Indium(0)-mediated Csp 3-S/O cross-coupling approach towards the regioselective alkylation of α-enolic esters/dithioesters: A mechanistic Insight

Article abstract of DOI:10.1002/ejoc.201301788

We have reported an indium(0)-mediated C_sp3-S/O cross-coupling approach that leads to the highly regioselective alkylation of α-enolic acetate/dithioacetate systems. This hetero cross-coupling reaction does not require additional co-catalyst or promoter, and the in situ generated organoindium species promotes the reaction by acting as the coupling partner of the α-enolic acetate/dithioacetate substrates. The excellent selectivity for C-, S-, or O-alkylation is solely dependent on the nucleophilic behavior of α-enolic acetate/dithioacetate systems. These results were further supported by DFT calculations of the relative electronic energies of the substrates and products as well as the activation barriers of the respective transformations.

Full text of DOI:10.1002/ejoc.201301788

FULL PAPER
DOI: 10.1002/ejoc.201301788
3
Indium(0)-Mediated Csp –S/O Cross-Coupling Approach Towards the
Regioselective Alkylation of α-Enolic Esters/Dithioesters: A Mechanistic
Insight
Sushobhan Chowdhury,[a] Tanmoy Chanda,[a] Ashutosh Gupta,[b] Suvajit Koley,[a]
B. Janaki Ramulu,[a] Raymond C. F. Jones,[c] and Maya Shankar Singh*[a]
Keywords: Synthetic methods / Cross-coupling / Regioselectivity / Indium / Alkylation / Allylation
We have reported an indium(0)-mediated Csp3–S/O cross-
coupling approach that leads to the highly regioselective alk-
ylation of α-enolic acetate/dithioacetate systems. This hetero
cross-coupling reaction does not require additional co-cata-
lyst or promoter, and the in situ generated organoindium spe-
cies promotes the reaction by acting as the coupling partner
of the α-enolic acetate/dithioacetate substrates. The excel-
lent selectivity for C-, S-, or O-alkylation is solely dependent
on the nucleophilic behavior of α-enolic acetate/dithioacetate
systems. These results were further supported by DFT calcu-
lations of the relative electronic energies of the substrates
and products as well as the activation barriers of the respec-
tive transformations.
philes[3e–3g] have been utilized in several synthetic opera-
tions.[4] Moreover, organoindium reagents can act as an ef-
fective nucleophilic coupling partner in Pd-catalyzed cross-
coupling reactions.[2,5,6] Ranu and co-workers[7] performed
a cross-coupling reaction of allylindium reagents with acti-
vated benzylic bromides. However, examples of organoind-
ium species in coupling reactions in the absence of other
promoters are rare and remain unexplored.
Herein, we disclose a hitherto unreported regioselective
alkylation that proceeds through a Csp3–S/O cross-coupling
reaction of an α-enolic acetate/dithioacetate system with an
alkylindium reagent. In the initial reaction step, indium(0)
forms an organoindium species with the alkyl halide, which
undergoes a coupling reaction with the α-enolic ester/di-
thioester that is present in the system. Upon quenching the
reaction, a regioselectively alkylated product is exclusively
formed. The regioselectivity of the alkylation step is di-
rected by the relative electronic energies of the respective
species and the activation barriers of the transformation, as
evident from the DFT calculations of the energies, which
were performed on the respective systems.
Introduction
During the last century, organometallic reagents such as
organolithium, organotin, organozinc, organolead, and or-
ganomagnesium compounds have played a key and vital
role in the progress of organic synthesis.[1] However, these
reactive reagents are highly sensitive to moisture and air
and demonstrate poor compatibility towards carbonyl and
hydroxy groups, thus, limiting their widespread application
in organic synthesis. Consequently, organoindium rea-
gents[2] have recently emerged as an attractive alternative to
these organometallic species because of their mild, nontoxic
nature, relative stability, and excellent tolerance towards
various functional groups. Additionally, the use of organo-
indium reagents in an aqueous medium is remarkable from
both economic and environmental standpoints,[2a] two fac-
tors indicative of a successful approach. The attractive fea-
tures of organoindium reagents lead to better performance
and selectivity in comparison to other organometallic rea-
gents, which suffer from significant limitations in organic
synthesis. The use of indium(0) metal in allylation, proparg-
ylation, and analogous reactions is widely described.[3a–3d]
Organoindium compounds as a source of alkyl nucleo-
[a] Department of Chemistry, Faculty of Science, Banaras Hindu
University,
Results and Discussion
Varanasi 221005, India
It has been established from spectroscopic (IR and
NMR) data and single-crystal X-ray diffraction analysis
that a β-oxodithioester solely exists as its enolic tautomer
in both the solid[8a] as well as the solution phase. DFT stud-
ies that employ the B3LYP method with a 6-31G* basis set
also suggest that the α-enolic form is 2.52 kcalmol–1 more
stable (stabilized by intramolecular hydrogen bonding) than
E-mail: mssinghbhu@yahoo.co.in
http://www.drmssinghchembhu.com/
[b] Department of Chemistry, Udai Pratap Autonomous College,
Kashi Vidyapeeth University,
Varanasi 221005, India
[c] Department of Chemistry, Loughborough University,
Loughborough, Leics, LE11 3TU, UK
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301788.
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Indium(0)-Mediated Csp3–S/O Cross-Coupling Approach
the β-oxo form. Therefore, we began our investigation by dered the reaction (see Table 1, Entries 3–8). Obviously,
assuming that the α-enolic form was the reactive species.
screening the solvents revealed that DMF was the appropri-
The synthetic utility of α-enolic dithioesters has already ate solvent, as it not only resulted in a shorter reaction time,
been explored by our group,[8b,8c] but we were further inter- but also provided the highest yield (see Table 1, Entry 1).
ested in the chemistry of their allylated derivatives. In a re- Next, InCl3 was used as the mediator instead of In0 powder.
cent report,[9a] we found that the treatment of an α-enolic Unfortunately, the efficiency of InCl3 to mediate the reac-
dithioester with a Grignard reagent generated a tertiary tion was inferior to that of metallic indium (see Table 1,
alcohol through a nucleophilic attack at the enolic β-car- Entries 9 and 10). Consequently, other metals such as Zn
bon. Similar results were also observed with alkyllithium and Cu (1.2 mmol in each case) were employed, but they
reagents.[9b] We, therefore, postulated that the treatment of could not promote the reaction (see Table 1, Entries 11 and
an α-enolic dithioester with an in situ generated allylic in- 12). In the absence of a mediatior, the reaction did not pro-
dium species[2,10] should also undergo allylation at the β- vide any product, even in a trace amount, after 48 h (see
carbon of the dithioester through a nucleophilic addition. Table 1, Entry 13).
However, the treatment of α-enolic dithioester 1 with in-
dium(0) powder and allyl halide 2 in N,N-dimethylform-
Table 1. Optimization of the model allylation reaction.
amide (DMF) at room temperature provided the unexpec-
ted α-C-allylated product 3, instead of the expected β-C-
allylated product 3A (see Scheme 1). Previously, Ila and co-
workers[11] performed the α-C-allylation of a dithioester
with allyl bromide by employing a conventional base-cata-
lyzed nucleophilic substitution pathway. Herein, we
achieved the alkylation through Csp3–S cross-coupling reac-
tions of organoindium species with α-enolic dithioesters.
Until now, no examples have been reported of the α-C-allyl-
ation of a dithioester through a cross-coupling approach,
and to the best of our knowledge this is the first of its kind
to proceed through an organoindium pathway under neu-
tral, mild reaction conditions.
Entry Mediator Dithioester/ Solvent
Temp. Time
%
[equiv.]
RX
[h] Yield[a]
1
2
3
4
5
6
7
8
In (1.2)
In (1.2)
In (1.2)
In (1.2)
In (1.2)
In (1.2)
In (1.2)
In (1.2)
InCl3 (1.2)
InCl3 (1.2)
Zn (1.2)
Cu (1.2)
none
In (0.5)
In (0.75)
In (1.0)
In (1.5)
In (1.2)
In (1.2)
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
DMF
DMF
THF
r.t.
60
12
12
24
24
24
24
24
24
24
12
24
24
48
12
12
12
12
12
12
85
60
[b]
r.t.
–
THF
reflux
r.t.
trace
[b]
CH3CN
CH3CN
EtOH
EtOH
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
–
reflux
r.t.
10
[b]
–
reflux
r.t.
20
trace
40
9
10
11
12
13
14
15
16
17
18
19
80 °C
r.t.
[b]
–
–
–
[b]
r.t.
r.t.
[b]
r.t.
r.t.
40
60
75
80
68
82
r.t.
r.t.
1:0.75
1:1.2
r.t.
r.t.
[a] Isolated pure yields. [b] No reaction.
Next, to optimize the loading of the indium(0), different
experiments were performed (see Table 1, Entries 14–17).
The optimum loading of indium(0) was determined as
Scheme 1. Formation of γЈ-selective C-allylated products 3 from
allylic halides 2.
Initially, we treated methyl 3-hydroxy-3-phenylprop-2- 1.2 equiv. Finally, the ratio of allyl bromide to the dithioes-
enedithioate (1a, 1.0 mmol), with indium(0) powder ter was also varied, and a 1:1 ratio led to the maximum
(1.2 mmol) and allyl bromide (2a, 1.0 mmol) in DMF at yield (see Table 1, Entries 18 and 19). Consequently, the
room temperature. The reaction afforded α-C-allylated best results were achieved by employing a 1:1:1.2 ratio of
product 3a, that is, methyl 2-allyl-3-oxo-3-phenylpropanedi- the dithioester, allyl bromide, and indium(0) at room tem-
thioate, in 85% yield within 12 h with the full consumption perature for 12 h (for details of the optimization, see Sup-
of the starting materials. Encouraged by our initial results, porting Information).
we focused on the optimal reaction conditions (see Table 1).
With the optimal reaction conditions in hand, we com-
At an elevated temperature of 60 °C, the yield of the desired menced to explore the substrate scope and diversity of the
product decreased along with the generation of some ad- current protocol (see Table 2). The protocol was found to
ditional compounds, as indicated by the spots on TLC plate be γЈ specific, and as observed, a wide range of dithioesters
(see Table 1, Entry 2). Interestingly, changing the solvent and allyl halides were well tolerated. In all cases, the reac-
from more polar DMF to the comparatively less polar sol- tions proceeded smoothly to afford the corresponding prod-
vents like tetrahydrofuran (THF), CH3CN, and EtOH hin- ucts in good yields.
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Table 2. Substrate scope for the synthesis of C-allylated product.[a]
[a] 1 (1.0 mmol) and 2 (1.0 mmol) in presence of indium powder (1.2 mmol).
To broaden the scope of this protocol further, we focused is essentially an α-enolic ester that contains a permanent α-
on employing nonallylic halides. Surprisingly, no reaction enol part and, thus, has a fundamentally similar structure
took place at room temperature. However, a highly regiose- as an α-enolic dithioester. Stunningly, irrespective of the
lective S-alkylation reaction took place at 60 °C, and in- employed alkyl or allyl halide, a regioselective enolic O-alk-
stead of a C-alkylation to give 4, this reaction furnished α- ylation took place at 60 °C in all cases to lead to the syn-
oxoketene-S,S-acetals 5 in high yield within 12–24 h (see thetically useful enol-ether linkage 7 in excellent yields
Scheme 2). The structures of all of the α-oxoketene-S,S- within 6–12 h (see Scheme 3).[12b,13,14]
1
acetals 5 were identified by their IR, H NMR, 13C NMR,
and HRM spectra and unequivocally confirmed by the X-
ray single-crystal diffraction analysis of one of the represen-
tative compounds (5a).[12a]
Scheme 3. Regioselective synthesis of O-alkylated product 7 from
4-hydroxycoumarin (6).
To elucidate the probable structure of the organoindium
species, we analyzed the NMR spectra from some of our
initial experiments. Methyl 3-hydroxy-3-(p-tolyl)prop-2-en-
edithioate (1.0 mmol) was treated with indium(0) powder
Scheme 2. Synthesis of S-alkylated product 5 from nonallylic hal-
(1.2 mmol) in 5 mL of DMF, and the mixture was stirred
ides.
at room temperature. After 1 h, the NMR spectrum of the
Prompted by continuous observations of anomalous reaction mixture was recorded, in which there was no
trends, we attempted a parallel study of the cross-coupling change in the characteristic signals of the dithioester in
of alkylindium species with 4-hydroxycoumarin (6), which DMF. This suggested no formation of the initial organo-
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Indium(0)-Mediated Csp3–S/O Cross-Coupling Approach
indium species with the dithioester (see Supporting Infor- ium intermediate allylindium(III) dihalide A. In the next
mation).
step, the thioenol form of the dithioester (i.e., 1Ј) is inserted
Next, we treated allyl bromide (1.0 mmol) with indium(0) into A with the halide leaving to form B. Consequently, B
powder (1.2 mmol) in 5 mL of DMF and stirred the mix- undergoes a reductive C–S coupling to form α-oxoketene
ture at room temperature. In this case, the NMR spectrum dithioacetal 5. As soon as this is formed, 5 immediately
of the reaction mixture after 1 h displayed new resonances undergoes a facile [3,3] sigmatropic shift of the allylic
at δ = 2.12, 4.13, and 4.45 ppm. These signals correspond groups to give C-allylated product 3 under the influence of
to the organoindium intermediate allylindium(III) di- the organoindium species.
bromide as revealed by Araki et al.[10b] and also established
At this stage, the question with regard to the selectivity
by Chan et al.[10c] However, other probable intermediates of C-, S-, or O-alkylation still remains unanswered. To ra-
could not be assigned because their corresponding signals tionalize this anomaly through a logical thread, we em-
were not observed (see Supporting Information). Therefore, ployed DFT calculations. The calculations were performed
according to the observed NMR spectral pattern and litera- on isolated molecules without considering indium as part
ture reports,[10] we considered allylindium(III) dihalide A as of the system. As regioselectivity is observed in all the
the active organoindium species to participate in the cou- cases,[11,13] irrespective of the catalytic and solvent systems,
pling reaction.
only such an approach can give insight into the inherent
Although available reports of C–S cross-couplings of thi- electronic properties of the corresponding starting mo-
ols with alkyl/aryl halides do not provide details about a lecules from which the regioselective alkylation occurs.
precise reaction pathway,[15,16] we proposed a tentative
In case of the α-enolic dithioesters, there are three pos-
mechanism for the coupling phenomenon based on our ex-
perimental observations and literature reports (see
Scheme 4). The initial step is the formation of organoind-
sible points of alkylation, that is, the enolic oxygen atom,
the enolic carbon atom, and the thiocarbonyl sulfur of the
dithioacetate. In Figure 1, the DFT calculation shows a
large energy difference between the O-alkylated product
and the C-alkylated product (11.69 kcalmol–1), which rules
out the possibility of any O-alkylation taking place. The
S-alkylated product, however, shows only a minor energy
difference in comparison to the C-alkylated product
(1.94 kcalmol–1) and is compensated by the greater nucleo-
philicity and charge density of the S atom over the C atom
to favor the exclusive formation of the S-alkylated product.
For similar reasons, the S-allylation will occur first in the
allylation of the dithioester. In the next step, because of the
lability of the C–S bond, the S-allylated product will pass
through the comparatively low energy barrier of
22.30 kcalmol–1 and undergo a [3,3] sigmatropic shift at
room temperature to give the lower energy C-allylated
product 3 (see Figure 1). This type of [3,3] sigmatropic shift
Scheme 4. Proposed mechanism based on the spectral evidence.
Figure 1. Relative electronic state energies of ethylated and allylated products as well as the activation energy barrier of [3,3] sigmatropic
shift for α-enolic dithioesters 1.
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Figure 2. Relative electronic state energies of ethylated and allylated products as well as activation energy barrier of [3,3] sigmatropic
shift for 4-hydroxycoumarin (6).
cannot occur with nonallylic groups, and, in this case, the ists to deal with such systems. The allylated adducts have
reaction would, therefore, terminate at the S-alkylation step been further employed in the syntheses of different thio-
to give corresponding S-alkylated product.
heterocycles, which will be published at a later date.
In the case of the alkylation of 4-hydroxycoumarin, the
energy difference between the enolic O-alkylated product
and the C-alkylated product is 4.57 kcalmol–1. Thus, here
also the charge density factor predominates to guide the
reaction towards an enolic O-alkylation. The huge energy
difference of the product obtained by O-alkylation of the
ester carbonyl group (13.81 kcalmol–1), however, makes it
energetically more unstable, which rules out any possibility
of ester O-alkylation (see Figure 2). The stability of the all-
ylated product of 4-hydroxycumarin also follows the same
trend as the alkylation. Here, the possibility of a [3,3] sig-
matropic shift has been ruled out because of the greater
stability of C–O bond and relatively high activation energy
barrier of 29.40 kcalmol–1 (see Figure 2). Therefore, in case
of 4-hydroxycumarin, both the alkylation and allylation re-
actions terminated at the enolic O-alkylation step.
Experimental Section
General Methods: Commercially available alkyl and allyl halides,
indium powder, 4-hydroxycoumarin, and DMF were used as re-
ceived without further purification. The β-oxodithioesters were pre-
pared according to the literature procedure.[17] DFT studies were
performed by employing the B3LYP (Becke-3-parameter-Lee–
Yang–Parr) method with the 6-31G(d) basis set implemented in
Gaussian 09 for all structures. Geometrical parameters of reactants,
intermediates, transition states (TS), and products were fully opti-
mized in the gas phase (for isolated molecules). Thin layer
chromatography was performed with silica gel 60 F254 precoated
plates. Column chromatography was performed with 100–200 mesh
silica gel. Infrared spectra were recorded as KBr pellets, and the
frequencies are reported in cm–1. The 1H and 13C NMR spectro-
scopic data were recorded with a spectrometer that operated at
either 300 or 400 MHz and 75.5 or 100 MHz, respectively. Chemi-
cal shifts (δ) are given in parts per million (ppm) by using the resid-
ual solvent peaks as the reference relative to TMS. Coupling con-
stant (J) values are given in Hz. Mass spectra were recorded using
electrospray ionization mass spectrometry.
Conclusions
In summary, we have developed a facile indium(0)-medi-
ated regioselective alkylation protocol for α-enolic ester/di-
thioester systems that proceeds through a Csp3–S/O cross-
coupling reaction of alkylindium reagents and α-enolic es-
ters/dithioesters. A reasonable mechanism that describes the
overall reaction pathway has also been documented. The
alkylation trend was solely dependent on the structural and
chemical behavior of the substrate and alkylating reagent,
which was revealed by theoretical investigations done on
their relative electronic energies as well as the activation
barrier of the transformation. Thus, the concept of chemoe-
lectronic guidance, which was observed throughout the en-
General Procedure for the Synthesis of α-Allyl-β-oxodithioacetates
3a–3i: To a solution of α-enolic dithioester 1 (1.0 mmol) in DMF
(5 mL) were added indium powder (1.2 mmol) and allyl halide 2
(1.0 mmol), and the resulting mixture was stirred at room tempera-
ture for 12 h. Upon completion, the reaction was treated with di-
lute HCl solution followed by brine, and the mixture was extracted
with ethyl acetate (2ϫ 10 mL). The combined organic layers were
dried with anhydrous Na2SO4 and evaporated under vacuum. The
crude reaction mixture was purified by column chromatography
(hexane) to afford the pure α-allyl-β-oxodithioacetates 3.
Methyl 2-Benzoylpent-4-enedithioate (3a): Red oil (212 mg, 85%
1
tire course of the alkylation study, will certainly help chem- yield). H NMR (300 MHz, CDCl3): δ = 8.03 (d, J = 7.2 Hz, 2 H,
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Indium(0)-Mediated Csp3–S/O Cross-Coupling Approach
Ar), 7.53 (t, J = 7.2 Hz, 1 H, Ar), 7.44–7.39 (m, 2 H, Ar), 5.86–
(m, 1 H, CH2), 2.62 (s, 3 H, SMe) ppm. 13C NMR (75.5 MHz,
5.73 (m, 1 H, vinylic CH), 5.31 (t, J = 7.2 Hz, 1 H, tertiary CH), CDCl3): δ = 231.1 (C=S), 186.0 (C=O), 143.3, 134.8, 134.2, 133.1,
5.14–5.00 (m, 2 H, vinylic CH2), 3.09–2.99 (m, 1 H, CH2), 2.83– 128.2, 117.7, 69.2 (tertiary CH), 38.2 (CH2), 20.1 (SMe) ppm.
2.74 (m, 1 H, CH2), 2.58 (s, 3 H, SMe) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 231.7 (C=S), 193.2 (C=O), 136.0, 134.4, 133.2, 128.7,
Methyl 2-(Furan-2-carbonyl)pent-4-enedithioate (3h): Red oil
(204 mg, 85% yield, diastereomeric mixture). 1H NMR (300 MHz,
128.5, 117.4, 67.6 (tertiary CH), 38.3 (CH2), 19.9 (SMe) ppm. IR
CDCl3): δ = 7.60 (br., 1 H, Ar), 7.33 (d, J = 3.6 Hz, 1 H, Ar), 6.53
(KBr): ν = 2978, 2916, 1688, 1447, 1231, 921, 688 cm–1. HRMS:
˜
(br., 1 H, Ar), 5.83–5.70 (m, 1 H, vinylic CH), 5.14–5.01 (m, 3 H,
tertiary CH, vinylic CH2), 3.06–2.97 (m, 1 H, CH2), 2.83–2.74 (m,
1 H, CH2), 2.62 (s, 3 H, SMe) ppm. 13C NMR (75.5 MHz, CDCl3):
δ = 230.9 (C=S), 181.8 (C=O), 151.6, 147.0, (134.2, 134.1), 118.9,
117.6, (112.5, 112.3), (67.8, 67.6, CH), 37.6 (allylic CH2), 20.0,
calcd. for 251.0559 [M + H]+; found 251.0571.
Methyl 2-(4-Methoxybenzoyl)pent-4-enedithioate (3b): Red oil
1
(228 mg, 82% yield). H NMR (300 MHz, CDCl3): δ = 8.04 (d, J
= 8.7 Hz, 2 H, Ar), 6.91 (d, J = 9.0 Hz, 2 H, Ar), 5.83–5.74 (m, 1
H, vinylic CH), 5.29 (t, J = 7.2 Hz, 1 H, tertiary CH), 5.14–5.00
(m, 2 H, vinylic CH2), 3.85 (s, 3 H, OMe), 3.05–3.01 (m, 1 H,
CH2), 2.83–2.76 (m, 1 H, CH2), 2.60 (s, 3 H, SMe) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 232.2 (C=S), 191.7 (C=O), 163.6, 134.6,
131.2, 129.0, 117.3, 113.7, 67.6 (tertiary CH), 55.4 (OMe), 38.4
(CH2), 19.9 (SMe) ppm.
(SMe) ppm. IR (KBr): ν = 2921, 2852, 1585, 1475, 1235, 1071,
˜
780 cm–1.
Methyl 2-Acetylpent-4-enedithioate (3i): Red oil (141 mg, 75%
yield). 1H NMR (300 MHz, CDCl3): δ = 5.73–5.62 (m, 1 H, vinylic
CH), 5.13–4.99 (m, 3 H, tertiary CH, vinylic CH2), 4.35 (t, J =
7.2 Hz, 1 H, tertiary CH), 2.91–2.66 (m, 5 H, CH2 and SMe), 2.20
(s, 3 H, CH3) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 223.9
(C=S), 201.1 (C=O), 134.1, 117.5, 73.4, 37.0 (CH2), 27.9 (CH3),
20.1 (SMe) ppm.
Methyl 2-(4-Methylbenzoyl)pent-4-enedithioate (3c): Red oil
1
(221 mg, 84% yield). H NMR (300 MHz, CDCl3): δ = 7.94 (d, J
= 8.1 Hz, 2 H, Ar), 7.23 (d, J = 8.1 Hz, 2 H, Ar), 5.86–5.72 (m, 1
H, vinylic CH), 5.29 (t, J = 7.2 Hz, 1 H, tertiary CH), 5.13–5.00
(m, 2 H, vinylic CH2), 3.08–2.95 (m, 1 H, CH2), 2.88–2.65 (m, 1
H, CH2), 2.59 (s, 3 H, SMe), 2.38 (s, 3 H, tolyl CH3) ppm. 13C
NMR (75.5 MHz, CDCl3): δ = 232.0 (C=S), 193.0 (C=O), 144.3,
134.6, 133.6, 129.3, 129.0, 117.4, 67.7 (tertiary CH), 38.4 (CH2),
21.6 (tolyl CH3), 20.0 (SMe) ppm.
General Procedure for the Synthesis of α-Oxoketene-S,S-acetals 5a–
5e: To a solution of α-enolic dithioester 1 (1.0 mmol) in DMF
(5 mL) were added indium powder (1.2 mmol) and alkyl halide 2
(1.0 mmol), and the mixture was stirred at 60 °C for the stipulated
period of time. Upon completion, the reaction was treated with
dilute HCl solution followed by brine, and the resulting mixture
was extracted with ethyl acetate (2ϫ 10 mL). The combined or-
ganic layers were dried with anhydrous Na2SO4 and evaporated
under vacuum. The crude reaction mixture was purified by column
chromatography (increasing amounts of ethyl acetate in hexane) to
afford the pure α-oxoketene-S,S-acetals 5.
Methyl 2-Benzoyl-4-methylpent-4-enedithioate (3d): Red oil
1
(218 mg, 83% yield). H NMR (300 MHz, CDCl3): δ = 8.06 (d, J
= 7.5 Hz, 2 H, Ar), 7.55 (t, J = 7.2 Hz, 1 H, Ar), 7.47–7.42 (m, 2
H, Ar), 5.51 (t, J = 7.2 Hz, 1 H, tertiary CH), 4.73 (d, J = 19.2 Hz,
2 H, vinylic CH2), 3.09–3.02 (m, 1 H, CH2), 2.78–2.71 (m, 1 H,
CH2), 2.59 (s, 3 H, SMe), 1.78 (s, 3 H, CH3) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 232.1 (C=S), 193.4 (C=O), 141.9, 136.1,
133.3, 128.9, 128.6, 112.7, 66.2 (tertiary CH), 42.0 (CH2), 22.7
(CH3), 20.1 (SMe) ppm.
3-(Methylthio)-3-(propylthio)-1-(p-tolyl)prop-2-en-1-one (5a): Yel-
low solid (212 mg, 80% yield); m.p. 76–77 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.80 (d, J = 8.1 Hz, 2 H, Ar), 7.22 (d, J = 8.1 Hz, 2
H, Ar), 6.82 (s, 1 H, dithioacetal CH), 2.99 (t, J = 7.2 Hz, 2 H,
CH2 of SPr), 2.51 (s, 3 H, SMe), 2.39 (s, 3 H, tolyl CH3), 1.85–1.75
(m, 2 H, CH2 of SPr), 1.09 (t, J = 7.2 Hz, 3 H, CH3 of SPr) ppm.
13C NMR (75.5 MHz, CDCl3): δ = 185.4 (C=O), 164.8, 142.1,
136.6, 129.0, 127.7, 110.2, 36.0, 21.5, 20.9 (SMe), 15.2, 13.5 ppm.
Methyl 2-Benzoyl-3-methylpent-4-enedithioate (3e): Red oil
(210 mg, 80% yield, diastereomeric mixture). 1H NMR (300 MHz,
CDCl3): δ = 8.11–8.04 (m, 2 H, Ar), 7.56–7.43 (m, 3 H, Ar), 5.78–
5.66 (m, 1 H, vinylic CH), 5.31–5.22 (m, 1 H, CH), 5.12–4.92 (m,
2 H, vinylic CH2), 3.52–3.42 (m, 1 H, CH), 2.58 (d, J = 17.7 Hz, 3
H, SMe), 1.76 (q, J = 6.0 Hz, 3 H, CH3) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 230.4 (C=S), 193.4 (C=O), (140.3, 139.3),
(136.7, 136.7), (133.5, 133.3), (129.0, 129.0), (128.6, 128.6), (115.7,
115.3), (74.1, 74.0), (42.7, 41.8), (20.2, 20.0, SMe), (18.9, 17.1,
CH3) ppm.
IR (KBr): ν = 2969, 2932, 1602, 1477, 1180, 781 cm–1. HRMS:
˜
calcd. for 268.0872 [M + H]+; found 268.0935.
3-(Methylthio)-1-phenyl-3-(prop-2-yn-1-ylthio)prop-2-en-1-one (5b):
Yellow sticky solid (243 mg, 85% yield). 1H NMR (300 MHz,
CDCl3): δ = 7.82 (d, J = 8.1 Hz, 2 H, Ar), 7.38 (d, J = 8.1 Hz, 2
H, Ar), 6.73 (s, 1 H, dithioacetal CH), 3.11–3.01 (m, 4 H, 2 CH2 of
SEt), 1.45–1.34 (m, 6 H, 2 CH3 of SEt) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 184.1 (C=O), 165.7, 137.8, 137.6, 129.0, 128.6, 109.5,
28.3 (CH2 of SEt), 25.6 (CH2 of SEt), 13.7 (CH3 of SEt), 12.4 (CH3
of SEt) ppm.
Methyl 2-(4-Methoxybenzoyl)-3-methylpent-4-enedithioate (3f): Red
oil (229 mg, 78% yield, diastereomeric mixture). 1H NMR
(300 MHz, CDCl3): δ = 8.08–8.01 (m, 2 H, Ar), 6.91–6.86 (m, 2 H,
Ar), 5.76–5.64 (m, 1 H, vinylic CH), 5.24–5.16 (m, 1 H, CH), 5.08–
4.88 (m, 2 H, vinylic CH2), 3.81 (d, J = 2.7 Hz, 3 H, OMe), 3.44–
3.38 (m, 1 H, CH), 2.53 (d, J = 17.1 Hz, 3 H, SMe), 1.06–1.00 (m,
3 H, CH3) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 230.9 (C=S),
(191.6, 191.5, C=O), 163.7, (140.4, 139.3), (131.3, 131.3), 129.6,
(115.4, 115.1), (113.7, 113.7, 113.5, 113.4), (74.0, 73.9), (55.3, 55.3,
55.3, OMe), (42.5, 41.5), (20.0, 19.8, SMe), (18.7, 17.0, CH3) ppm.
MS: m/z (%) = 295 (10) [M + 1]+, 317 (55) [M + 23]+.
3-(But-3-en-1-ylthio)-3-(methylthio)-1-phenylprop-2-en-1-one (5c):
1
Yellow gel (218 mg, 83% yield, diastereomeric mixture). H NMR
(300 MHz, CDCl3): δ = 7.92–7.88 (m, 2 H, Ar), 7.48–7.40 (m, 3 H,
Ar), 6.79 (d, J = 25.2 Hz, 1 H, dithioacetal CH), 5.90–5.79 (m, 1
H, vinylic CH), 5.19–5.05 (m, 2 H, vinylic CH2), 3.14–3.05 (m, 2 H,
CH2), 2.54–2.46 (m, 5 H, CH2, SMe) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 185.4 (C=O), 165.0, 139.1, (135.7, 135.1), (132.1,
132.0, 131.6), 128.3, (127.6, 127.5), (117.1, 116.5), (110.2, 109.6),
(33.3, 32.9), (31.4, 30.4), (17.3, 15.1) ppm.
Methyl 2-(Thiophene-2-carbonyl)pent-4-enedithioate (3g): Red oil
1
(208 mg, 82% yield). H NMR (300 MHz, CDCl3): δ = 7.90 (d, J
= 3.6 Hz, 1 H, Ar), 7.66 (d, J = 4.5 Hz, 1 H, Ar), 7.11 (t, J =
3-(Ethylthio)-3-(methylthio)-1-(thiophen-2-yl)prop-2-en-1-one (5d):
4.5 Hz, 1 H, Ar), 5.82–5.73 (m, 1 H, vinylic CH), 5.18–5.01 (m, 3
Yellow sticky solid (213 mg, 87% yield, diastereomeric mixture).
H, tertiary CH, vinylic CH2), 3.06–2.99 (m, 1 H, CH2), 2.85–2.78 1H NMR (300 MHz, CDCl3): δ = 7.64–7.61 (m, 1 H, Ar), 7.52 (d,
Eur. J. Org. Chem. 2014, 2964–2971
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2969

M. S. Singh et al.
FULL PAPER
J = 4.8 Hz, 1 H, Ar), 7.09–7.06 (m, 1 H, Ar), 6.62 (d, J = 24.9 Hz,
1 H, dithioacetal CH), 3.10–2.99 (m, 2 H, CH2 of SEt), 2.53–2.49
(m, 3 H, SMe), 1.45–1.33 (m, 3 H, CH3 of SEt) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = (178.1, 177.9, C=O), (165.0, 164.9), (146.1,
146.1), (131.8, 131.7), (129.4, 129.4), 127.7, (109.7, 109.1), (28.1,
25.4), (17.1, 15.1), (13.6,12.3) ppm.
Ar), 5.66 (s, 1 H), 4.20 (q, J = 6.9 Hz, 2 H, CH2 of OEt), 1.57–
1.54 (m, 3 H, CH3 of OEt) ppm. 13C NMR (75.5 MHz, CDCl3): δ
= 165.5, 153.3, 132.2, 123.7, 123.0, 116.6, 115.7, 100.5, (90.3, 90.2),
65.1, 14.0 ppm.
Supporting Information (see footnote on the first page of this arti-
cle): Detailed experimental methods, optimization chart, NMR
1
study, crystal structures, copies of H and 13C NMR spectra, and
3-(Methylthio)-3-(propylthio)-1-(thiophen-2-yl)prop-2-en-1-one (5e):
Yellow viscous liquid (217 mg, 84% yield, diastereomeric mixture).
1H NMR (400 MHz, CDCl3): δ = 7.63 (br., 1 H, Ar), 7.54–7.52
(m, 1 H, Ar), 7.09 (br., 1 H, Ar), 6.64 (d, J = 26.4 Hz, 1 H, di-
thioacetal CH), 3.05–2.97 (m, 2 H, CH2 of SPr), 2.52 (d, J =
16.8 Hz, 3 H, SMe), 1.85–1.71 (m, 2 H, CH2 of SPr), 1.14–1.03 (m,
3 H, CH3 of SPr) ppm. 13C NMR (100 MHz, CDCl3): δ = 178.1
(C=O), 165.2, 146.1, 131.8, 129.4, 127.8, 109.7, 35.9, 20.8, 15.2,
13.6 ppm.
computational details.
Acknowledgments
The authors gratefully acknowledge the generous financial support
from the SERB, Department of Science and Technology (DST),
New Delhi (grant number SR/S1/Os66/2009), the Council of Scien-
tific and Industrial Research (CSIR), New Delhi [grant number
02(0072)/12/EMR-II], and the University Grant Commission
(UGC), New Delhi, UGC-UKIERI Partnership-2013, grant
number 184-16/2013(IC). S. C., T. C., and S. K. thank the UGC
and B. J. R thanks the CSIR for fellowships.
General Procedure for the Synthesis of 4-Alkoxy-2H-chromen-2-ones
7a–7e: To a solution of 4-hydroxycoumarin (6, 1.0 mmol) in DMF
(5 mL) were added indium powder (1.2 mmol) and alkyl/allyl hal-
ides 2 (1.0 mmol), and the mixture was stirred at 60 °C for the
stipulated period of time. Upon completion, the reaction was
treated with dilute HCl solution followed by brine, and the re-
sulting mixture was extracted with ethyl acetate (2ϫ 10 mL). The
combined organic layers were dried with anhydrous Na2SO4 and
evaporated under vacuum. The crude reaction mixture was purified
by column chromatography (increasing amounts of ethyl acetate in
hexane) to afford the pure 4-alkoxy-2H-chromen-2-ones 7.
[1] P. Knochel, Handbook of Functionalized Organometallics,
Wiley-VCH, Weinheim, Germany, 2005.
[2] For reviews on indium chemistry, see: a) Z.-L. Shen, S.-Y.
Wang, Y.-K. Chok, Y.-H. Xu, T.-P. Loh, Chem. Rev. 2013, 113,
271–401; b) J. S. Yadav, A. Antony, J. George, B. V.
Subba Reddy, Eur. J. Org. Chem. 2010, 591–605; c) U. K. Roy,
S. Roy, Chem. Rev. 2010, 110, 2472–2535; d) J. A. J. Pardoe,
A. J. Downs, Chem. Rev. 2007, 107, 2–45.
[3] a) A. N. Pae, Y. S. Cho, Curr. Org. Chem. 2002, 6, 715–737; b)
J. Podlech, T. C. Maier, Synthesis 2003, 633–655; c) V. Nair, S.
Ros, C. N. Jayan, B. S. Pillai, Tetrahedron 2004, 60, 1959–1982;
d) R. B. Kargbo, G. R. Cook, Curr. Org. Chem. 2007, 11, 1287–
1309; e) S. Araki, T. Shimizu, P. S. Johar, S.-J. Jin, Y. Butsugan,
J. Org. Chem. 1991, 56, 2538–2542; f) V. J. Bryan, T.-H. Chan,
Tetrahedron Lett. 1997, 38, 6493–6496; g) J. Yoo, K. E. Oh, G.
Keum, S. B. Kang, Y. Kim, Polyhedron 2000, 19, 549–551.
[4] a) L. C. Chao, R. D. Rieke, J. Org. Chem. 1975, 40, 2253–2255;
b) S. Araki, H. Ito, Y. Butsugan, Synth. Commun. 1988, 18,
453–458; c) S. Araki, Y. Butsugan, J. Chem. Soc., Chem. Com-
mun. 1989, 1286–1287; d) N. Fujiwara, Y. Yamamoto, J. Org.
Chem. 1999, 64, 4095–4101.
[5] a) Y.-H. Chen, M. Sun, P. Knochel, Angew. Chem. Int. Ed.
2009, 48, 2236–2239; Angew. Chem. 2009, 121, 2270; b) Y.-H.
Chen, P. Knochel, Angew. Chem. Int. Ed. 2008, 47, 7648–7651;
Angew. Chem. 2008, 120, 7760; c) Z.-L. Shen, Y.-C. Lai, C. H.
An Wong, K. K. K. Goh, Y.-S. Yang, H.-L. Cheong, T.-P. Loh,
Org. Lett. 2011, 13, 422–425; d) K. Takami, H. Yorimitsu, H.
Shinokubo, S. Matsubara, K. Oshima, Org. Lett. 2001, 3,
1997–1999; e) K. Lee, J. Lee, P. H. Lee, J. Org. Chem. 2002, 67,
8265–8268; f) J.-Y. Lee, P. Ho Lee, J. Org. Chem. 2008, 73,
7413–7416; g) P. Ho Lee, S.-Y. Sung, K. Lee, Org. Lett. 2001,
3, 3201–3204; h) D. Rodriguez, J. P. Sestelo, L. A. Sarandeses,
J. Org. Chem. 2004, 69, 8136–8139, and references cited therein.
[6] a) N. H. Werstiuk, Tetrahedron 1983, 39, 205–268; b) Z.-L.
Shen, K. K. K. Goh, H.-L. Cheong, C. H. An Wong, Y.-C. Lai,
Y.-S. Yang, T.-P. Loh, J. Am. Chem. Soc. 2010, 132, 15852–
15855; c) P. H. Lee, Y. Park, S. Park, E. Lee, S. Kim, J. Org.
Chem. 2011, 76, 760–765; d) J. Mo, D. Eom, S. H. Kim, P. H.
Lee, Chem. Lett. 2011, 40, 980–982.
4-(Allyloxy)-2H-chromen-2-one (7a): White solid (179 mg, 88%
yield); m.p. 114–115 °C. 1H NMR (300 MHz, CDCl3): δ = 7.84 (d,
J = 7.8 Hz, 1 H, Ar), 7.54 (t, J = 7.8 Hz, 1 H, Ar), 7.32–7.24 (m,
2 H, Ar), 6.13–6.04 (m, 1 H, vinylic CH), 5.69 (s, 1 H), 5.53–5.40
(m, 2 H, vinylic CH2), 4.69 (d, J = 5.4 Hz, 2 H, CH2) ppm. 13C
NMR (75.5 MHz, CDCl3): δ = 165.1, 162.7, 153.3, 132.3, 130.6,
123.8, 123.0, 119.5, 116.7, 115.6, 90.9, 69.7 ppm. IR (KBr): ν =
˜
3082, 1720, 1399, 1247, 940, 844, 768 cm–1. HRMS: calcd. for
203.0703 [M + H]+; found 203.0702.
4-[(2-Methylallyl)oxy]-2H-chromen-2-one (7b): White sticky solid
1
(182 mg, 85% yield). H NMR (300 MHz, CDCl3): δ = 7.84 (d, J
= 7.8 Hz, 1 H, Ar), 7.54 (t, J = 7.8 Hz, 1 H, Ar), 7.32–7.25 (m, 2
H, Ar), 5.68 (s, 1 H), 5.13 (d, J = 17.1 Hz, 2 H, vinylic CH2), 4.59
(s, 2 H, CH2) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 165.1, 162.8,
153.3, 138.4, 132.3, 123.8, 122.9, 116.7, 115.7, 114.5, 90.9, 72.6,
19.3 ppm.
4-Propoxy-2H-chromen-2-one (7c): White solid (168 mg, 82%
yield); m.p. 110–111 °C. 1H NMR (300 MHz, CDCl3): δ = 7.83 (d,
J = 7.5 Hz, 1 H, Ar), 7.54 (t, J = 7.5 Hz, 1 H, Ar), 7.32–7.24 (m,
2 H, Ar), 5.66 (s, 1 H), 4.09 (t, J = 6.3 Hz, 2 H, CH2 of OPr), 1.97–
1.88 (m, 2 H, CH2 of OPr), 1.11 (t, J = 7.2 Hz, 3 H, CH3 of
OPr) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 165.6, 162.9, 153.3,
132.2, 123.7, 122.9, 116.7, 115.8, 90.3, 70.7, 21.9, 10.4 ppm. IR
(KBr): ν = 2967, 2881, 1708, 1624, 1240, 928, 781 cm–1.
˜
4-(But-3-en-1-yloxy)-2H-chromen-2-one (7d): Highly viscous liquid
1
(177 mg, 82% yield). H NMR (300 MHz, CDCl3): δ = 7.80 (d, J
= 4.8 Hz, 1 H, Ar), 7.54 (t, J = 7.2 Hz, 1 H, Ar), 7.31–7.24 (m, 2
H, Ar), 5.95–5.86 (m, 1 H, vinylic CH), 5.67 (s, 1 H), 5.26–5.16 (m,
2 H, vinylic CH2), 4.17 (t, J = 6.6 Hz, 2 H, CH2), 2.70–2.66 (m, 2
H, CH2) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 165.4, 162.9,
153.1, 133.2, 132.2, 123.8, 122.8, 118.0, 116.6, 115.6, 90.3, 68.2,
32.7 ppm.
[7] B. C. Ranu, S. Banerjee, L. Adak, Tetrahedron Lett. 2007, 48,
7374–7379.
[8] a) I. Garcia-Orozco, M. C. Ortega-Alfaro, J. G. Lopez-Cortes,
R. A. Toscano, C. Alvarez-Toledano, Inorg. Chem. 2006, 45,
1766–1773; b) M. S. Singh, G. C. Nandi, T. Chanda, RSC Adv.
2013, 3, 14183–14198; c) S. Chowdhury, T. Chanda, S. Koley,
B. J. Ramulu, R. C. F. Jones, M. S. Singh, Org. Lett. 2013, 15,
5386–5389.
4-Ethoxy-2H-chromen-2-one (7e): White solid (161 mg, 85% yield);
m.p. 106–107 °C. 1H NMR (300 MHz, CDCl3): δ = 7.82 (d, J =
7.8 Hz, 1 H, Ar), 7.53 (t, J = 7.5 Hz, 1 H, Ar), 7.32–7.23 (m, 2 H,
2970
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 2964–2971

Indium(0)-Mediated Csp3–S/O Cross-Coupling Approach
[9] a) S. Chowdhury, T. Chanda, G. C. Nandi, S. Koley, B. J. Ra-
mulu, S. K. Pandey, M. S. Singh, Tetrahedron 2013, 69, 8899–
8903; b) S. Masson, A. Thuillier, Tetrahedron Lett. 1982, 23,
4087–4090.
[10] For different proposed structures of organoindium complexes,
see: a) M. J. S. Gynane, I. J. Worrall, J. Organomet. Chem.
1974, 81, 329–334, and references cited therein; b) S. Araki, H.
Ito, Y. Butsugan, J. Org. Chem. 1988, 53, 1831–1833; c) T. H.
Chan, Y. Yang, J. Am. Chem. Soc. 1999, 121, 3228–3229, and
references cited therein; d) M. Yasuda, M. Haga, Y. Nagaoka,
A. Baba, Eur. J. Org. Chem. 2010, 5359–5363.
[13]
a) J. G. Deshmukh, M. H. Jagdale, R. B. Mane, M. M. Salun-
khe, J. Indian Chem. Soc. 1986, 63, 442–443; b) A. A. Avetis-
yan, A. G. Alvandzhyan, Russ. J. Org. Chem. 2006, 42, 1063–
1067; c) K. C. Majumdar, A. Biswas, P. P. Mukhopadhyay, Can.
J. Chem. 2005, 83, 2046–2051; d) A. Patra, A. K. Mukho-
padhyay, A. K. Mitra, Indian J. Chem. Sect. B 1986, 25, 1167–
1170, and references cited therein.
a) A. Srivastava, V. Mishra, P. Singh, R. Kumar, J. Appl. Polym.
Sci. 2012, 126, 395–407; b) C. Supuran, S. Dedhar, F. Carta,
J.-Y. Winum, P. C. McDonald, PCT Int. Patent Appl.
2012070024, 2012; c) F. Carta, A. Maresca, A. Scozzafava,
C. T. Supuran, Bioorg. Med. Chem. 2012, 20, 2266–2273.
[14]
[15]
[11] S. Apparao, S. S. Bhattacharjee, H. Ila, H. Junjappa, J. Chem.
Soc. Perkin Trans. 1 1985, 641–645, and references cited
therein.
a) V. P. Reddy, K. Swapna, A. V. Kumar, K. Rama Rao, J. Org.
Chem. 2009, 74, 3189–3191; b) V. P. Reddy, A. V. Kumar, K.
Swapna, K. Rama Rao, Org. Lett. 2009, 11, 1697–1700.
[12] a) CCDC-894933 (for 1b) and -908493 (for 5a) contain the sup-
plementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif;
b) CCDC-938934 (for 7c) contains the supplementary crystal-
lographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
[16] T. H. Chan, C. J. Li, M. C. Lee, Z. Y. Wei, Can. J. Chem. 1994,
72, 1181–1192, and references cited therein.
[17] R. Samuel, C. V. Asokan, S. Suma, P. Chandran, S. Retnamma,
E. R. Anabha, Tetrahedron Lett. 2007, 48, 8376.
Received: December 1, 2013
Published Online: March 27, 2014
Eur. J. Org. Chem. 2014, 2964–2971
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2971