Visible-Light Photoredox-Catalyzed Thioacetalization of Aldehydes Under Metal-Free and Solvent-Free Conditions

Article abstract of DOI:10.1002/adsc.201800999

A first visible-light photoredox-catalyzed thioacetalization of aldehydes under metal-free and solvent-free conditions is described. Under blue LED irradiation, a reactive thiyl radical was initially generated through single-electron oxidation of thiol, w

Full text of DOI:10.1002/adsc.201800999

Title: Visible-Light Photoredox-Catalyzed Thioacetalization of
Aldehydes Under Metal-Free and Solvent-Free Conditions
Authors: Kai Du, Shao-Chien Wang, R. Sidick Basha, and Chin-Fa Lee
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201800999
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10.1002/adsc.201800999
Advanced Synthesis & Catalysis
VERY IMPORTANT PUBLICATION
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Visible-Light Photoredox-Catalyzed Thioacetalization of
Aldehydes Under Metal-Free and Solvent-Free Conditions
Kai Du,a Shao-Chien Wang,a R. Sidick Basha,a and Chin-Fa Lee*a,b,c
a Department of Chemistry, National Chung Hsing University, Taichung, Taiwan 402, R.O.C
bResearch Center for Sustainable Energy and Nanotechnology (RCSEN)
c Innovation and Development Center of Sustainable Agriculture (IDCSA)
Tel: +886 4 2284-0411 ext. 810; Fax: +886 4 2286-2547; E-mail: cfalee@dragon.nchu.edu.tw
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract.
A
first visible-light photoredox-catalyzed conditions, and a wide range of acyclic and cyclic
thioacetalization of aldehydes under metal-free and solvent- dithioacetal derivatives were afforded in good to excellent
free conditions is described. Under blue LED irradiation, a yields.
reactive thiyl radical was initially generated through single-
electron oxidation of thiol, which subsequently reacted with
Keywords: Thioacetalization; Radical reaction;
Photocatalyst; Aldehyde; Thiol
aldehydes to afford dithioacetals following
mechanism. The reaction proceeded under ambient
a radical
Introduction
Organosulfur compounds are important molecules
used for major structural diversification in drug
discovery,[1]
pharmaceuticals,[2]
and
material
science.[3] These sulfur-containing precursors are
used as key intermediates in total synthesis of natural
products[4] and diverse synthetic modifications.[5] In
particular, dithioacetals act as the prominent
protecting group for carbonyl moieties of aldehydes
or ketones; they also function as equivalent acyl
anions for specific chemical transformations.[6]
Dithioacetals have been used as precursors in
fluorination,[7a] hydrogenolysis,[7b] alkylation,[7c,d] and
olefination[7e]. Recently, dithioacetals were also
utilized in C–H or C–S bond activation,[8a,b]
hydrodesulfurization,[8c] autoxidation,[9] and dynamic
library access of dithioacetals.[10] Various synthetic
approaches, including metal-catalyzed reactions,[11]
Brønsted or Lewis acid-mediated reactions,[12] solid-
supported-linker[13a] or resin-bounded–solid-phase
reactions,[13b] and HBA-UV irradiation reactions,[14]
can be used for thioacetalization of aldehydes
(Scheme 1a); however, these methods can often be
toxic and hazardous, have limited substrate scope and
side-product–related issues, and require harsh
reaction conditions. Therefore, establishing a facile
methodology for thioacetalization of aldehydes
remains challenging and requires further development.
Scheme 1. Reaction design, activation, and pathways
because of its mildness and high functional group
tolerance in the development of organic
methodologies.[15] It acts as a single-electron transfer
(SET) system that prevents undesired reaction
Moreover,
visible-light–promoted
photoredox
catalysis has recently received considerable attention
1
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10.1002/adsc.201800999
Advanced Synthesis & Catalysis
pathways, to accomplish simple and clean organic
transformation processes,[16] and its homogenous
nature increases the catalyst efficiency with the
lowest catalyst loading in the reaction system.
Table 1. Optimization of reaction conditions[a]
Visible-light–driven reactions have emerged as
versatile methods for C–S bond formation.[17] Lei et
al.[18] developed visible-light-promoted acetalization
of aldehydes with alcohols through the photoacid-
mediated nucleophilic addition pathway (Scheme 1b).
We envisioned that photoredox catalysis with
uniform blue light penetration may activate thiol
through SET to enable radical addition on
aldehyde[19] to access dithioacetals. As part of our
ongoing progress in the field of C–S bond coupling
reaction,[20] herein we report an environment friendly
thioacetalization of aldehydes with thiols through
visible-light–driven eosin Y-catalyzed C–S bond
formation at ambient temperature under metal-free
and solvent-free conditions (Scheme 1c).
Results and Discussion
Entry Photocatalyst
Yield of 3a[b]
1[c]
2[c]
3
3 mol% Ir(ppy)3
58
73
99
95
48
65
75
For optimization, benzaldehyde (1a) and 1-
dodecanethiol (2a) were selected as model substrates
under solvent-free conditions, and the reaction was
initially carried out using 3.0 mol% photoredox
catalysts Ir(ppy)3 and Ru(bpy)3Cl2 with 10-W blue
LEDs, which provided the desired product
dithioacetal, 3a, in 58% and 73% yields, respectively
(Table 1, entries 1 and 2). Notably, when 0.1 mol%
eosin Y was employed as an organic photocatalyst,
the product was obtained in 99% yield (Table 1, entry
3). Other organo photocatalysts, such as eosin B, rose
3 mol% Ru(bpy)3Cl2
0.1 mol% Eosin Y
4
0.1 mol% Eosin B
5
0.1 mol% Rose Bengal
-
6
7
0.1 mol% Acr-Mes+ClO4
0.1 mol% Methylene blue
[a]Reaction conditions: 1a (1.0 mmol), 2a (2.2 mmol),
photocatalyst (3 mol% for entries 1 and 2 and 0.1 mol%
for entries 3–7), 10-W blue LEDs. [b]Isolated yields.
[c]Reaction carried out with 1a (0.5 mmol) and 2a (1.1
mmol).
−
bengal, Acr-Mes+ClO4 , and methylene blue, were
also screened (Table 1, entries 4–7); nevertheless,
eosin
Y
is the best among those organo
photocatalysts for thioacetalization of benzaldehyde
(Table 1, entry 3).
3o in 99% yield. 3,5-Disubstituted and 2,3,5-
trisubstituted benzaldehydes reacted smoothly with
2a and the corresponding products 3p and 3q were
obtained in 95% and 74% yields, respectively.
Heteroaldehydes were also found to be compatible
with the optimized reaction conditions, delivering the
products 3r and 3s in 77% and 98% yields,
respectively. Other aldehydes, such as 1-
naphthaldehyde and cinnamaldehyde, reacted with 2a
and provided the products 3t and 3u in 99% and 71%
yields, respectively.
To study the substrate scope for this notable
metal-free,
visible-light
photoredox-catalyzed
thioacetalization, various aldehydes 1a–u were
employed for the reaction with thiol 2a under
optimized reaction conditions (Table 2). 2-
Bromobenzaldehyde
afforded dithioacetals 3b and 3c in 85% yield.
Similarly, 2-chlorobenzaldehyde or 3-
chlorobenzaldehyde afforded 3d and 3e in 81% yield.
Electron-rich aldehydes, such as 2-
or
4-bromobenzaldehyde
Next, we screened different thiols 2b–d for
thioacetalization with different aldehydes under
optimized reaction conditions (Table 3). We began
our studies with the reaction of cyclohexanethiol (2b)
with benzaldehyde, 2-tolualdehyde, and 4-
methoxybenzaldehyde under identical reaction
conditions, which provided the corresponding
dithioacetals 4a–c in quantitative yields. 2-
Butanethiol (2c) also reacted well with benzaldehyde
to afford the desired product 4d in 99% yield.
However, thiophenol (2d) on reaction with 4-
methoxybenzaldehyde could only provide the desired
product 4e in 30% yield.
methoxybenzaldehyde or 4-methoxybenzaldehyde,
were superior to other aldehydes and afforded
dithioacetals 3f and 3g in 96% yield. Different
tolualdehydes reacted well under the optimized
reaction conditions to provide the resulting
dithioacetals 3h–j in 76%–99% yields. Electron-
deficient aldehydes, namely 2-nitrobenzaldehyde, 3-
nitrobenzaldehyde, and 4-nitrobenzaldehyde, also
reacted well with thiol 2a to provide the products 3k–
m
in relatively good yields (52%–78%). 3-
Formylbenzonitrile also tolerated the reaction
conditions well and afforded the product 3n in 73%
yield. Salicylaldehyde reacted well with 2a to provide
2
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10.1002/adsc.201800999
Advanced Synthesis & Catalysis
Table 3. Scope of various thiols with aromatic aldehydes[a]
Table 2. Scope of aldehydes with 2a[a]
[a]Reaction conditions: 1 (1.0 mmol), 2 (2.2 mmol), eosin Y
(0.1 mol%), 10-W blue LEDs. [b]Isolated yields.
Table 4. Synthesis of cyclic dithioacetals 5[a],[b]
[a]Reaction conditions: 1 (1.0 mmol), 2 (1.1 mmol), eosin Y
(0.1 mol%), 10-W blue LEDs. [b]Isolated yields.
[a]Reaction conditions: 1 (1.0 mmol), 2 (2.2 mmol), eosin Y
(0.1 mol%), 10-W blue LEDs. [b]Isolated yields.
Next, dithiols 2e and 2f were tested for
thioacetalization with different aldehydes under
optimized reaction conditions. They provided the
cyclic dithioacetal products 5a–5d in 35%–81%
yields (Table 4). However, alkyl aldehydes do not
work well in the present system; for example, when
butyraldehyde and thiophenol were exposed to the
standard reaction conditions, no product was detected.
On the other hand, only a trace amount of product
was observed when the reaction was performed by
using butyraldehyde and cyclohexanethiol as the
starting materials.
We also investigated the reaction efficiency
at a larger scale by conducting a 10-g scale
reaction between 1a and 2a in the presence of 0.1
mol% eosin Y under standard reaction conditions.
The desired product 3a was obtained in excellent
yield (Scheme 2).
Scheme 2. Ten-gram scale synthesis of dithioacetal
To propose a plausible reaction mechanism of
this
visible-light
photoredox-catalyzed
thioacetalization, various control experiments were
performed (Scheme 3). In the absence of blue-light
irradiation, 3a was not formed. Therefore, light
radiation is necessary to carry out this transformation
(Scheme 3a). In the presence of one equivalent of the
radical inhibitor TEMPO, the reaction failed to
deliver the product 4a, indicating that the reaction
proceeds through a radical pathway (Scheme 3b).
This experiment also ruled out the hypothesis of a
photoacid-mediated pathway and acid-catalyzed
pathway (released from the oxidation of thiol to a
thiyl radical). In addition, on reaction with thiol 2g
under standard reaction conditions in the presence of
TEMPO,
the
thiyl
radical
adduct,
1-
((isobutylthio)oxy)-2,2,6,6-tetramethyl piperidine 6,
3
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10.1002/adsc.201800999
Advanced Synthesis & Catalysis
was formed, which was detected through GC–MS
(Scheme 3c). Moreover, 1a remained intact, without
any reaction in the absence of thiol, thus indicating
that only a thiyl radical from thiol triggered the
aldehyde (Scheme 3d). To understand disulfide
participation, a crossover experiment between 1a and
2g was conducted in the presence of n-butyl disulfide
under standard reaction conditions. Subsequently,
crossover products were carried out. This result
demonstrates that disulfide may also participate in
this transformation (Scheme 3e). In an open-air
atmosphere, 7 was obtained in 49% yield, whereas in
an O2 atmosphere, 7 did not form. These results
implied that a nitrogen atmosphere is essential for
this transformation (Schemes 3f and 3g). These
reaction mechanisms were studied further through
EPR experiments (see SI).
with the excited organophotocatalyst II and
undergoes a single-electron oxidation process to form
species IV. The generated thiyl radical IVa reacts
with 1 to form an intermediate V. Thiol 2 further
reacts with V, which delivers a thiyl radical and Va.
Va subsequently affords Vb after the elimination of
its water molecule. The thiyl radical then reacts with
Vb to afford VI. VI then favors a single-electron
reduction
process
from
the
reduced
organophotocatalyst III, leading to the formation of
the dithioacetal product 3 (Scheme 4).
Scheme 4. Plausible mechanism
Conclusion
In summary, a mild and efficient protocol for
thioacetalization of aldehydes using a visible-light–
promoted metal-free photoredox catalyst under
solvent-free conditions has been developed. A wide
range
of
aldehydes
containing
aromatic,
heteroaromatic, and α,β-unsaturated aromatic rings
are all well tolerated under the reaction conditions
employed. The protocol provides the expedient
synthesis of cyclic dithioacetal derivatives with five-
or six-membered rings. The reaction is amenable to a
10-g scale synthesis. The control experimental studies
validated the insight of the reaction mechanism. The
eminent features of the present protocol include the
simple and convenient operation, ecofriendliness, low
catalyst loading, high functional group tolerance, ease
of scalability, and practicality.
Experimental Section
General information:
Scheme 3. Control experiments
Merck silica gel 60 (230–400 mesh) were used to purify
the compounds by column chromatography. All
commercial chemicals were used as such. GC-MS analyses
were undertaken on Agilent Technologies 5977A GC
equipped with Agilent 7890B MS. Varian Unity Inova-600
or a Varian Mercury-400 NMR instrument were used to
On the basis of recent literature[16b,21] and the
results of the aforementioned control experiments, we
propose
a
plausible mechanism for this
transformation as follows: Thiol 2 initially interacts
4
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10.1002/adsc.201800999
Advanced Synthesis & Catalysis
record NMR by using CDCl3 solvent, and multiplicity
were determined as singlet s, doublet d, triplet t, double of
doublet dd, multiplet m and broad brs. Chemical shifts and
coupling constant values are determined in parts per
million (ppm) and in hertz (Hz). High-resolution mass
spectra (HRMS) were analyzed on a Jeol JMS-HX 110
spectrometer by the services provided at the National
Chung Hsing University.
29.43, 29.31, 29.11, 28.99, 28.78, 22.63, 14.06. HRMS
(EI) calcd for C31H55BrS2 [M]+ 570.2929, found 570.2938.
2-Chlorobenzaldehyde didodecyldithioacetal (3d):
Following
the
general
procedure,
using
2-
chlorobenzaldehyde (0.140. g, 1.0 mmol), 1-dodecanethiol
(0.445g, 2.2 mmol), eosin Y (0.6 mg, 0.1 mol%), then
purified by column chromatography (SiO2, 10% ethyl
acetate in hexanes) to provide 3d as the colorless oil (0.426
1
General procedure for the synthesis of dithioacetals:
g, 81% yield). H NMR (400 MHz, CDCl3): δ 7.75 (d, J =
8.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.25 (t, J = 8.0 Hz,
1H), 7.15 (t, J = 8.0 Hz, 1H), 5.43 (s, 1H), 2.64 – 2.47 (m,
4H), 1.60 – 1.53 (m, 4H), 1.25 (brs, 36H), 0.88 (t, J = 8.0
Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 138.27, 132.44,
129.52, 129.15, 128.53, 127.10, 48.42, 32.29, 31.87, 29.62,
29.60, 29.55, 29.44, 29.32, 29.11, 28.74, 22.64, 14.07.
HRMS (EI) calcd for C31H55ClS2 [M]+ 526.3434, found
526.3440.
Aldehyde 1, thiol 2 and eosin Y (0.1 mol%) were added to
the Schlenk tube containing a Teflon-coated magnetic stir
bar and was purged by evacuating the tube and back filled
with nitrogen. The reaction mixture was kept for stirring
under 10 W blue LEDs irradiation at room temperature for
12 hours. After completion of the reaction, the crude
reaction mixture was purified by silicagel column
chromatography to afford the pure dithioacetal product.
3-Chlorobenzaldehyde
Following the general
didodecyldithioacetal
procedure, using
(3e):
Benzaldehyde didodecyldithioacetal (3a):[9] Following
the general procedure, using benzaldehyde (0.106g, 1.0
mmol), 1-dodecanethiol (0.445g, 2.2 mmol), eosin Y (0.6
mg, 0.1 mol%), then purified by column chromatography
(SiO2, 10% ethyl acetate in hexanes) to provide 3a as the
yellow oil (0.485 g, 99% yield). 1H NMR (400 MHz,
CDCl3): δ 7.43 (d, J = 8.0 Hz, 2H), 7.31 (t, J = 8.0 Hz, 2H),
7.24 (t, J = 8.0 Hz, 1H), 4.87 (s, 1H), 2.60 – 2.46 (m, 4H),
1.57 – 1.50 (m, 4H), 1.24 (brs, 36H), 0.88 (t, J = 8.0 Hz,
6H). 13C NMR (100 MHz, CDCl3): δ 140.55, 128.37,
127.63, 127.59, 53.07, 32.16, 31.88, 29.63, 29.61, 29.56,
29.46, 29.33, 29.15, 29.08, 28.83, 22.66, 14.10. The above
similar reaction procedure was followed for 10-gram scale
reaction, providing 99.8% yield.
3-
chlorobenzaldehyde (0.140 g, 1.0 mmol), 1-dodecanethiol
(0.445g, 2.2 mmol), eosin Y (0.6 mg, 0.1 mol%), then
purified by column chromatography (SiO2, 10% ethyl
acetate in hexanes) to provide 3e white oil (0.427 g, 81%
yield). 1H NMR (400 MHz, CDCl3): δ 7.44 (s, 1H), 7.32 (d,
J = 8.0 Hz, 1H), 7.24 – 7.21 (m, 2H), 4.81 (s, 1H), 2.60 –
2.46 (m, 4H), 1.55 – 1.52 (m, 4H), 1.25 (brs, 36H), 0.88 (t,
J = 8.0 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 142.77,
134.18, 129.52, 127.74, 125.79, 52.53, 32.15, 31.87, 29.60,
29.55, 29.45, 29.32, 29.13, 29.01, 28.78, 22.64, 14.06.
HRMS (EI) calcd for C31H55ClS2 [M]+ 526.3434, found
526.3426.
2-Methoxybenzaldehyde didodecyldithioacetal (3f):
Following the general procedure, using o-anisaldehyde
(0.136 g, 1.0 mmol), 1-dodecanethiol (0.445g, 2.2 mmol),
eosin Y (0.6 mg, 0.1 mol%), then purified by column
chromatography (SiO2, 10% ethyl acetate in hexanes) to
2-Bromobenzaldehyde
Following the general
didodecyldithioacetal
procedure, using
(3b):
2-
bromobenzaldehyde (0.185g, 1.0 mmol), 1-dodecanethiol
(0.445g, 2.2 mmol), eosin Y (0.6 mg, 0.1 mol%), then
purified by column chromatography (SiO2, 10% ethyl
acetate in hexanes) to provide 3b as the colorless oil (0.485
1
provide 3f as the colorless oil (0.502 g, 96% yield). H
NMR (400 MHz, CDCl3): δ 7.60 (dd, J = 8.0, 4.0 Hz, 1H),
7.18 (t, J = 8.0, 1H), 6.93 (t, J = 8.0 Hz, 1H), 6.82 (d, J =
8.0 Hz, 1H), 5.46 (s, 1H), 3.81 (s, 3H), 2.62 – 2.45 (m, 4H),
1.58 – 1.51 (m, 4H), 1.25 (brs, 36H), 0.88 (t, J = 8.0 Hz,
6H). 13C NMR (100 MHz, CDCl3): δ 155.47, 128.82,
128.44, 128.28, 120.58, 110.21, 55.34, 44.87, 31.95, 31.80,
29.56, 29.54, 29.50, 29.40, 29.25, 29.10, 29.05, 28.75,
22.56, 13.98. HRMS (EI) calcd for C32H58OS2 [M]+
522.3929, found 522.3923.
1
g, 85% yield). H NMR (400 MHz, CDCl3): δ 7.76 (d, J =
8.0 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.28 (t, J = 8.0 Hz,
1H), 7.06 (t, J = 8.0 Hz, 1H), 5.41 (s, 1H), 2.64 – 2.46 (m,
4H), 1.61 – 1.53 (m, 4H), 1.25 (brs, 36H), 0.88 (t, J = 8.0
Hz, 6H). 13C NMR (100 MHz, CDCl3) δ 139.87, 132.36,
129.74, 128.79, 127.67, 123.20, 51.26, 32.28, 31.85, 29.61,
29.59, 29.54, 29.43, 29.31, 29.13, 29.10, 28.70, 22.62,
14.05. HRMS (EI) calcd for C31H55BrS2 [M]+ 570.2929,
found 570.2934.
4-Methoxybenzaldehyde didodecyldithioacetal (3g):
Following the general procedure, using p-anisaldehyde
(0.136 g, 1.0 mmol), 1-dodecanethiol (0.445g, 2.2 mmol),
eosin Y (0.6 mg, 0.1 mol%), then purified by column
chromatography (SiO2, 10% ethyl acetate in hexanes) to
provide 3g white solid (0.502 g, 96% yield). m.p. 39-41°C;
1H NMR (400 MHz, CDCl3): δ 7.35 (d, J = 12.0 Hz, 2H),
6.83 (d, J = 8.0 Hz, 2H), 4.85 (s, 1H), 3.76 (s, 3H), 2.59 –
2.44 (m, 4H), 1.57 – 1.50 (m, 4H), 1.25 (brs, 36H), 0.88 (t,
J = 8.0 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 158.88,
132.46, 128.67, 113.57, 54.99, 52.45, 32.07, 31.83, 29.58,
29.57, 29.52, 29.42, 29.28, 29.11, 29.06, 28.79, 22.60,
4-Bromobenzaldehyde
Following the general
didodecyldithioacetal
procedure, using
(3c):
4-
bromobenzaldehyde (0.185g, 1.0 mmol), 1-dodecanethiol
(0.445g, 2.2 mmol), eosin Y (0.6 mg, 0.1 mol%), then
purified by column chromatography (SiO2, 10% ethyl
acetate in hexanes) to provide 3c yellow oil (0.484 g, 85%
1
yield). H NMR (400 MHz, CDCl3): δ 7.42 (d, J = 8.0 Hz,
2H), 7.31 (d, J = 8.0 Hz, 2H), 4.82 (s, 1H), 2.59 – 2.44 (m,
4H), 1.56 – 1.49 (m, 4H), 1.25 (brs, 36H), 0.88 (t, J = 8.0
Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 139.67, 131.39,
129.26, 121.31, 52.39, 32.07, 31.85, 29.61, 29.59, 29.54,
5
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10.1002/adsc.201800999
Advanced Synthesis & Catalysis
14.02. HRMS (EI) calcd for C32H58OS2 [M]+ 522.3929,
found 522.3931.
HRMS (EI) calcd for C31H55NO2S2 [M]+ 537.3674, found
537.3676.
2-Methylbenzaldehyde didodecyldithioacetal (3h):
Following the general procedure, using o-tolualdehyde
(0.120 g, 1.0 mmol), 1-dodecanethiol (0.445g, 2.2 mmol),
eosin Y (0.6 mg, 0.1 mol%), then purified by column
chromatography (SiO2, 10% ethyl acetate in hexanes) to
3-Nitrobenzaldehyde
Following the general
didodecyldithioacetal
procedure, using
(3l):
3-
nitrobenzaldehyde (0.151 g, 1.0 mmol), 1-dodecanethiol
(0.445g, 2.2 mmol), eosin Y (0.6 mg, 0.1 mol%), then
purified by column chromatography (SiO2, 10% ethyl
acetate in hexanes) to provide 3l yellow oil (0.381 g, 71%
yield). 1H NMR (400 MHz, CDCl3): δ 8.32 (s, 1H), 8.12 (d,
J = 8.0 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.51 (t, J = 8.0
Hz, 1H), 4.95 (s, 1H), 2.64 – 2.48 (m, 4H), 1.58 – 1.52 (m,
4H), 1.25 (brs, 36H), 0.88 (t, J = 8.0 Hz, 6H). 13C NMR
(100 MHz, CDCl3): δ 148.04, 143.15, 133.72, 129.32,
122.56, 52.32, 32.20, 31.82, 29.56, 29.55, 29.49, 29.39,
29.27, 29.06, 28.94, 28.72, 22.59, 14.01. HRMS (EI) calcd
for C31H55NO2S2 [M]+ 537.3674, found 537.3666.
1
provide 3h as the colorless oil (0.502 g, 99% yield). H
NMR (400 MHz, CDCl3): δ 7.65 (d, J = 8.0 Hz, 1H), 7.17
– 7.09 (m, 3H), 5.11 (s, 1H), 2.63 – 2.43 (m, 4H), 2.39 (s,
3H), 1.57 –1.49 (m, 4H), 1.25 (brs, 36H), 0.88 (t, J = 8.0
Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 137.82, 134.86,
130.25, 127.59, 127.25, 126.02, 49.54, 31.86, 29.61, 29.60,
29.55, 29.45, 29.32, 29.13, 29.10, 28.81, 22.62, 19.11,
14.03. HRMS (EI) calcd for C32H58S2 [M]+ 506.3980,
found 506.3975.
3-Methylbenzaldehyde
didodecyldithioacetal
(3i):
4-Nitrobenzaldehyde
Following the general
nitrobenzaldehyde (0.151 g, 1.0 mmol), 1-dodecanethiol
(0.445g, 2.2 mmol), eosin Y (0.6 mg, 0.1 mol%), then
purified by column chromatography (SiO2, 10% ethyl
acetate in hexanes) to provide 3m white solid (0.279 g,
didodecyldithioacetal
procedure, using
(3m):
Following the general procedure, using m-tolualdehyde
(0.120 g, 1.0 mmol), 1-dodecanethiol (0.445g, 2.2 mmol),
eosin Y (0.6 mg, 0.1 mol%), then purified by column
chromatography (SiO2, 10% ethyl acetate in hexanes) to
4-
1
provide 3i as the colorless oil (0.385 g, 76% yield). H
1
NMR (400 MHz, CDCl3): δ 7.24 – 7.15 (m, 3H), 7.04 (d, J
= 8.0 Hz, 1H), 4.83 (s, 1H), 2.60 – 2.46 (m, 4H), 2.33 (s,
3H), 1.57 – 1.50 (m, 4H), 1.25 (brs, 36H), 0.88 (t, J = 8.0
Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 140.42, 137.92,
128.39, 128.12, 124.63, 53.08, 32.13, 31.86, 29.60, 29.59,
29.54, 29.44, 29.31, 29.13, 29.06, 28.80, 22.62, 21.30,
14.04. HRMS (EI) calcd for C32H58S2 [M]+ 506.3980,
found 506.3987.
52% yield). m.p. 44-46°C; H NMR (400 MHz, CDCl3):
1H NMR (400 MHz, CDCl3): δ 8.19 (d, J = 8.0 Hz, 2H),
7.62 (d, J = 12.0 Hz, 2H), 4.91 (s, 1H), 2.63 – 2.47 (m, 4H),
1.59 – 1.51 (m, 4H), 1.25 (brs, 36H), 0.88 (t, J = 8.0 Hz,
6H). 13C NMR (100 MHz, CDCl3): δ 148.23, 147.04,
128.46, 123.62, 52.34, 32.18, 31.82, 29.55, 29.49, 29.39,
29.26, 29.06, 28.94, 28.73, 22.59, 14.01. HRMS (EI) calcd
for C31H55NO2S2 [M]+ 537.3674, found 537.3677.
4-Methylbenzaldehyde
didodecyldithioacetal
(3j):
3-Cyanobenzaldehyde
Following the general
didodecyldithioacetal
procedure, using
(3n):
Following the general procedure, using p-tolualdehyde
(0.120 g, 1.0 mmol), 1-dodecanethiol (0.445g, 2.2 mmol),
eosin Y (0.6 mg, 0.1 mol%), then purified by column
chromatography (SiO2, 10% ethyl acetate in hexanes) to
provide 3j colorless oil (0.446 g, 88% yield). H NMR
(400 MHz, CDCl3): δ 7.31 (d, J = 8.0 Hz, 2H), 7.09 (d, J =
3-
formylbenzonitrile (0.131 g, 1.0 mmol), 1-dodecanethiol
(0.445g, 2.2 mmol), eosin Y (0.6 mg, 0.1 mol%), then
purified by column chromatography (SiO2, 10% ethyl
acetate in hexanes) to provide 3n colorless oil (0.378g,
1
1
73% yield). H NMR (400 MHz, CDCl3): δ 7.75 (s, 1H),
8.0 Hz, 2H), 4.84 (s, 1H), 2.59 – 2.45 (m, 4H), 2.31 (s, 3H), 7.71 (d, J = 8.0 Hz, 1H), 7.55 (d, J = 4.0 Hz, 1H), 7.43 (t, J
1.57 – 1.50 (m, 4H), 1.25 (brs, 36H), 0.88 (t, J = 8.0 Hz,
6H). 13C NMR (100 MHz, CDCl3): δ 137.48, 137.13,
128.94, 127.42, 52.79, 32.05, 31.85, 29.60, 29.59, 29.54,
29.43, 29.30, 29.12, 29.05, 28.79, 22.62, 20.99, 14.03.
HRMS (EI) calcd for C32H58S2 [M]+ 506.3980, found
506.3982.
= 8.0 Hz, 1H), 4.87 (s, 1H), 2.62 – 2.46 (m, 4H), 1.58 –
1.51 (m, 4H), 1.25 (brs, 36H), 0.88 (t, J = 8.0 Hz, 6H). 13C
NMR (100 MHz, CDCl3): δ 142.43, 132.05, 131.12,
129.15, 118.31, 112.39, 52.18, 32.11, 31.77, 29.52, 29.50,
29.45, 29.34, 29.22, 29.02, 28.88, 28.68, 22.55, 13.99.
HRMS (EI) calcd for C32H55NS2 [M]+ 517.3776, found
517.3783.
2-Nitrobenzaldehyde
Following the general
didodecyldithioacetal
procedure, using
(3k):
2-
2-Hydroxybenzaldehyde didodecyldithioacetal (3o):
Following the general procedure, using salicylaldehyde
(0.122 g, 1.0 mmol), 1-dodecanethiol (0.445g, 2.2 mmol),
eosin Y (0.6 mg, 0.1 mol%), then purified by column
nitrobenzaldehyde (0.151 g, 1.0 mmol), 1-dodecanethiol
(0.445g, 2.2 mmol), eosin Y (0.6 mg, 0.1 mol%), then
purified by column chromatography (SiO2, 10% ethyl
acetate in hexanes) to provide 3k as the yellow oil (0.419 g, chromatography (SiO2, 10% ethyl acetate in hexanes) to
1
78% yield). 1H NMR (400 MHz, CDCl3): δ 7.99 (d, J = 8.0
Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.59 (t, J = 8.0 Hz, 1H),
7.37 (t, J = 8.0 Hz, 1H), 5.72 (s, 1H), 2.66 – 2.51 (m, 4H),
1.54 (d, J = 8.0 Hz, 4H), 1.25 (brs, 36H), 0.88 (t, J = 8.0
Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 147.90, 135.99,
132.92, 130.42, 128.10, 124.06, 46.67, 32.67, 31.83, 29.56,
29.50, 29.39, 29.28, 29.04, 28.97, 28.68, 22.60, 14.02.
provide 3o as the colorless oil (0.504g, 99% yield). H
NMR (400 MHz, CDCl3): δ 7.20 – 7.17 (m, 2H), 7.04 (s,
1H), 6.89 – 6.83 (m, 2H), 5.08 (s, 1H), 2.60 – 2.48 (m, 4H),
1.59 – 1.51 (m, 4H), 1.24 (brs, 36H), 0.88 (t, J = 8.0 Hz,
6H). 13C NMR (100 MHz, CDCl3): δ 154.62, 129.32,
129.21, 123.65, 120.07, 117.33, 109.81, 49.58, 32.22,
31.81, 29.55, 29.49, 29.37, 29.26, 29.02, 28.92, 28.66,
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800999
Advanced Synthesis & Catalysis
22.58, 13.99. HRMS (EI) calcd for C31H56OS2 [M]+
508.3773, found 508.3769.
1-Naphthaldehyde didodecyldithioacetal (3t): Following
the general procedure, using 1-Naphthaldehyde (0.156 g,
1.0 mmol), 1-dodecanethiol (0.445g, 2.2 mmol), eosin Y
(0.6 mg, 0.1 mol%), then purified by column
chromatography (SiO2, 10% ethyl acetate in hexanes) to
3,5-Dimethoxybenzaldehyde didodecyldithioacetal (3p):
Following
the
general
procedure,
using
3,5-
1
provide 3t as the colorless oil (0.537g, 99% yield). H
dimethoxybenzaldehyde (0.166 g, 1.0 mmol), 1-
dodecanethiol (0.445g, 2.2 mmol), eosin Y (0.6 mg, 0.1
mol%), then purified by column chromatography (SiO2,
10% ethyl acetate in hexanes) to provide 3p colorless oil
NMR (400 MHz, CDCl3): δ 8.24 (bs, 1H), 7.80 – 7.69 (m,
3H), 7.49 (t, J = 8.0 Hz, 1H), 7.43 – 7.36 (m, 2H), 5.67 (bs,
1H), 2.66 – 2.47 (m, 4H), 1.57 – 1.49 (m, 4H), 1.25 (brs,
36H), 0.87 (t, J = 8.0 Hz, 6H). 13C NMR (100 MHz,
CDCl3): δ 135.15, 133.93, 130.39, 128.78, 128.33, 125.87,
125.69, 125.49, 124.90, 123.16, 32.34, 31.86, 29.60, 29.59,
29.53, 29.42, 29.31, 29.11, 29.02, 28.80, 22.63, 14.05.
HRMS (EI) calcd for C35H58S2 [M]+ 542.3980, found
542.3981.
1
(0.525g, 95% yield). H NMR (400 MHz, CDCl3): δ 6.61
(d, J = 4.0 Hz, 2H), 6.34 (s, 1H), 4.78 (s, 1H), 3.76 (s, 6H),
2.61 – 2.48 (m, 4H), 1.58 – 1.51 (m, 4H), 1.25 (brs, 36H),
0.88 (t, J = 8.0 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ
160.55, 142.83, 105.46, 99.63, 55.07, 53.26, 32.22, 31.81,
29.56, 29.54, 29.50, 29.41, 29.26, 29.10, 29.02, 28.76,
22.57, 13.99. HRMS (EI) calcd for C33H60O2S2 [M]+
552.4035, found 552.4033.
Cinnamaldehyde
didodecyldithioacetal
(3u):[22a]
Following the general procedure, using cinnamaldehyde
(0.132g, 1.0 mmol), 1-dodecanethiol (0.445g, 2.2 mmol),
eosin Y (0.6 mg, 0.1 mol%), then purified by column
chromatography (SiO2, 10% ethyl acetate in hexanes) to
3,5-Dichloro-2-hydroxybenzaldehyde
didodecyldithioacetal (3q): Following the general
procedure, using 3,5-Dichlorobenzaldehyde (0.175 g, 1.0
mmol), 1-dodecanethiol (0.445g, 2.2 mmol), eosin Y (0.6
mg, 0.1 mol%), then purified by column chromatography
(SiO2, 10% ethyl acetate in hexanes) to provide 3q as the
1
provide 3u as the yellow oil (0.367g, 71% yield). H NMR
(400 MHz, CDCl3): δ 7.37 (d, J = 8.0 Hz, 2H), 7.29 (t, J =
8.0 Hz, 2H), 7.21 (t, J = 8.0 Hz, 1H), 6.51 (d, J = 16.0 Hz,
1H), 6.19 – 6.06 (m, 1H), 4.47 (d, J = 8.0 Hz, 1H), 2.67 –
2.56 (m, 4H), 1.63 – 1.56 (m, 4H), 1.25 (brs, 36H), 0.88 (t,
J = 8.0 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 136.03,
130.55, 128.41, 128.04, 127.65, 127.56, 126.39, 51.25,
31.84, 31.10, 29.57, 29.53, 29.44, 29.33, 29.29, 29.15,
28.84, 22.61, 14.04. HRMS (EI) calcd for C33H58S2 [M]+
518.3980, found 518.3989.
1
colorless oil (0.428g, 74% yield). H NMR (400 MHz,
CDCl3): δ 7.40 (d, J = 4.0 Hz, 1H), 7.26 (d, J = 4.0 Hz,
1H), 6.36 (s, 1H), 5.21 (s, 1H), 2.64 – 2.49 (m, 4H), 1.61 –
1.53 (m, 4H), 1.25 (brs, 36H), 0.88 (t, J = 8.0 Hz, 6H). 13
C
NMR (100 MHz, CDCl3): δ 147.50, 128.84, 127.93,
127.60, 125.30, 121.08, 46.71, 39.03, 31.85, 29.58, 29.53,
29.42, 29.30, 22.61, 14.03. HRMS (EI) calcd for
C31H54Cl2OS2 [M]+ 576.2993, found 576.2995.
Benzaldehyde
dicyclohexyldithioacetal
(4a):[22b]
Following the general procedure, using benzaldehyde
(0.106g, 1.0 mmol), cyclohexanethiol (0.256 g, 2.2 mmol),
eosin Y (0.6 mg, 0.1 mol%), then purified by column
chromatography (SiO2, 10% ethyl acetate in hexanes) to
provide 4a as the yellow oil (0.318 g, 99% yield). 1H NMR
(400 MHz, CDCl3): δ 7.45 (d, J = 8.0 Hz, 2H), 7.28 (t, J =
8.0 Hz, 2H), 7.20 (t, J = 8.0 Hz, 1H), 5.00 (s, 1H), 2.76 –
2.69 (m, 2H), 1.93 – 1.86 (m, 4H), 1.73 – 1.69 (m, 4H),
1.55 (s, 2H), 1.36 – 1.24 (m, 10H). 13C NMR (100 MHz,
CDCl3): δ 141.06, 128.14, 127.41, 127.30, 126.81, 49.52,
43.88, 33.06, 25.56. HRMS (EI) calcd for C19H28S2 [M]+
320.1632, found 320.1629.
2-Furaldehyde didodecyldithioacetal (3r): Following the
general procedure, using furfural (0.096 g, 1.0 mmol), 1-
dodecanethiol (0.445g, 2.2 mmol), eosin Y (0.6 mg, 0.1
mol%), then purified by column chromatography (SiO2,
10% ethyl acetate in hexanes) to provide 3r as the
1
colorless oil (0.371g, 77% yield). H NMR (400 MHz,
CDCl3): δ 7.34 (s, 1H), 6.32 – 6.28 (m, 2H), 4.98 (s, 1H),
2.68 – 2.51 (m, 4H), 1.56 – 1.50 (m, 4H), 1.26 (brs, 36H),
0.88 (t, J = 8.0 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ
152.27, 141.82, 110.14, 107.37, 45.80, 31.81, 31.24, 29.56,
29.54, 29.50, 29.40, 29.26, 29.09, 29.01, 28.80, 22.58,
13.99. HRMS (EI) calcd for C29H54OS2 [M]+ 482.3616,
found 482.3617.
2-Methylbenzaldehyde dicyclohexyldithioacetal (4b):
Following the general procedure, using o-tolualdehyde
(0.120 g, 1.0 mmol), cyclohexanethiol (0.256 g, 2.2 mmol),
eosin Y (0.6 mg, 0.1 mol%), then purified by column
chromatography (SiO2, 10% ethyl acetate in hexanes) to
2-Thiophenecarboxaldehyde didodecyldithioacetal (3s):
Following
the
general
procedure,
using
2-
Thiophenecarboxaldehyde (0.112 g, 1.0 mmol), 1-
dodecanethiol (0.445g, 2.2 mmol), eosin Y (0.6 mg, 0.1
mol%), then purified by column chromatography (SiO2,
10% ethyl acetate in hexanes) to provide 3s as the colorless
1
provide 4b as the colorless oil (0.331 g, 99% yield). H
NMR (400 MHz, CDCl3): δ 7.76 (d, J = 8.0 Hz, 1H), 7.19
– 7.08 (m, 3H), 5.24 (s, 1H), 2.77 (t, J = 8.0 Hz, 2H), 2.41
(s, 3H), 1.94 – 1.84 (m, 4H), 1.70 (s, 4H), 1.55 (s, 2H),
1.36 – 1.24 (m, 10H). 13C NMR (100 MHz, CDCl3): δ
138.37, 134.51, 130.09, 127.93, 127.16, 126.13, 46.11,
43.93, 33.26, 33.17, 25.64, 19.03. HRMS (EI) calcd for
C20H30S2 [M]+ 334.1789, found 334.1791.
1
oil (0.489g, 98% yield). H NMR (400 MHz, CDCl3): δ
7.18 (d, J = 4.0, 1H), 7.06 (s, 1H), 6.88 – 6.86 (m, 1H),
5.17 (s, 1H), 2.69 – 2.52 (m, 4H), 1.60 – 1.53 (m, 4H),
1.25 (brs, 36H), 0.88 (t, J = 8.0 Hz, 6H). 13C NMR (100
MHz, CDCl3): δ 145.12, 126.10, 125.43, 125.05, 48.30,
31.83, 29.58, 29.56, 29.52, 29.42, 29.28, 29.11, 28.94,
28.83, 22.60, 14.02. HRMS (EI) calcd for C29H54S3 [M]+
498.3388, found 498.3379.
4-Methoxylbenzaldehyde dicyclohexyldithioacetal (4c):
Following the general procedure, using p-anisaldehyde
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800999
Advanced Synthesis & Catalysis
(0.136 g, 1.0 mmol), cyclohexanethiol (0.256 g, 2.2 mmol), mol%), then purified by column chromatography (SiO2,
eosin Y (0.6 mg, 0.1 mol%), then purified by column
chromatography (SiO2, 10% ethyl acetate in hexanes) to
provide 4c as the colorless oil (0.347 g, 99% yield). H
NMR (400 MHz, CDCl3): δ 7.38 (d, J = 8.0 Hz, 2H), 6.82
(d, J = 8.0 Hz, 2H), 4.99 (s, 1H), 3.76 (s, 3H), 2.71 (s, 2H),
1.89 (s, 4H), 1.70 (s, 4H), 1.54 (s, 2H), 1.41 – 1.23 (m,
10H). 13C NMR (100 MHz, CDCl3): δ 158.67, 132.99,
128.55, 113.50, 54.95, 48.89, 43.84, 33.08, 25.60. HRMS
(EI) calcd for C20H30OS2 [M]+ 350.1738, found 350.1740.
10% ethyl acetate in hexanes) to provide 5c white solid
(0.124 g, 59% yield). m.p. 80-82 °C; H NMR (400 MHz,
1
1
CDCl3): δ 7.59 (d, J = 8.0 Hz, 1H), 7.23 – 7.14 (m, 3H),
5.32 (s, 1H), 3.13 – 3.06 (m, 2H), 2.95 – 2.90 (m, 2H),
2.45 (s, 3H), 2.22 – 2.15 (m, 1H), 2.00 – 1.89 (m, 1H). 13C
NMR (100 MHz, CDCl3): δ 137.06, 134.92, 130.33,
128.06, 127.73, 126.51, 48.16, 32.29, 25.16, 18.99.
(E)-2-Styryl-1,3-dithiolane (5d):[22d] Following the
general procedure, using cinnamaldehyde (0.132g, 1.0
mmol), 1,2-ethanedithiol (0.103g, 1.1 mmol), eosin Y (0.6
mg, 0.1 mol%), then purified by column chromatography
(SiO2, 10% ethyl acetate in hexanes) to provide 5d as the
yellow oil (0.073g, 35% yield). 1H NMR (400 MHz,
CDCl3): δ 7.38 – 7.36 (m, 2H), 7.32 – 7.28 (m, 2H), 7.26 –
7.21 (m, 1H), 6.51 (d, J = 16.0 Hz, 1H), 6.21 (dd, J = 16.0,
8.0 Hz, 1H), 5.23 (d, J = 8.0 Hz, 1H), 3.41 – 3.25 (m, 4H).
13C NMR (100 MHz, CDCl3): δ 135.98, 130.05, 128.96,
128.44, 127.72, 126.52, 54.40, 39.52.
(Phenylmethylene)bis(sec-butylsulfane)
(4d):[9]
Following the general procedure, using benzaldehyde
(0.106g, 1.0 mmol), 2-butanethiol (0.198 g, 2.2 mmol),
eosin Y (0.6 mg, 0.1 mol%), then purified by column
chromatography (SiO2, 10% ethyl acetate in hexanes) to
1
provide 4d as the colorless oil (0.266 g, 99% yield). H
NMR (400 MHz, CDCl3): δ 7.47 (d, J = 4.0 Hz, 2H), 7.29
(t, J = 8.0 Hz, 2H), 7.22 (t, J = 8.0 Hz, 1H), 4.94 (s, 1H),
2.86 – 2.64 (m, 2H), 1.58 – 1.46 (m, 4H), 1.21 (t, J = 8.0
Hz, 6H), 0.95 – 0.88 (m, 6H). 13C NMR (100 MHz,
CDCl3): δ 140.98, 128.27, 127.63, 127.48, 50.50, 42.30,
29.37, 20.51, 11.02. HRMS (EI) calcd for C15H24S2 [M]+
268.1319, found 268.1323.
Acknowledgements
This work was financially supported by the Ministry of
Science and Technology, Taiwan (Most 107-2113-M-005-
019-MY3), National Chung Hsing University, Research
Center for Sustainable Energy and Nanotechnology
(RCSEN), and the "Innovation and Development Center of
Sustainable Agriculture (IDCSA)" from The Featured
Areas Research Center Program within the framework of
the Higher Education Sprout Project by the Ministry of
Education (MOE) in Taiwan.
4-Anisaldehyde diphenyldithioacetal (4e):[14] Following
the general procedure, using p-anisaldehyde (0.136 g, 1.0
mmol), thiophenol (0.242 g, 2.2 mmol), eosin Y (0.6 mg,
0.1 mol%), then purified by column chromatography (SiO2,
10% ethyl acetate in hexanes) to provide 4e as the
1
colorless oil (0.101 g, 30% yield). H NMR (400 MHz,
CDCl3): δ 7.35 – 7.21 (m, 12H), 6.79 (d, J = 8.0 Hz, 2H),
5.42 (s, 1H), 3.76 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
159.21, 134.68, 132.31, 131.59, 129.04, 128.75, 127.61,
113.77, 59.68, 55.22.
References
2-(o-Tolyl)-1,3-dithiolane (5a):[22c] Following the general
procedure, using o-tolualdehyde (0.120g, 1.0 mmol), 1,2-
ethanedithiol (0.103g, 1.1 mmol), eosin Y (0.6 mg, 0.1
mol%), then purified by column chromatography (SiO2,
10% ethyl acetate in hexanes) to provide 5a as the yellow
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oil ( 0.159g, 81% yield). H NMR (400 MHz, CDCl3): δ
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3.54 – 3.32 (m, 4H), 2.43 (s, 3H). 13C NMR (100 MHz,
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1H), 3.10 – 3.03 (m, 2H), 2.93 – 2.88 (m, 2H), 2.20 – 2.14
(m, 1H), 1.99 – 1.88 (m, 1H). 13C NMR (100 MHz,
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procedure, using o-tolualdehyde (0.120g, 1.0 mmol), 1,3-
propanedithiol (0.119g, 1.1 mmol), eosin Y (0.6 mg, 0.1
[5] a) F. Althoff, K. Benzing, P. Comba, C.
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This article is protected by copyright. All rights reserved.

10.1002/adsc.201800999
Advanced Synthesis & Catalysis
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Visible-Light Photoredox-Catalyzed
Thioacetalization of Aldehydes Under Metal-Free
and Solvent-Free Conditions
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Kai Du, Shao-Chien Wang, R. Sidick Basha, and
Chin-Fa Lee*
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