Photoreduction of aliphatic and aromatic thioketals: New access to the reduction of carbonyl groups by a desulfurization chain process

Article abstract of DOI:10.1016/j.tetlet.2012.12.118

Aromatic and aliphatic ketones can be converted to methylene groups by desulfurization of the corresponding dithioketals in moderate to good yields. The reaction proceeds by photoinduced electron transfer from tert-BuOK in the presence of 1,4-dicyclohexadiene as hydrogen atom donor. The diene is able to trigger and keep a chain process by hydrogen transfer-proton transfer reactions.

Full text of DOI:10.1016/j.tetlet.2012.12.118

Tetrahedron Letters 54 (2013) 1515–1518
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Photoreduction of aliphatic and aromatic thioketals: new access to the
reduction of carbonyl groups by a desulfurization chain process
⇑
⇑
Gabriela Oksdath-Mansilla, Juan E. Argüello , Alicia B. Peñéñory
INFIQC, Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina
a r t i c l e i n f o
a b s t r a c t
Article history:
Aromatic and aliphatic ketones can be converted to methylene groups by desulfurization of the corre-
sponding dithioketals in moderate to good yields. The reaction proceeds by photoinduced electron trans-
fer from tert-BuOK in the presence of 1,4-dicyclohexadiene as hydrogen atom donor. The diene is able to
trigger and keep a chain process by hydrogen transfer–proton transfer reactions.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 10 December 2012
Revised 20 December 2012
Accepted 28 December 2012
Available online 12 January 2013
Keywords:
Carbonyl reduction
Thioketals
Photochemistry
Electron transfer
Radical anion
Introduction
These results encouraged us to develop a novel photoinduced
reductive process for an aromatic and aliphatic ketone to methy-
Carbonyl reduction is a very well described and useful reaction
in organic chemistry.1 A carbonyl group can be reduced to the alco-
hol, or the oxygen atom can be removed altogether in a process
called deoxygenation. The methodologies most commonly applied
to reduce a ketone carbonyl group to a methylene include Clem-
mensen and Wolff–Kishner reductions,2 the former being more
extensively employed (zinc amalgam and concentrated HCl). How-
ever, the substrate must be stable in the strongly acidic conditions.
Acid sensitive substrates should be reduced by the latter method-
ology, which requires treatment of aldehyde and ketone hydra-
zones with strong base (NH2–NH2/KOH, 200 °C). A further, milder
method is the Mozingo reduction.2 In this reaction a thioketal is
first produced by the reaction of the ketone with an appropriate
thiol. The product is then hydrogenolyzed to the alkane, using
Raney Nickel.
Recently we have reported a comprehensive study of the reac-
tions of 2-aryl-1,3-dithiane anion (1) with neopentyl and neophyl
iodides (2), under a variety of conditions in DMSO at 20 °C. The
substitution proceeds by a SRN1 mechanism with radicals and rad-
ical anions as intermediates. This mechanism was suggested
mainly from observation of the products from the C–S bond
fragmentation of the radical anion of the substitution product
(products 5 and 6 in (Eq. 1)).3
lene transformation by desulfurization of the corresponding
dithioketals. This protocol represents an environmentally friendly
alternative that avoids the use of transition metals and toxic/explo-
sive reagents such as mercury, hydrazine, and molecular hydrogen.
R
R
R
S
S
S
S
hν
2
+
I
+
S
S
Ph
Ph
DMSO
4
3
1
R
R
R
+
+
Ph
Ph
5
6
2, R = Me, Ph
ð1Þ
In this Letter, the reduction of a family of 1,3-dithianes and
1,3-dithiolanes in the presence of tert-BuOK/1,4-cyclohexadiene
under photostimulation is reported (Scheme 1). The synthetic
outcome as well as a detailed mechanistic exploration is discussed
on the basis of quantitative photochemical measurements.
t-BuOK, hν
O
SH SH
R2
R1
R2
S
S
R1
R2
R1
R1= C6H5, p-OMe-C6H4, p-CN-C6H4, 1-C10H7
R2= C6H5, p-OMe-C6H4, C6H5CH2, Me
⇑
Corresponding authors. Tel.: +54 351 4334170; fax: +54 351 4333030.
E-mail addresses: jea@fcq.unc.edu.ar (J.E. Argüello), penenory@fcq.unc.edu.ar
(A.B. Peñéñory).
Scheme 1.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.12.118

1516
G. Oksdath-Mansilla et al. / Tetrahedron Letters 54 (2013) 1515–1518
Results and discussion
This reaction proceeded with the formation of a CTC between 7
and tert-BuOK prior to the ET, as confirmed by UV–vis absorption
spectroscopy. Neither dithiane 7 nor tert-BuOK shows absorption
to red at 350 nm. However, when increasing the amount of the
base relative to 7, a new absorption band at a maximum of
467 nm is observed (Fig. 1). Therefore, this new absorption band
can be ascribed to an interaction between 7 and the tert-BuOK, that
is, the formation of a CTC between both species.6
In the absence of 1,4-cyclohexadiene, upon photoinduced elec-
tron transfer (PET), the radical anion of dithiane 7 is formed, frag-
mentation of the C–S bond yields distonic radical anion 12 that
gives intermediate 13 after hydrogen abstraction (Eqs. (4)–(7)).
The mediation of 13 was confirmed by the presence of its methyl-
ated derivative 11 found at a shorter irradiation time ((Eq. 3) and
Scheme 2). Further reduction of 13 generates diphenylmethane
(8) and methylated 1,3-propyldisulfide when quenched by methyl
iodide (Scheme 2).
Photoinduced reductive process of dithioketals
We began exploring the photoinduced ET reduction of dithiane
derivatives as an alternative for the de-oxygenation of carbonyl
groups. 2,2-Diphenyl-1,3-dithiane (7) was selected as a model
compound for optimization of the reductive conditions.4 Although
different electron donors, such as cyclohexanone enolate anion,
2-naphthoxide ion, tert-BuOK, DABCO, N,N-dimethylaniline, and
N,N,N0,N0-tetramethyl-benzene-1,4-diamine were evaluated in
DMSO under a nitrogen atmosphere and irradiation at kmax
>350 nm, only tert-BuOK was effective. Thus, the photoinduced
reduction of 7 with 3 equiv of this base gave diphenylmethane
(8) in 72% yield together with 1,1,2,2-tetraphenylethane (9) and
1,1,2,2-tetraphenylethene (10) in 17% and 11% yields, respectively
(Table 1, entry 1) (Eq. 2).
t-BuOK, hν IMe
Ph
Ph
Ph
Ph
S
S
t-BuOK
Ph
SMe
Ph
+
(CTC)
DMSO
S
S
ð4Þ
Ph Ph
Ph Ph
MeS
8
9
ð2Þ
7
7
Ph
Ph
+
hν
-
ð5Þ
ð6Þ
Ph
Ph
(CTC)
7
10
When this reductive process was performed in the presence of
3 equiv of a good hydrogen atom donor such as 1,4-cyclohexadi-
ene, the yield of 8 increased up to 92% and only 8% of 9 was
obtained (Table 1, entry 2). The yield of diphenylmethane drops
to 37% in the presence of a good electron acceptor such as p-DNB
(Table 1, entry 3). The dark reaction gave 52% yield of reduction,
and this reaction was also inhibited by p-DNB (Table 1, entries 4
and 5). The acceleration by light together with the inhibition in
the presence of a strong electron acceptor (p-DNB) suggests a pho-
toinduced electron-transfer reaction between the dithiane and the
base. In order to gain more information on the intermediates, the
reaction was quenched by IMe after 2 h irradiation. The product
analysis reveals the presence of 3-(methylthio)propyl diphenyl-
methyl sulfide (11)5 (Eq. 3), which at a longer irradiation time is
further reduced to diphenylmethane (Table 1, entry 6).
-
-
S
Ph
S
S
7
Ph
12
SH
-
S
Ph
S
12
ð7Þ
Ph
13
1,4-Cyclohexadiene improves the selectivity of the reaction by
decreasing the yield of dimer 9; it also seems to accelerate the
overall process. Thus, we gain greater reactivity and more selectiv-
ity by the addition of this particular hydrogen donor. After hydro-
gen donation, a cyclohexadienyl radical is formed; we wondered
whether this intermediate could trigger a chain reaction since it
is well accepted, the key step in the hydrogen atom substitution
reactions (HAS) is the addition of an aryl radical to an arene to af-
ford cyclohexadienyl-type radicals. In basic media, re-aromatiza-
tion of these intermediates can occur by deprotonation to render
the radical anion of the substitution product, which is a strong
1) hν, t-BuOK,
1,4-cyclohexadiene
S
S
Ph
S
S
Me
ð3Þ
+
Ph
Ph
Ph Ph
2) IMe
Ph
7
8
11
Table 1
1.0
Photoinduced reduction of 2,2-diphenyl-1,3-dithiane (7) with tert-BuOK in DMSOa
[tert-BuOK]
Entry
Conditions
Product yields (%)
8
9
10
2,2-diphenyl-1,3-dithiane (7)
1b
h
h
h
m
m
m
/
72
17
8
—
—
—
—
11
—
—
—
—
—
tert-BuOK 0.030 M
tert-BuOK 0.035 M
tert-BuOK 0.040 M
tert-BuOK 0.044 M
tert-BuOK 0.047 M
tert-BuOK 0.049 M
2c
/1,4-cyclohexadiene
/1,4-cyclohexadiene/p-DNB
92
37
52
35
24f
0.5
3c,d
4c
Dark/1,4-cyclohexadiene
Dark/1,4-cyclohexadiene/p-DNB
hm/1,4-cyclohexadiene/IMe
5c,d
6c,e
a
Irradiation at kmax >350 nm for 3 h under nitrogen atmosphere, at room tem-
perature; [7] = 0.1 M; tert-BuOK = 0.3 M. Reaction quenched with IMe. Product yield
determined by CG using the internal method, error <5%.
0.0
b
This reaction was quenched with NH4NO3.
1,4-Cyclohexadiene = 0.3 M.
p-DNB = 0.3 M.
Irradiated for 2 h.
c
400
500
600
d
Wavelength (nm)
e
f
Figure 1. UV–vis spectra of 2,2-diphenyl-1,3-dithiane (7) 1.2 ꢀ 10ꢁ4 M and CTC
formation with increasing concentrations of tert-BuOK.
Together with 30% yield of 3-(methylthio)propyl diphenylmethyl sulfide (11)
(Eq. 3).

G. Oksdath-Mansilla et al. / Tetrahedron Letters 54 (2013) 1515–1518
1517
t-BuOK, hν
IMe
SMe
7
13
7
Ph Ph
t-BuOK
8
-
-
S
S
Ph
S
S
S
IMe
Ph
S
8
Ph
12
13
Ph
MeS
SMe
11
Scheme 2.
Ph Ph
t-BuOK
(C6H6)
Ph
S
S
S
Ph
R
13
t-BuOK
-
7, ET
7
-
t-BuOK, hν or C6H6
RH
t-BuOH
Scheme 4.
Scheme 3.
Table 2
Photochemical reduction of dithianes and dithiolanes with tert-BuOK in DMSO.a
reducing agent, and transfers its odd electron to the substrate.7 For
this reason, the role of the hydrogen donor as a chain reaction ini-
tiator was further explored.
Entry
Dithiane
Product yield (%)
92b
Ph Ph
To measure efficiency and chain length in a photochemical reac-
tion, it is necessary to know the quantum yield for product forma-
tion (UP), and also information on the quantum yield for the
initiation step (Ui). Thus, it is possible to obtain a good approxima-
tion of the propagation efficiency (i.e., chain length, c.l.) from the
ratio of the overall quantum yield and the quantum yield of the ini-
S
S
1
Ph Ph
7
7
S
S
MeO
OMe
2
tiation step (c.l. = UP/
Ui)8 By using our model compound 7, quanti-
MeO
1
4
OMe
tative information was measured by chemical actinometry.9 In the
absence of hydrogen donor and at the concentration indicated in
Table 1, the quantum yield for the reduction of 7 by tert-BuOK is
0.007. The addition of 3 equiv of 1,4-cyclohexadiene enhanced
the quantum yield up to 0.03. This result indicates that the reaction
is faster when 1,4-cyclohexadiene is present. The acceleration in
3c
34
Ph
83
S
S
Ph
NC
Ph
4
15
NC
77e
54
the photoreduction of
7 can be explained considering that
S
Ph
S
5d
5
1,4-cyclohexadiene not only donates a hydrogen atom but also
triggers a chain reaction by deprotonation of cyclohexadienyl rad-
ical by tert-BuOK to render a benzene radical anion, which trans-
fers its odd electron to the dithiane 7, propagating a chain
(Scheme 3). Moreover, if we consider the quantum yield of the
reaction in the absence of hydrogen donor as the initiation quan-
tum yield, an approximate value of four can be obtained for the
chain length when the diene is added.
Once the dithiane radical anion is formed (Eqs. 4 and 5), it
follows the proposed mechanism (Scheme 4). A chain reaction is
included to account for the increase in photonic efficiency in the
presence of 1,4-cyclohexadiene as hydrogen donor.
The observed reactivity of the system tert-BuOK/1,4-cyclohexa-
diene toward 2,2-diphenyl-1,3-dithiane encouraged us to further
explore the potential of this procedure. Quite a few examples of
the use of commercially available ketones are included. The selec-
tion of ketones was based on the inclusion of electron-donating
and electron-withdrawing groups and the use of aliphatic ketones.
Dithioketals were synthesized according to reported procedure.
Thus, using these optimized reaction conditions, we evaluated
the scope of this methodology for the reduction of several dithioke-
tals (Table 2).
16
S
S
6
17
40
S
7f
8f
S
18
44
S
S
19
a
Irradiation at kmax >350 nm for 3 h under nitrogen atmosphere, at room tem-
perature; [dithiane] = 0.1 M; tert-BuOK = 0.3 M; 1,4-cyclohexadiene = 0.3 M. Reac-
tion quenched with NH4NO3. Product yield determined by CG using the internal
method, error <5%.
b
Together with 9 in 8% yield.
In DMF at 70 °C with 4 equiv tert-BuOK (tert-BuOK = 0.4 M).
Irradiation at kmax = 300 nm.
Together with alkene 6 in 23% yield.
c
d
e
f
In DMF at 70 °C with 8 equiv tert-BuOK (tert-BuOK = 0.8 M) for 6 h.
This procedure is compatible with both electron–donor and
electron–acceptor groups on aromatic dithianes. As expected good
yields are obtained for the CN derivative;10 however, for the dithi-
ane bearing OMe substituents, the yield of the reduction product
was moderate requiring a higher temperature (Table 2, entries 1–
3). This is particularly relevant since desulfurization of dithianes by
Raney nickel or Na in liquid ammonia is not possible for ketones
bearing a CN group. Dithiane 16 is stable at 350 nm and its reduc-
tion was efficient at 300 nm affording a good yield of the hydrocar-
bon 5 with a low amount of 6. Finally, this methodology can also be
extended to aliphatic ketones (Table 2, entries 7 and 8). For this
purpose, benzene-1,2-dithiol was employed as a protecting group
and chromophore in dithianes 1811 and 19;12 longer irradiation
time and 8 equiv of tert-BuOK were required to obtain moderate
yields (40–44%).
In conclusion, we have developed photoinduced reductive
methodology to convert the carbonyl group in aromatic and ali-

1518
G. Oksdath-Mansilla et al. / Tetrahedron Letters 54 (2013) 1515–1518
3.0 mmol), dithiane 7 (272.0 mg, 1.0 mmol) and 1,4-cyclohexadiene (284 lL,
phatic ketones to CH2 groups by desulfurization of the correspond-
ing dithioketals. This protocol is an environmentally friendly alter-
native to the current reduction methodologies.
3.0 mmol) were added to the degassed solvent under nitrogen. After irradiation
as indicated in Table 1, the reaction was quenched by the addition of excess
ammonium nitrate and 10 mL of water, and the mixture was extracted with
methylene chloride (3 ꢀ 20 mL). The organic extract was washed twice with
water and dried over anhydrous MgSO4, and the products were quantified by
GC using the internal standard method, or isolated by radial chromatography
from the crude product reaction mixture.
Acknowledgments
5. 3-(Methylthio)propyl diphenylmethyl sulfide (11) liquid. 1H NMR: d = 1.78–1.85
(q, 2H); 2.04 (s, 3H); 2.47–2.55 (m, 4H); 5.15 (s, 1H); 7.20–7.24 (m, 2H); 7.28–
7.32 (m, 4H); 7.41–7.43 (m, 4H). 13C NMR: d = 15.5; 31.2; 33.1; 54.2; 127.2;
128.3; 128.6; 141.4 ppm. MS (EI+), m/z (relative intensity), 167 (62); 165 (50);
152 (25); 121 (100); 73(28). HRMS (MNa+), calcd for C17H20NaS2 311.0899,
found 311.0793.
This work was supported partly by Consejo Nacional de Investi-
gaciones Científicas y Técnicas (CONICET) SECYT-UNC and Fondo
de Ciencia y Tecnología (FONCyT), Argentina. G.O.-M. gratefully ac-
knowledges the receipt of a fellowship from CONICET.
6. Foster, R. Organic Charge–Transfer Complexes; Academic Press: New York, 1969.
7. Studer, A.; Curran, D. P. Angew. Chem., Int. Ed. 2011, 50, 5018–5022.
8. Argüello, J. E.; Peñéñory, A. B.; Rossi, R. A. J. Org. Chem. 2000, 65, 7175–7182.
9. Actinometer potassium ferrioxalate was used at k = 420 nm (a) Hatchard, C. G.;
Parker, C. A. J. Chem. Soc. 1956, 518–536; (b) Murov, S. L.; Carmichael, I.; Hung,
G. L. Handbook of Photochemistry, 2nd ed.; Marcel Decker Inc.: New York, 1993.
10. 4-(2-Benzyl-1,3-dithian-2-yl) benzonitrile (15). Solid mp: 98.3–98.5 °C 1H NMR:
d = 1.94–1.97 (m, 2H); 2.52–2.60 (m, 2H); 2.64–2.70 (m, 2H); 3.25 (s, 2H);
6.70–6.71 (d, J = 7 Hz, 2H); 7.09–7.20 (m, 3H); 7.58–7.60 (d, J = 8.7 Hz, 2H);
7.84–7.86 (d, J = 8.7 Hz, 2H). 13C NMR: d = 24.7; 27.5; 51.3; 59.2; 110.9; 118.8;
127.3; 127.6; 130.4; 130.8; 132.1; 133.5; 146.7 ppm. MS (EI+), m/z (relative
intensity), 220 (100); 204 (8); 190 (5); 146 (54); 91 (14). HRMS (MH+), calcd
for C18H18NS2 312.0881, found 312.0885.
Supplementary data
NMR and 13C NMR of compounds 11, 15, 18 and 19 COSY 45 and
HSQC or HMBC spectra to support the assignments.
Supplementary dataassociated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.12.
118.
References and notes
11. 2,2-(2-Adamantyl)benzo[d][1,3]dithiole (18). Solid mp: 103.0–103.1 °C. 1H NMR:
d = 1.75–1.78 (m, 6H); 1.88 (m, 2H); 2.19–2.22 (m, 4H); 2.48 (m, 2H); 6.96–
6.98 (dd, Jorto = 6, Jmeta = 3, 2H); 7.15–7.17 (dd, Jorto = 6, Jmeta = 3, 2H) ppm. 13C
NMR: d = 26.6; 35.3; 37.6; 39.8; 122.1; 125.0; 138.1 ppm. MS (EI+), m/z
(relative intensity), 274 (M+, 64); 231 (8); 179 (11); 153 (100); 91 (12); 77
(11). HRMS (M+), calcd for C16H18S2 274.0850, found 274.0861.
1. (a) Larock, R. C. Comprehensive Organic Transformations, 2nd ed.; Wiley-VCH:
New York, 1999; (b) Yamamura, S.; Nishiyama, S. Comprehensive Organic
Synthesis In Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; pp
307–325. Vol. 8; (c) Hutchins, R. O.; Hutchins, M. K. Comprehensive Organic
Synthesis In Trost, . M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; pp
327–362. Vol. 8.
12. 2-Adamantyl-2-methylbenzo[d][1,3]dithiole (19). Solid mp: 122.9–123 °C. 1H
NMR: d = 1.62–1.71 (m, 6H); 1.84–1.85 (m, 6H); 1.91 (s, 3H); 2.06 (m, 3H);
6.95–6.97 (dd, Jorto = 6, Jmeta = 3, 2H); 7.13–7.15 (dd, Jorto = 6, Jmeta = 3, 2H) ppm.
13C NMR: d = 26.9; 28.7; 36.6; 38.6; 40.7; 80.02; 122.1; 124.9; 137.9 ppm. MS
(EI+), m/z (relative intensity), 302 (M+, 6); 268 (7); 209 (9); 167 (100); 134 (10).
HRMS (MH+), calcd for C18H23S2 303.1236, found 303.1195.
2. March, J. Advances in Organic Chemistry In Smith, M. B., March, J., Eds., 6th ed.;
John Wiley& Sons: New Jersey, 2007; pp 1835–1990.
3. Oksdath-Mansilla, G.; Peñéñory, A. B. J. Phys. Org. Chem. 2011, 24, 1136–1143.
4. Representative experimental procedure for the reduction process: these reactions
were carried out in a 10 mL three-necked Schlenk tube, equipped with a
nitrogen gas inlet and a magnetic stirrer. The tube was dried under vacuum,
filled with nitrogen and then with dried DMSO (10 mL). tert-BuOK (336.7 mg,