lett. 2006, 47, 8559e8561.
10. (a) Kirihara, M.; Harano, A.; Tsukiji, H.; Takizawa, R.; Uchiyama, T.; Hatano, A.
Tetrahedron Lett. 2005, 46, 6377e6380; (b) Kirihara, M.; Noguchi, T.; Okajima,
N.; Naito, S.; Ishizuka, Y.; Harano, A.; Tsukiji, H.; Takizawa, R. Tetrahedron Lett.
2012, 68, 1515e1520.
4.3.26. 4-Phenyl-1,2-dithiolane (5).29 Recrystallized from hexane,
yellowish plates, mp 84e85 ꢀC (lit.28 mp 82e84 ꢀC). IR (neat): 2850,
1747, 1684, 1579, 1390, 1263, 1202, 1017, 822, 750 cmꢂ1 1H NMR
.
(400 MHz, CDCl3/TMS)
d (ppm): 3.20e3.25 (m, 2H), 3.50e3.54 (m,
2H), 3.63e3.71 (m, 1H), 7.24e7.36 (m, 5H). 13C{1H} NMR (100 MHz,
CDCl3) d (ppm): 45.9, 53.1, 127.28, 127.29, 128.8, 141.5. LRMS (EI) m/
z: 182 (Mþ). HRMS: calcd for C9H10S2: 182.0224, found: 182.0240.
11. For other selected recent examples of deprotection of dithioacetals, see: (a)
Moghaddam, F. M.; Boeini, H. Z.; Zargarani, D.; Bardajee, G. R. Synth. Commun.
ꢁꢀꢁ
2006, 36, 1093e1096; (b) Oksdath-Mansilla, G.; Penenory, A. B. Tetrahedron Lett.
Acknowledgements
2007, 48, 6150e6154; (c) Wang, E.-C.; Wu, C.-H.; Chien, S.-C.; Chiang, W.-C.;
Kuo, Y.-H. Tetrahedron Lett. 2007, 48, 7706e7708; (d) Ganguly, N. C.; Barik, S. K.
Synthesis 2009, 1393e1399; (e) Bahrami, K.; Khodaei, M. M.; Tajik, M.; Shaki-
baian, V. Chin. Chem. Lett. 2012, 23, 81e85.
This work was partly supported by a Grant-in-Aid for Scientific
Research (B) (No. 23390002), a Grant-in-Aid for Scientific Research
(C) (No. 25460002), and a Grant-in-Aid for Challenging Exploratory
Research (No. 25670002) from Japan Society for the Promotion of
Science, and a Grant-in-Aid for Scientific Research on Innovative
Areas ‘Advanced Molecular Transformations by Organocatalysts’
(No. 23105009) from The Ministry of Education, Culture, Sports,
Science and Technology, Japan.
12. Compound 3 was completely consumed in this case and a complex mixture of
several unknown compounds was obtained, although the characterization of
such byproducts was unfortunately failed.
13. Moghaddam, F. M.; Bardajee, G. R.; Osuki, A. A. Phosphorus, Sulfur Silicon Relat.
Elem. 2006, 181, 1445e1450.
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17. DeMartino, J. K.; Hwang, I.; Connelly, S.; Wilson, I. A.; Boger, D. L. J. Med. Chem.
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Supplementary data
1H NMR and 13C NMR spectra for compounds 1 and 2 are
available. Supplementary data related to this article can be found at
http://dx.doi.org/10.1016/j.tet.2013.08.061.
18. Page, P. C. B.; Wilkes, R. D.; Namwindwwa, E. S.; Witty, M. J. Tetrahedron 1995,
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