Transition-Metal-Free Reduction of α-Keto Thioesters with Hydrosilanes at Room Temperature: Divergent Synthesis through Reagent-Controlled Chemoselectivities

Article abstract of DOI:10.1002/adsc.201900222

The combination of hydrosilanes with a Br?nsted or Lewis acid as a promoter can be used for the reagent-controlled chemoselective reduction at room temperature of conjugated C=C bond, enone moiety, or the carbonyl of (β,γ-unsaturated) α-keto thioesters, providing facile access to β,γ-saturated α-keto thioesters, α-hydroxy thioesters, or silyl ethers. The reaction pathway and the chemoselectivity can be fine-tuned through the judicious choice of the hydrosilane or the reaction conditions. The reactions tolerate a wide range of functional groups including labile thioesters and the products are generally obtained in moderate to excellent yields. Unsymmetrical thioethers can also be synthesized using PMHS and catalytic B(C₆F₅)₃ via reductive deoxygenation of both the carbonyl groups. The applicability has been highlighted by the amine-mediated and coupling reagent-free syntheses of saturated α-keto amides from β,γ-unsaturated α-hydroxy thioesters and β,γ-saturated α-keto thioesters. (Figure presented.).

Full text of DOI:10.1002/adsc.201900222

Title: Transition-Metal-Free Reduction of α-Keto Thioesters with
Hydrosilanes at Room Temperature: Divergent Synthesis through
Reagent-Controlled Chemoselectivities
Authors: Rajib Maity, Bhanuranjan Das, and INDRAJIT DAS
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201900222
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10.1002/adsc.201900222
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201
Transition-Metal-Free Reduction of α-Keto Thioesters with
Hydrosilanes at Room Temperature: Divergent Synthesis
through Reagent-Controlled Chemoselectivities
Rajib Maity,a Bhanuranjan Das,a and Indrajit Dasa,*
a
Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road,
Jadavpur, Kolkata 700032, India
Fax: (+91)-33-2473-5197; e-mail: indrajit@iicb.res.in
Received:
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. The combination of hydrosilanes with a Brønsted or Lewis acid as a promoter can be used for the reagent-
controlled chemoselective reduction at room temperature of conjugated C=C bond, enone moiety, or the carbonyl of
(β,γ-unsaturated) α-keto thioesters, providing facile access to β,γ-saturated α-keto thioesters, α-hydroxy thioesters, or
silyl ethers. The reaction pathway and the chemoselectivity can be fine-tuned through the judicious choice of the
hydrosilane or the reaction conditions. The reactions tolerate a wide range of functional groups including labile
thioesters and the products are generally obtained in moderate to excellent yields. Unsymmetrical thioethers can also
be synthesized using PMHS and catalytic B(C6F5)3 via reductive deoxygenation of both the carbonyl groups. The
applicability has been highlighted by the amine-mediated and coupling reagent-free syntheses of saturated α-keto
amides from β,γ-unsaturated α-hydroxy thioesters and β,γ-saturated α-keto thioesters.
Keywords: α-Keto thioesters; Reduction; Chemoselective; Hydrosilylation; Lewis acids
activated by Brønsted[9] and Lewis acids,[10] or
Introduction
bases,[11] or by transition metals.[12] More importantly,
their reactivity can be fine-tuned by changing the
substituents on the silicon atom. We were therefore
attracted by the possibility of using inexpensive and
commercially available hydrosilanes for the
chemoselective reduction of the conjugated C=C
bond or keto group of β,γ-unsaturated α-keto
thioesters,[13] which may lead to the formation of
valuable synthetic intermediates.
α-Hydroxy or keto thioesters are expedient
intermediates for functional group transformations
and have long been of interest to synthetic organic
chemists.[1] They are often found as intermediates in
biochemical processes, such as in acetyl group
transfer reactions assisted by coenzyme A[2] and the
native chemical ligation (NCL) method to connect
peptides.[3] These processes are facilitated due to the
greater reactivity towards nucleophiles of thioesters
compared to oxoesters, ascribed to the smaller orbital
overlap between the sulfur atom and the carbonyl
group in the former. Notwithstanding the usefulness
of α-hydroxy or keto thioesters either as synthetic
intermediates or in pharmaceutical products,[4] their
widespread application has been hamstrung by the
lack of a general method for synthesis.
Herein we describe the transition metal and base-
free,[14] reagent-controlled chemoselective reduction
of various functionalities of β,γ-unsaturated α-keto
Since β,γ-unsaturated α-keto thioesters are easy
to synthesise, methods for their selective reduction
hold promise for easy access of α-hydroxy or keto
thioesters. The selective reduction of C-C double
bonds and ketones to C-C single bonds and alcohols
is indeed an important transformation in organic
chemistry.[5] But common reducing agents such as
molecular hydrogen,[6] aluminium hydrides and
borohydrides[7] often suffer from low selectivity in
the presence of other more reducible functional
groups. On the other hand, hydrosilanes are mild,
practical, and selective reducing agents[8] that can be
Scheme 1. Chemoselective reduction of (β,γ-unsaturated)
α-keto thioesters using hydrosilanes at room temperature.
1
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10.1002/adsc.201900222
Advanced Synthesis & Catalysis
thioesters under hydrosilylation conditions at room
temperature (Scheme 1). The reaction pathway and
the chemoselectivity can be controlled by judicious
choice of the reaction conditions. For example,
preferential reduction of the C=C bond may be
effected with PhMe2SiH in TFA, while that of the α-
keto group to hydroxy may be brought about by
Et3SiH in BF3.OEt2. Moreover, aryl or alkyl
substituted α-keto thioesters may undergo selective
keto reduction either with Et3SiH in TFA or with
various hydrosilanes in presence of catalytic
B(C6F5)3.[15] On the other hand, reductive
deoxygenation of both the carbonyl groups may be
performed using PMHS and catalytic B(C6F5)3,
offering a method to synthesize unsymmetrical
thioethers.
hydrosilane to 3 equiv resulted in a complete
reduction of the conjugated enone to furnish the
saturated α-hydroxy thioester (3a) in good yield
(entry 4). Next we tried to use Et3SiH as the hydride
source, but this furnished 3aa and 4a in low yields in
place of 2a or 3a (entry 5). However, replacing the
Brønsted with a Lewis acid (BF3.OEt2) afforded 4a in
moderate yields, enhanced further by changing the
amount of Et3SiH to 2.5 equiv (entry 7). Other
hydrosilanes, such as PhMe2SiH showed some
activity but gave significantly lower yields (entry 8),
while TMDS was completely inactive (entry 9).
Under the optimal reaction conditions (entry 3,
Table 1), the substrate scope and generality for the
chemoselective reduction of the conjugated C=C
bond in presence of thioester and keto group was
investigated. As shown in Table 2, β,γ-unsaturated α-
keto thioesters carrying aromatic, heterocyclic, or
fused aryl rings at the γ-position were selectively
reduced with 1 equiv of PhMe2SiH in TFA at ambient
temperature in moderate to good yields within a
minute (2a-o). Substrates having alicyclic or aliphatic
groups at the same position were also found to be
compatible under the standard reaction conditions
(2p-q). Notably, replacement of the thioester group
with an oxoester was also feasible, furnishing the
expected products (2r-s) in moderate yields.[16] It is
Results and Discussion
To optimize the reaction conditions for the
chemoselective reductions of the conjugated C=C
bond or the keto group of enones, a combination of
commercially available hydrosilane and a Brønsted or
Lewis acid was reacted with 1a as a model substrate
(Table 1; see also the Supporting Information). The
starting materials were completely decomposed
within two minutes in the presence of
Polymethylhydrosiloxane (PMHS) as a hydride
source and trifluoroacetic acid (TFA) as the promoter
(entry 1), ascribed to the difficulty in precise
determination of actual hydride content in PMHS.[8f]
But we were pleased to observe that
tetramethyldisiloxane (TMDS), containing two
proximal Si-H bonds, could reduce the conjugated
double bond selectively in TFA to furnish saturated
α-keto thioester (2a) in 60% yield (entry 2). The best
yield with high chemoselectivity was achieved with 1
equiv of PhMe2SiH, affording 2a in 83% yield within
a minute (entry 3). Further increase in the amount of
Table 2. Chemoselective reduction of the conjugated C=C
bond for accessing β,γ-saturated α-keto thioesters and
esters.[a]
Table 1. Optimization studies for 2a, 3a, and 4a.[a]
[a]
Reaction Conditions: 1a (0.05 g, 0.21 mmol, 1.0 equiv)
[a]
under the reaction conditions at rt (25 - 30 oC). n.d. = not
detected.
Reaction conditions: 1 (0.05 g, 1.0 equiv), PhMe2SiH
(1.0 equiv), trifluoroacetic acid (1.0 mL), rt (25 - 30 C)
o
[b] Starting material decomposed.
[c] Starting material recovered.
for 1-2 min.
[b] The reaction was carried out in 2 mmol batch size.
2
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10.1002/adsc.201900222
Advanced Synthesis & Catalysis
interesting to note that functional groups that are
vulnerable to reducing conditions, such as thioester,
keto, oxoester, acetoxy, and C(sp2)-halogen bonds
were unaffected, highlighting the mildness and
versatility of the method. Additionally, a gram-scale
experiment could be performed to isolate 2a in good
yields without special precautions (Table 2).
Table 4. Switched chemoselectivity in reduction of the
keto group of β,γ-unsaturated α-keto thioesters.[a]
We next examined the scope and viability of the
conjugated enone reduction (Table 3). Under the
optimized reaction conditions (Table 1, entry 4), a
range of β,γ-unsaturated α-keto thioesters bearing
aromatic rings at γ-position underwent smooth
conversion to saturated α-hydroxythioesters in good
yields (3a-g). The 3-thienyl substituted thioester also
furnished the expected product 3h, albeit in moderate
yields. Even a β,γ-unsaturated α-keto thioester
substituted with an alkyl group at γ-position proved
amenable to the reduction (3i).
Table 3. Reduction of the conjugated enone for accessing
β,γ-saturated α-hydroxy thioesters.[a]
[a]
Reaction conditions: 1 (0.05 g, 1.0 equiv), Et3SiH (2.5
equiv), BF3.OEt2 (1.0 equiv), dry DCM (1.5 mL), rt, 15 -
40 min.
Along with the products 4 and the unreacted starting
[b]
materials 1, minor amounts of compounds 2 and 3 were
also formed.
Encouraged by the above results, we extended the
possibility of the reduction of the α-keto group with
aryl- or alkyl-substituted α-keto thioesters rather than
styryl-substituted ones (Table 5). Optimization with
Table 5. Chemoselective reduction of the keto group of α-
keto thioesters using Et3SiH in TFA.[a]
[a]
Reaction conditions: 1 (0.05 g, 1.0 equiv), PhMe2SiH
(3.0 equiv), TFA (1.0 mL), rt.
We next investigated the substrate scope for the
considerably more challenging chemoselective
reduction of the keto group of β,γ-unsaturated α-keto
thioesters with Et3SiH in BF3.OEt2 (entry 7, Table 1)
in the presence of conjugated C-C double or triple
bond and thioester group (Table 4). Substrates
containing electron-withdrawing substituents in the
aromatic ring delivered the corresponding products
(4a-h) in good to nearly quantitative yields. However,
the presence of an electron-donating group in the
aromatic ring decreased the yield to 40% (4i). The
outcome may be ascribed to the decrease in
electrophilicity of the carbonyl group. The same trend
was also observed in case of phenyl, naphthyl, or
alkyl (-CH2CH2Ph) substituents at the γ-position of
β,γ-unsaturated α-hydroxy thioesters (4j-l). However,
a β,γ-alkynyl derivative was found to be compatible
to the reaction, and delivered the product (4m) in
excellent yields.
[a]
Reaction Condition: 5 (0.05 g, 1.0 equiv), Et3SiH (2.0
equiv), and trifluoroacetic acid (1.0 mL), rt.
The reaction was carried out in 1.8 mmol batch
[b]
size.
3
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10.1002/adsc.201900222
Advanced Synthesis & Catalysis
different hydrosilanes and a promoter showed that 2
equiv of Et3SiH in TFA can be used for accessing α-
hydroxy thioesters 6 with high selectivity (see the
Supporting Information). As summarized in Table 5,
regardless of the electronic properties of the
substituents in the aryl- or alkyl- group at the α-
position or in the thiol component of α-keto thioesters,
products 6a-o were always obtained in good to nearly
quantitative yields. Even thioesters containing α-alkyl
substituents delivered the corresponding products
smoothly (6p-r).
the alkylation of thiols under basic conditions.[18e] We
envision that these transition metal- and base-free
reaction conditions will be complementary to the
existing methods, particularly for the synthesis of
base-sensitive compounds.
Table 7. Synthesis of unsymmetrical thioethers via
reductive deoxygenation of the carbonyl groups.[a]
During the optimization studies on 6a, we observed
that adding 1 mol% of B(C6F5)3 to a DCM solution of
5a containing 2 equiv of Et3SiH, resulted in the
chemoselective formation of the silyl ether of the α-
hydroxy thioester (7a) within a minute. This
encouraged us to undertake a thorough investigation
(Table 6) to find that replacement of the Et3SiH with
other hydrosilanes also delivered the corresponding
silyl ether products in good to excellent yields (7b-d).
Even a thioester bearing a tert-butyl group at the α-
position was also found to be compatible for the
reaction (7e). The generality of this redction was
further explored with triethylsilane as the hydride
source (7f-k). Not surprisingly, an anisole derivative
[a]
Reaction Condition: 5 (0.05 g, 1.0 equiv), PMHS (2.0
equiv), B(C6F5)3 (1 mol%), DCM.
The synthetic utility of the developed β,γ-
unsaturated α-hydroxy thioesters 4 was demonstrated
by metal- and coupling reagent-free, primary or
secondary amine-mediated synthesis of β,γ-saturated
α-keto amides (9a-g) in good to nearly quantitative
yields (Scheme 2). Based on earlier reports, the
reaction is believed to proceed through the amine-
catalyzed isomerization of allylic alcohols[19] via Int-
I to Int-II, which underwent amidation to yield the
desired products. It is noteworthy that α-keto amides
(9a-b,c,f) could also be synthesized from β,γ-
saturated α-keto thioesters under the same optimized
conditions in good to excellent yields (Scheme 2).[20]
underwent
demethylation[17]
to
form
the
corresponding silyl ether derivative, along with
chemoselective hydrosilylation at the α-keto group
(7l).
Table 6. Chemoselective formation of the silyl ether
derivatives of α-hydroxy thioesters.[a]
Scheme 2. Amine-mediated syntheses of β,γ-saturated α-
keto amides from β,γ-unsaturated α-hydroxy thioesters 4
and β,γ-saturated α-keto thioesters 2.
[a]
Reaction Condition: 5 (0.05 g, 1.0 equiv), silane
reagents (2.0 equiv), B(C6F5)3 (1 mol%), dry DCM (1.0
mL), rt.
[b] 4.0 equiv Et3SiH and B(C6F5)3 (1 mol%) was used.
Interestingly, by replacing Et3SiH with PMHS as
the hydride source, we noticed the formation of
unsymmetrical thioethers (8a-f) in good to excellent
yields via reductive deoxygenation of the carbonyl
groups of the α-keto thioesters (Table 7).[18a-d]
Unsymmetrical thioethers are classically prepared by
4
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10.1002/adsc.201900222
Advanced Synthesis & Catalysis
o
1
solid (0.041 g, 81%); mp 49-51 C. H NMR (600 MHz,
CDCl3): δ = 7.25 (d, J = 8.4 Hz, 2 H), 7.14 (d, J = 8.4 Hz,
2 H), 4.24 (dd, J = 9.0, 4.2 Hz, 1 H), 2.85 (br. s., 1 H), 2.75
- 2.79 (m, 1 H), 2.71 - 2.75 (m, 1 H), 2.32 (s, 3 H), 2.10 -
2.16 (m, 1 H), 1.93 ppm (dtd, J = 14.4, 8.4, 6.0 Hz, 1 H);
13C{1H} NMR (150 MHz, CDCl3): δ = 204.3, 139.4, 131.9,
129.9 (2 CH), 128.6 (2 CH), 76.7, 36.6 (CH2), 30.3 (CH2),
11.2 ppm; IR (KBr): ṽmax = 3429, 1678, 1489, 1088, 814,
609 cm-1; HRMS (ESI): m/z calcd for C11H1335ClO2SNa [M
+ Na]+: 267.0226; found: 267.0226.
Conclusion
In conclusion, we have developed a reagent-
controlled highly chemoselective reduction of various
functionalities of β,γ-unsaturated α-keto thioesters at
room temperature. The reaction pathway can be
steered by the judicious choice of the reaction
conditions. The conjugated C=C bond can be
selectively reduced with PhMe2SiH in TFA, and the
α-keto group using Et3SiH in combination with
BF3.OEt2. Aryl or alkyl substituted α-keto thioesters
can be selectively reduced to α-hydroxy thioesters or
silyl ether derivatives under hydrosilylation
conditions in good to quantitative yields. On the other
hand, unsymmetrical thioethers can be synthesized
via reductive deoxygenation of both the carbonyl
groups with PMHS and catalytic B(C6F5)3. To
demonstrate the potentiality of the method, amine-
mediated and coupling reagent-free syntheses of
saturated α-keto amides from β,γ-unsaturated α-
hydroxy thioesters and β,γ-saturated α-keto thioesters
have also been carried out successfully.
General Procedure for the Synthesis of 4a-m: γ-
Substituted β,γ-unsaturated α-keto thioesters 1 (0.05 g, 1
equiv) were dissolved in dry DCM (1.0 mL), and triethyl
silane (Et3SiH; 2.5 equiv) and BF3.OEt2 (1.0 equiv) were
added successively to the reaction mixture which was
allowed to stir at the room temperature for 15-40 min
under argon atmosphere. After completion of the reaction
(TLC), water was added, and the product was extracted
with DCM. The combined organic layers were dried over
anhydrous Na2SO4 and filtered, and the filtrate was
concentrated under reduced pressure to get a residue. The
crude residue was purified by silica gel column
chromatography [230−400; eluent: ethyl acetate/n-hexane]
to obtain 4a-m.
S-methyl
(E)-4-(4-chlorophenyl)-2-hydroxybut-3-
enethioate 4a: Prepared according to the general
procedure discussed above: Rf = 0.3; eluent, EtOAc/n-
hexane (15%); light yellow liquid (0.043 g, 85%). 1H
NMR (600 MHz, CDCl3): δ = 7.32 (d, J = 9.0 Hz, 2 H),
7.29 (d, J = 8.4 Hz, 2 H), 6.76 (dd, J = 15.6, 0.6 Hz, 1 H),
6.20 (dd, J = 15.6, 6.6 Hz, 1 H), 4.89 (dd, J = 0.6, 6.6 H, 1
H), 3.41 (br. s., 1 H), 2.35 ppm (s, 3 H); 13C{1H} NMR
(150 MHz, CDCl3): δ = 202.0, 134.4, 134.0, 132.7, 128.9
(2 CH), 128.0 (2 CH), 125.9, 78.5, 11.5 ppm; IR (KBr):
ṽmax = 3429, 1678, 1489, 1088, 968, 814 cm-1; HRMS
(ESI): m/z calcd for C11H1235ClO2S [M + H]+: 243.0246;
found: 243.0250 and C11H1237ClO2S [M + H]+: 245.0217;
found: 245.0220.
Experimental Section
General Procedure and Representative Examples
General Procedure for the Synthesis of 2a-p: γ-
Substituted β,γ-unsaturated α-keto thioesters 1 (0.05 g, 1
equiv) were dissolved in trifluoroacetic acid (1.0 mL).
Then dimethylphenylsilane (PhMe2SiH; 1.0 equiv) was
added to the reaction mixture which was allowed to stir at
the room temperature for 1-2 min under argon atmosphere.
After completion of the reaction (TLC), water was added,
and the product was extracted with DCM. The combined
organic layers were dried over anhydrous Na2SO4 and
filtered, and the filtrate was concentrated under reduced
pressure to get a residue. The crude residue was purified
using silica gel column chromatography [230−400; eluent:
ethyl acetate/n-hexane] to obtain 2a-p.
General Procedure for the Synthesis of 6a-r: α-Keto
thioesters
5 (0.05 g, 1 equiv) were dissolved in
trifluoroacetic acid (1.0 mL), and triethyl silane (Et3SiH;
2.0 equiv) was added to the reaction mixture which was
allowed to stir at the room temperature for 20-30 min
under argon atmosphere. After completion of the reaction
(TLC), water was added, and the product was extracted
with DCM. The combined organic layers were dried over
anhydrous Na2SO4 and filtered, and the filtrate was
concentrated under reduced pressure to get a residue. The
crude residue was purified by silica gel column
chromatography [230−400; eluent: ethyl acetate/n-hexane]
to obtain 6a-r.
S-methyl 4-(4-chlorophenyl)-2-oxobutanethioate 2a:
Prepared according to the general procedure discussed
above: Rf = 0.3; eluent, EtOAc/n-hexane (2%); yellow
1
liquid (0.042 g, 83%). H NMR (300 MHz, CDCl3): δ =
S-phenyl 2-(4-bromophenyl)-2-hydroxyethanethioate
6b: Prepared according to the general procedure discussed
above: Rf = 0.3; eluent, EtOAc/n-hexane (10%); light
7.25 (d, J = 8.4 Hz, 2 H), 7.13 (d, J = 8.4 Hz, 2 H), 3.13 (t,
J = 7.8 Hz, 2 H), 2.92 (t, J = 6.9 Hz, 2 H), 2.34 ppm (s, 3
H); 13C{1H} NMR (75 MHz, CDCl3): δ = 193.9, 191.6,
138.4, 132.1, 129.7 (2 CH), 128.6 (2 CH), 37.9 (CH2), 28.2
(CH2), 11.2 ppm; IR (KBr): ṽmax = 1720, 1667, 1492, 1091,
847, 814, 741 cm-1; HRMS (ESI): m/z calcd for
C11H1135ClO2SNa [M + Na]+: 265.0066; found: 265.0061.
o
1
yellow solid (0.046 g, 91%); mp 77-79 C. H NMR (600
MHz, CDCl3): δ = 7.55 (d, J = 8.4 Hz, 2 H), 7.39 - 7.44 (m,
3 H), 7.35 - 7.37 (m, 4 H), 5.29 (s, 1 H), 3.72 ppm (br. s., 1
H); 13C{1H} NMR (150 MHz, CDCl3): δ = 200.0, 136.6,
134.6 (2 CH), 132.0 (2 CH), 129.8, 129.4 (2 CH), 128.8 (2
CH), 126.2, 123.2, 79.3 ppm; IR (KBr): ṽmax = 1690, 1480,
968, 834, 792 cm-1; HRMS (ESI): m/z calcd for
C14H1179BrO2SNa [M + Na]+: 344.9561; found: 344.9544
and m/z calcd for C14H1181BrO2SNa [M + Na]+: 346.9541;
found: 346.9521.
General Procedure for the Synthesis of 3a-i: γ-
Substituted β,γ-unsaturated α-keto thioesters 1 (0.05 g, 1
equiv) were dissolved in trifluoroacetic acid (1.0 mL), and
dimethylphenyl silane (PhMe2SiH; 3.0 equiv) was added to
the reaction mixture that was allowed to stir at the room
temperature for 15-30 min under argon atmosphere. After
completion of the reaction (TLC), water was added, and
the product was extracted with DCM. The combined
organic layers were dried over anhydrous Na2SO4 and
filtered, and the filtrate was concentrated under reduced
pressure to get a residue. The crude residue was purified by
silica gel column chromatography [230−400; eluent: ethyl
acetate/n-hexane] to obtain 3a-i.
General Procedure for the Synthesis of 7a-l: α-Keto
thioesters 5 (0.05 g, 1 equiv) were dissolved in dry DCM
(1.0 mL), and various silanes - Et3SiH, PhMe2SiH,
EtMe2SiH, and Et2MeSiH (2.0 equiv) and B(C6F5)3 (1
mol%) were added successively to the reaction mixture
and allowed to stir at the room temperature for 1 min under
argon atmosphere. After completion of the reaction (TLC),
water was added, and the product was extracted with DCM.
The combined organic layers were dried over anhydrous
Na2SO4 and filtered, and the filtrate was concentrated
under reduced pressure to get a residue. The crude residue
S-methyl 4-(4-chlorophenyl)-2-hydroxybutanethioate
3a: Prepared according to the general procedure discussed
above: Rf = 0.3; eluent, EtOAc/n-hexane (10%); colourless
5
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10.1002/adsc.201900222
Advanced Synthesis & Catalysis
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Yamashita, S.-C. Lin, L. Li, T. Fukuyama, J. Braz.
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[230−400; eluent: ethyl acetate/n-hexane] to obtain 7a-l.
S-phenyl
2-phenyl-2-((triethylsilyl)oxy)ethanethioate
7a: Prepared according to the general procedure discussed
above: Rf = 0.3; eluent, EtOAc/n-hexane (2%); colourless
1
liquid (0.061 g, 82%). H NMR (400 MHz, CDCl3): δ =
7.51 (d, J = 7.2 Hz, 2 H), 7.30 - 7.37 (m, 8 H), 5.27 (s, 1
H), 0.97 - 1.01 (m, 9 H), 0.65 - 0.72 ppm (m, 6 H);
13C{1H} NMR (100 MHz, CDCl3): δ = 201.5, 139.0, 134.8
(2 CH), 129.1 (2 CH), 129.1 (2 CH), 128.5 (2 CH), 128.4,
126.4 (2 CH), 80.5, 6.8 (3 CH3), 4.8 ppm (3 CH2); IR
(KBr): ṽmax = 1703, 1125, 1053, 1001, 742, 701, 687 cm-1;
HRMS (ESI): m/z calcd for C20H27O2SSi [M + H]+:
359.1501; found: 359.1491 and m/z calcd for
C20H26O2SSiNa [M + Na]+: 381.1321; found: 381.1308.
General Procedure for the Synthesis of 8a-f: α-Keto
thioesters 5 (0.05 g, 1 equiv) were dissolved in dry DCM
(1.0 mL), and polymethylhydrosiloxane (PMHS; 2.0
equiv) and B(C6F5)3 (1 mol%) were added successively to
o
the reaction mixture at 0 C under argon atmosphere. The
reaction mixture was allowed to stir at the room
temperature for 5 min. After completion of the reaction
(TLC), water was added, and the product was extracted
with DCM. The combined organic layers were dried over
anhydrous Na2SO4 and filtered, and the filtrate was
concentrated under reduced pressure to get a residue. The
crude residue was purified using silica gel column
chromatography [230−400; eluent: ethyl acetate/n-hexane]
to obtain 8a-f.
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(2,4-dimethylphenethyl)(phenyl)sulfane 8d: Prepared
according to the general procedure discussed above: Rf =
0.3; eluent, n-hexane (100%); colourless liquid (0.03 g,
67%). 1H NMR (300 MHz, CDCl3): δ = 7.38 (d, J = 7.5 Hz,
2 H), 7.30 (t, J = 6.9 Hz, 2 H), 7.20 (t, J = 7.2 Hz, 1 H),
7.04 (d, J = 7.5 Hz, 1 H), 6.95 - 6.98 (m, 2 H), 3.10 (t, J =
8.7 Hz, 2 H), 2.89 (t, J = 8.7 Hz, 2 H), 2.29 (s, 3 H), 2.24
ppm (s, 3 H); 13C{1H} NMR (75 MHz, CDCl3): δ = 136.4,
136.1, 135.7, 135.3, 131.1, 129.2 (2 CH), 129.0, 128.9 (2
CH), 126.7, 125.9, 34.0 (CH2), 32.7 (CH2), 20.9, 19.1 ppm;
IR (KBr): ṽmax = 1442, 1261, 1026, 802, 736 cm-1; HRMS
(ESI): m/z calcd for C16H18SNa [M + Na]+: 265.1027;
found: 265.1023.
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Boro-hydrides in Organic Synthesis, 2nd ed., Wiley,
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1998, 27, 395.
Acknowledgements
[8] a) B. Marciniec, J. Gulinsky, W. Urbaniak, Z. W.
Kornetka
in
Comprehensive
Handbook
on
Financial support for this work was provided by DST-SERB
(EMR/2016/001720). R.M. thanks UGC-India and B.R.D. thanks
NIPER-Kolkata for their fellowships. We thank Dr. Basudeb
Achari for helpful discussions.
Hydrosilylation, (Ed.: B. Marciniec), Pergamon,
Oxford, 1992; b) D. Addis, S. Das, K. Junge, M. Beller,
Angew. Chem. Int. Ed. 2011, 50, 6004; Angew.
Chem. 2011, 123, 6128; c) T. Liu, X. Wang, D. Yin,
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7
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Advanced Synthesis & Catalysis
FULL PAPER
Transition-Metal-Free Reduction of α-Keto
Thioesters with Hydrosilanes at Room
Temperature: Divergent Synthesis through
Reagent-Controlled Chemoselectivities
Adv. Synth. Catal. Year, Volume, Page – Page
Rajib Maity, Bhanuranjan Das, and Indrajit Das*
8
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