Direct Synthesis of γ-Keto Sulfones from Allylic Alcohols: One-Pot Palladium(II)-Catalyzed Generation of Enones Followed by Water-Mediated 1,4-Addition of Organosulfinates

Article abstract of DOI:10.1002/ejoc.201600494

Allylic alcohols were exploited as synthetic precursors of γ-keto sulfones. The reaction involved the one-pot generation of α,β-enones in situ from the allylic alcohols by using a Pd^II–dioxygen catalytic system and subsequent sulfa-Michael addition in the presence of water. Importantly, water was identified as a sustainable substitute for a toxic copper salt to promote organosulfonyl addition. Diverse examples of aromatic and aliphatic γ-keto sulfones were prepared. Specially, Ar–X (X = Br, Cl) bonds were tolerated, which indicated a chemoselective catalytic system for the preparation of halogen-bearing γ-keto sulfones. This one-pot method does not require an acid, a base, or isolation of any intermediate. Control experiments indicated that the active catalyst of the first step also promoted the subsequent C–S bond-formation reaction. Water was found to accelerate the reaction rate and to be involved in the protonolysis of the σ-alkylpalladium complex, as corroborated by deuterium incorporation.

Full text of DOI:10.1002/ejoc.201600494

DOI: 10.1002/ejoc.201600494
Full Paper
γ-Keto Sulfones
Direct Synthesis of γ-Keto Sulfones from Allylic Alcohols: One-
Pot Palladium(II)-Catalyzed Generation of Enones Followed by
Water-Mediated 1,4-Addition of Organosulfinates
Mari Vellakkaran,[a] Murugaiah M. S. Andappan,[b] Kommu Nagaiah,*[a] and
Jagadeesh Babu Nanubolu[c]
Abstract: Allylic alcohols were exploited as synthetic precur- catalytic system for the preparation of halogen-bearing γ-keto
sors of γ-keto sulfones. The reaction involved the one-pot gen-
eration of α,ꢀ-enones in situ from the allylic alcohols by using
a PdII–dioxygen catalytic system and subsequent sulfa-Michael
addition in the presence of water. Importantly, water was identi-
fied as a sustainable substitute for a toxic copper salt to pro-
mote organosulfonyl addition. Diverse examples of aromatic
and aliphatic γ-keto sulfones were prepared. Specially, Ar–X (X =
Br, Cl) bonds were tolerated, which indicated a chemoselective
sulfones. This one-pot method does not require an acid, a base,
or isolation of any intermediate. Control experiments indicated
that the active catalyst of the first step also promoted the sub-
sequent C–S bond-formation reaction. Water was found to ac-
celerate the reaction rate and to be involved in the protonolysis
of the σ-alkylpalladium complex, as corroborated by deuterium
incorporation.
Introduction
pharmaceuticals,[3] agrochemicals,[4] and advanced organic ma-
terials.[5] The 1,4-addition of sulfur nucleophiles to α,ꢀ-unsatu-
rated carbonyl compounds or related derivatives (also known
as the sulfa-Michael reaction) is a vital tool for the formation of
C–S bonds.[6] The development of new synthetic methodolo-
gies to generate sulfur-bearing organic compounds will defi-
nitely create value owing to the far-reaching and wide presence
of sulfur-containing compounds in materials science, marketed
drugs, and agrochemicals. The sulfa-Michael reaction can be
performed in a catalytic fashion by exploiting either transition
metals or organocatalysts to promote the reaction.[7] Sulfones
are also known for their synthetic versatility as flexible interme-
diates in organic synthesis[8] in well-known organic transforma-
tions such as the Ramberg–Bäcklund reaction[9] and Julia olefin-
ation.[10] The sulfone motif can facilitate potential target–ligand
interactions through its two H-bond acceptors and can also
modulate physicochemical properties if incorporated into a
drug molecule. Sulfone-containing compounds possess a wide
range of biological properties (Figure 1),[11] which include anti-
fungal, antibacterial, and antitumor activities,[12,13] and they are
known to inhibit several enzymes such as cyclooxygenase-2
(COX-2),[14,15] HIV-1 reverse transcriptase,[16,17]integrin VLA-4,[18]
and ATPase.[19]
In recent years, PdII catalysis has earned prominent use in C–C
bond-formation reactions for the synthesis of pharmaceuticals,
agrochemicals, and natural products.[1] PdII catalysis has found
well-known applicability in the oxidation of alcohols, Wacker
oxidation, Saegusa oxidation, oxidative Heck reaction [e.g., C–C
bond formation], C–H functionalization, and so on.[2] The sus-
tainability of the catalyst in these transformations is achieved
by oxidation of the Pd0 species into a PdII species by using a
terminal oxidant (e.g., molecular oxygen and transition-metal
oxidants). Molecular oxygen is undoubtedly the preferred
choice, because of its many ecofriendly advantages, including
its nontoxicity, abundant availability from nature, and the fact
that it does not leave behind any solid waste or promote any
side reaction. By contrast, metal oxidants are known to promote
undesirable side reactions. Hence, the employment of dioxygen
as a green oxidant in metal-catalyzed [e.g., PdII] organic trans-
formations would constitute an environmentally conscious
strategy.
Sulfones are attractive as a structural motif and as synthetic
precursors of several types of organic compounds, including
[a] Organic and Biomolecular Chemistry Division, CSIR – Indian Institute of
Chemical Technology,
Traditionally, γ-keto sulfones are synthesized by Michael-type
addition of α,ꢀ-enones with thiols to form the corresponding
thio-substituted γ-ketones. Further, the thio-substituted γ-ket-
ones are oxidized by peroxides or other oxidants to form the
corresponding γ-keto sulfones.[20,21] Alternatively, the γ-keto
sulfone derivatives can be prepared by the intermolecular
Stetter reaction of aldehydes with α,ꢀ-unsaturated sulfones in
the presence of an N-heterocyclic carbene (NHC) catalyst
(Scheme 1, a)[22] and by coupling α,ꢀ-unsaturated ketones with
Tarnaka, Hyderabad 500007, India
E-mail: nagaiah@iict.res.in
http://iictindia.org/
[b] Syngene,
Biocon Park, Bengaluru 560009, India
E-mail: murugaiah.andappan@gmail.com
[c] Lab of X-ray Crystallography, CSIR-Indian Institute of Chemical Technology,
Hyderabad 500 007, India
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201600494.
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(A1) and sodium 4-methylbenzenesulfinate (S1) as the model
substrates by using the conditions [palladium(II) source, base,
oxidant, and additive] known to be conducive to alcohol oxid-
ation.[24,25] Disappointingly, neither the keto intermediate nor
the final product (γ-keto sulfone) was observed (Table 1, en-
tries 1 and 2). However, we were delighted to detect the forma-
tion of the γ-keto sulfone by switching from polar, aprotic DMF
to less-polar toluene or 1,4-dioxane in the presence or absence
of triethylamine and a copper(II) salt, though the yield was low
(Table 1, entries 3–6). In addition to the product of interest, we
observed varying amounts of a desulfitative arylation product
(dihydrochalcone) as the byproduct, which unproductively con-
tributed to the low yield of the γ-keto sulfone.
Figure 1. Examples of pharmaceutically relevant sulfones.
arenesulfinate salts in the presence of a Lewis acid or base
(Scheme 1, b).[23] However, some of these procedures require
multiple steps to synthesize the sulfones and suffer from harsh
reaction conditions with the formation of undesirable byprod-
ucts. Therefore, there is still a demand for the development of
more sustainable and green methods for the synthesis of γ-
keto sulfones.
Table 1. Optimization protocol: sequential allylic alcohol oxidation and 1,4-
sulfonyl addition.[a]
Entry
Base
Solvent
Additive
Yield[b] [%]
1[c]
2[c]
3[c]
4[c]
5[c]
6[c]
7
–
–
Et3N
Et3N
–
–
Et3N
Et3N
–
–
–
Et3N
–
–
–
–
–
DMF
DMF
–
0
0
Cu(OAc)2·H2O
–
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
–
toluene
toluene
toluene
dioxane
dioxane
toluene
dioxane
toluene
toluene
DMSO
DMF
18
26
31
28
28
26
79
90
92
0
Scheme 1. (a,b) Synthesis of γ-keto sulfones from aldehydes or enones by
Lewis acid or base catalyzed reactions; (c) palladium-catalyzed synthesis of
γ-keto sulfones directly from allylic alcohols (the precursor of enones) and
organosulfinates.
8
9
–
Cu(OAc)2·H2O
Cu(OAc)2·H2O
H2O (0.5 mL)
H2O (0.5 mL)
H2O (0.5 mL)
H2O (0.5 mL)
H2O (0.5 mL)
H2O (0.5 mL)
H2O (0.5 mL)
10
11
12
13
14
15
16
17
0
0
0
0
DMA
Results and Discussion
2-MeTHF
MeOH
EtOAc
We report herein a practical and sustainable route to γ-keto
sulfones through the PdII-catalyzed oxidation of alcohols fol-
lowed by 1,4-sulfonyl addition with organosulfinates by using
oxygen as the terminal oxidant in the first step and water as a
promoter of the Michael addition of the organosulfinate to the
resultant enone in the second step. This one-pot method does
not require the use of any external Lewis acid or Lewis base
and, importantly, does not require isolation of the intermediate
enone. Incorporation of water as a co-solvent or Michael-addi-
tion promoter in addition to the utility of oxygen as an eco-
friendly oxidant significantly enhance the green aspects of
methodology (Scheme 1, c). Besides, a strategy based on sulf-
inate addition would benefit from substrate-type expansion,
which is one of the goals of the present research.
0
[a] Until otherwise indicated, the reaction was performed with 1-(4-methoxy-
phenyl)prop-2-en-1-ol (A1, 1.0 mmol), Pd(OAc)2 (0.1 equiv.), and base
(0.12 equiv.) under an atmosphere of oxygen (balloon) at 90 °C in solvent
(3.0 mL) for 6.0 h. After adding sodium 4-methylbenzenesulfinate (S1,
1.2 mmol) and the additive {Cu(OAc)2·H2O (0.5 equiv.) or H2O (0.5 mL)}, the
reaction was continued for 15.0 h. [b] Yield of isolated product (average of
two runs). [c] The reaction was performed with A1 (1.0 mmol), S1 (1.2 mmol),
Pd(OAc)2 (0.1 equiv.), base (0.12 equiv.), and additive (0.5 equiv.) under an
atmosphere of oxygen (balloon) at 90 °C in solvent (3.0 mL) for 18.0 h.
The unexpected formation of the byproduct forced us to in-
vestigate whether we could selectively achieve the desired pal-
ladium(II)-mediated oxidative sulfonylation of allylic alcohols
(Scheme 1, c) by suppressing the concurrent palladium(II)-cata-
To identify suitable conditions for the PdII-involved oxid- lyzed oxidative Heck-type pathway for the oxidative isomeriza-
ation/sulfonyl addition to generate γ-keto sulfones from allylic tion of the allylic alcohols to yield the unwanted dihydrochalco-
alcohols, we began with 1-(4-methoxyphenyl)prop-2-en-1-ol nes (Scheme 2, c). The oxidative Heck-type catalytic cycle is
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supposed to proceed through the generation of an arylpalla- 2-MeTHF, methanol, and ethyl acetate were met with little suc-
dium(II) species by desulfitative aryl addition of an arenesulf- cess, as these solvents were found to be counterproductive to
inate to palladium(II) in a transmetalation fashion, with subse- the generation of the unsaturated ketone in situ by the oxid-
quent incorporation of the allylic alcohol into the arylpalla- ation of the allylic alcohol in the first step (Table 1, entries 15–
dium(II) intermediate through olefinic π-bond conjugation, sub- 17).
sequent aryl migration, and finally hydrogen-transfer isomeriza-
tion to afford the ꢀ-arylethyl ketone. Hence, we devised a troub-
leshooting strategy to oxidize the alcohol first to generate the
corresponding enone in situ followed by subsequent introduc-
tion of the sodium arenesulfinate in the same pot to eliminate
arylpalladium(II) insertion into the allylic C=C bond. Disappoint-
ingly, we did not observe any improvement in the yield of the
desired γ-keto sulfone upon exploiting this strategy (with 1,4-
dioxane or toluene as solvent and oxygen as the oxidant) and
there was no suppression in the formation of the desulfitative
arylation product (Table 1, entries 7 and 8). The formation of
the ꢀ-arylethyl ketone byproduct (in spite of our attempts to
eliminate the presence of the allylic alcohol by converting it
into the corresponding enone by oxidation) suggested to us
the prevalence of a third palladium(II)-mediated pathway
(Scheme 2, a). This pathway appeared to involve the addition
of arylpalladium(II) on the enone olefin and subsequent proto-
nolysis of the σ-alkylpalladium(II) complex. Gratifyingly, signifi-
cant improvement in the yield was noted upon restoring the
use of the copper(II) salt as a Lewis acid additive (Table 1, en-
try 9). Changing the solvent from 1,4-dioxane to toluene helped
to improve the yield further (Table 1, entry 10). Considering the
toxic nature of the waste-generating copper salt, we looked
for an environmentally sustainable alternative. To our surprise,
replacement of the copper salt with water (H2O) as a green
additive resulted in the highest yield (Table 1, entry 11).
Armed with efficient conditions (Table 1, entry 10), we next
investigated the influence of electronic and steric factors on the
scope of the preparative outcome by coupling diverse sodium
organosulfinates and allylic alcohols. Electron-neutral (un-
substituted) benzenesulfinate gave an excellent yield, similar to
that obtained with electron-rich 4-methylbenzenesulfinate
(Scheme 3, compounds 1 and 2). Importantly, halogen-bearing
(–Cl and –Br) sodium arenesulfinates gave desired products 3
and 4 chemoselectively without the concurrent formation of
byproducts, which resulted from oxidative addition of Pd0 to
the Ar–X bond [e.g., Pd0-mediated Heck-type coupling between
the aryl halide and allylic alcohol to afford the ꢀ-arylalkyl ket-
one, Heck coupling of the aryl halide and the oxidative interme-
diate (α,ꢀ-enone), Suzuki-type aryl–aryl bond formation by cou-
pling of the aryl halide with the arenesulfinate after sulfur diox-
ide extrusion, and coupling of the aryl halide with the aryl sulfi-
nate to afford the biaryl sulfone (without sulfur extrusion) and
dehalogenation reaction]. This chemoselectivity provides an op-
portunity for organic and medicinal chemists to preserve the
halogen handles, which can be utilized for transition-metal-cat-
alyzed C–C, C–N, and C–O bond-forming diversification such as
Heck, Suzuki, Sonogashira, Buchwald, and Ullmann-type cou-
pling to deliver pharmaceutically important compounds. So-
dium methanesulfinate, an example of an aliphatic sulfinate,
underwent the coupling efficiently to afford corresponding sulf-
one 5. This suggested that electronically different aryl and alkyl
sulfinates could undergo the 1,4-addition with equal efficiency.
Scheme 2. Scope of chemoselectivity: PdII-mediated oxidative C–S or C–C
bond formation by coupling of allylic alcohols and organosulfinate salts
through three different catalytic pathways.
Solvent screening led to the identification of toluene as the
most productive solvent. The formation of the product was not
observed in the presence of polar aprotic solvents such as
DMSO, DMF, and dimethylacetamide (DMA) (Table 1, entries 12–
14), which indicated that these solvents were completely un-
Scheme 3. Preparative scope of γ-keto sulfones on coupling differently substi-
tuted organosulfinate salts.
Next, we investigated the scope and limitations of different
suited for this transformation. Our attempts to replace toluene types of allylic alcohols (Schemes 4 and 5) and the influence of
in the first step with solvents of higher green character such as the electronic and steric factors by coupling sodium 4-methyl-
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benzenesulfinate with diverse allylic alcohols. Eleven different product 15 in good yield. In most cases, the products were
1-arylpropenols with differently activated aryl ring systems un- isolated as crystalline solids, which prompted us to determine
derwent productive coupling to afford the corresponding prod- the crystal structure. As an example, the structure of compound
ucts (Scheme 4) in good yields. No difference in preparative 7, elucidated from single-crystal X-ray diffraction, is depicted in
outcome was observed between 1-arylpropenols with electron- Figure 2. The 1-arylpropenols underwent efficient coupling with
rich aryl systems (containing alkyl and –OMe substitutions), methanesulfinate salt 16, which suggested the lack of any dis-
electron-poor aryl systems (containing cyano and bromo substi- parity between the aromatic and aliphatic sulfinates on the pre-
tutions), and fused aromatics. Our next endeavor was to investi- parative outcome.
gate the chemoselectivity upon coupling of halogen-substi-
tuted 1-arylpropenol, as aryl–halogen bonds are known to be
highly susceptible to Pd0-mediated oxidative addition. The
bromo-substituted allylic alcohol reacted chemoselectively
(without the concomitant formation of byproducts resulting
from Pd0-catalyzed coupling) to give desired product 12 in
good yield. Thus, the ability to perform the PdII-directed cou-
pling to deliver halogen-installed products was confirmed; no-
table, this is beyond the synthetic scope of Pd0-mediated cou-
pling. Both differently fused 1-(1-naphthyl)propanol and 1-(1-
pyrene)propanol furnished coupling products 13 and 14 in
good yields, which indicated the broad applicability of the
method. Nevertheless, 1-(1-styrene)propenol underwent regios-
elective 1,4-sulfonyl addition on the terminal olefin to afford
Scheme 5. Preparative scope of γ-keto sulfones on coupling 1-alkyl- and 1-
alkenyl-substituted propenols.
Figure 2. ORTEP diagram of compound 7.
We next investigated the reactivity of allylic alcohols by re-
placing the 1-aryl substitution with a 1-alkyl substitution. The
propenols bearing linear chains underwent efficient coupling
to give the corresponding products (Scheme 5, see compounds
17–19). Branched allylic alcohols furnished coupling products
20 and 21 in good yields. Our transformation was found to be
highly regioselective with the occurrence of arylation at only
the terminal olefin and not at the internal olefin, as demon-
strated in the case of compounds 20 and 21 bearing both inter-
Scheme 4. Preparative scope of γ-keto sulfones on coupling differently substi-
tuted 1-arylprop-2-en-1-ol derivatives.
nal and terminal olefins. Between electron-rich and electron-
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deficient terminal olefins, the sulfa-Michael addition occurred was investigated in the presence of Pd2(dba)3 (dba = dibenzyl-
exclusively at the activated enone olefin (see compound 21).
Disappointingly, no desired oxidative 1,4-sulfonyl addition
product was observed with simple allyl alcohol upon treatment
with 4-methylbenzenesulfinate. However, this result was not
surprising, as the in situ oxidation product (acrolein) is known
to be unstable at elevated temperatures with ready tendency
to undergo rapid polymerization.
ideneacetone) as a source of Pd0 active species under oxygen-
excluded condition (reaction d, Scheme 6). In this case, no de-
sired product was evident. The above results suggest that only
palladium in its lower oxidation state (+2) was capable of pro-
moting C–S bond formation. A significant amount of the start-
ing material was recovered upon excluding water under the
standard conditions (reaction e, Scheme 6). A drastic decelera-
tion in the reaction rate was indicative of the necessity for water
for C–S bond formation and the participation of water in the
catalytic cycle. To understand the possible role of water in the
facilitation of the productive coupling, water was replaced with
D2O (0.5 mL) in the reaction system.
This resulted in the exclusive formation of deuterium-in-
stalled 1-(4-methoxyphenyl)-3-tosyl-2(2H1)propan-1-one (1-d1)
(Scheme 7), whereas normal product 1 was not obtained. Incor-
poration of deuterium at the carbon atom α to the ketone is
likely an indication of proteolysis in the final step of the cataly-
sis to release the parent and active catalyst. Beyond protonoly-
sis, water can also influence the reaction outcome as a solvent
and as a ligand to the PdII species. The sodium arene/alkanesul-
finate is expected to have poor solubility in toluene (solvent in
the first step), which contributes to the very low rate of conver-
sion. However, it is readily soluble in water, and the resultant
aqueous solution is expected to blend well at elevated temper-
atures in the biphasic medium with the feasibility of improved
conversion. Finally, the role of water as a ligand to stabilize the
palladium complex cannot be ruled out.
To investigate a plausible mechanistic pathway for the sec-
ond step of the reaction, we conducted several control experi-
ments by isolating pure vinyl ketone A1a and then subjecting
it to coupling with S1. As expected, desired product 1 was iso-
lated in good yield under the standard conditions (reaction a,
Scheme 6). This confirmed the involvement of the enone, which
was generated in situ in the catalytic cycle. In a second experi-
ment, vinyl ketone A1a and S1 were subjected to the standard
conditions without the addition of Pd(OAc)2 (reaction b,
Scheme 6). However, no product formation was observed,
which implied that the presence of a palladium(II) species was
critical to promote the coupling of the enone and arenesulf-
inate. In a third experiment (reaction c, Scheme 6), successful
coupling was evident, even in the absence of an oxidant (oxy-
gen-free inert atmosphere), which implied that the oxidant did
not play a role in the coupling reaction. From this result it can
be interpreted that the active palladium(II) species is regener-
ated at the end of the catalytic cycle, and thereby an oxidant is
not required. This is in sharp contrast to classical PdII-mediated
catalysis [e.g., vinylation of arylpalladium(II)], which generates
Pd0 after reductive elimination and, hence, requires a terminal
oxidant to regenerate the active catalyst. Sulfa-Michael addition
Scheme 7. Observation of deuterium installation upon sulfa-Michael addition
of the α,ꢀ-enone intermediate in the presence of deuterium oxide.
On the basis of inferences from the control experiments, a
plausible mechanism is depicted in Figure 3. The first step,
which involves oxidation of the allylic alcohol to the enone,
begins with coordination of the alcohol to LnPdIIX2 (X = OAc)
to form complex B, which subsequently undergoes deprotona-
tion to afford Pd–alkoxide complex C. Subsequent ꢀ-hydride
elimination leads to enone C and PdII-H D. Then, D decomposes
into Pd0 species E, which is oxidized by O2 and HX; this regener-
ates the active PdII catalyst.[26] The second step, which involves
oxidative sulfonylation of the enone, begins with regenerated
PdIIX2 complex A (obtained from oxidation of the Pd0 species
by O2). The addition of the organosulfinate to the active catalyst
from the catalytic cycle of the first step results in the formation
of organosulfonyl–PdII species F, which subsequently undergoes
insertion into the enone olefinic bond followed by the migra-
tion of organosulfonyl group from the metal center to the ole-
Scheme 6. Investigation of the feasibility of sulfa-Michael addition with the
isolated enone (oxidation product) under controlled conditions: (a) coupling
under the standard conditions; (b) 1,4-arylsulfonyl addition in the absence of
Pd(OAc)2; (c) 1,4-arylsulfonyl addition in the absence of the oxidant (under
an inert atmosphere); (d) 1,4-arylsulfonyl addition in the presence of
Pd2(dba)3 as a source of Pd0; (e) 1,4-arylsulfonyl addition in the absence of
water as a co-solvent.
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shifts are expressed in ppm. HRMS (ESI) spectroscopic data were
collected by using a Q-star & ORBITRAP high-resolution mass spec-
trometer.
finic bond of the enone. Resultant oxypalladium complex G is
expected to be in tautomerization with carbopalladium com-
plex H. PdII–alkyl complex H undergoes protonolysis in the
presence of water to liberate γ-keto sulfone III and the active
LnPdII(A) catalyst to start a new catalytic cycle. As discussed
earlier, protonolysis of the α-ketocarbopalladium complex is
corroborated by insertion of the deuterium atom in the pres-
ence of D2O (Scheme 7). This event could partly explain the
acceleration of the reaction rate by water.
General Procedure for the Synthesis of γ-Keto Sulfones from
Allylic Alcohols: A 10.0 mL round-bottomed flask with an attached
oxygen balloon (1 atm) was charged with a solution of the allylic
alcohol (1.0 mmol) and Pd(OAc)2 (0.022 g, 0.1 mmol) in toluene
(3.0 mL). The mixture was vigorously stirred at 90 °C for 6 h. The
flask was then opened. After adding the sodium aryl/alkyl sulfinate
(1.2 mmol) and H2O (0.5 mL) to the mixture, stirring was continued
for 15 h at 90 °C in the opened flask. After cooling to room tempera-
ture, the mixture was partitioned between EtOAc (25.0 mL) and
water (25.0 mL) in a separatory funnel. The organic layer was
washed with water and brine, dried with anhydrous Na2SO4 (s), and
concentrated in vacuo. The residue was purified by column chroma-
tography to afford the pure product.
1-(4-Methoxyphenyl)-3-tosylpropan-1-one (1): Following the
general procedure, the residue was purified by column chromatog-
raphy (silica gel 100–200 mesh, 15 % EtOAc/hexane) to afford the
1
title product as a colorless solid (0.292 g, 92 %), m.p. 99–100 °C. H
NMR (500 MHz, CDCl3) δ 7.88 (d, J = 8.9 Hz, 2 H), 7.81 (d, J = 8.3 Hz,
2 H), 7.35 (d, J = 8.0 Hz, 2 H), 6.91 (d, J = 8.9 Hz, 2 H), 3.85 (s, 3 H),
3.52 (t, J = 8.4 Hz, 2 H), 3.40 (t, J = 8.4 Hz, 2 H), 2.43 ppm (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 193.9, 164.0, 144.9, 136.1, 130.4, 130.0,
128.9, 128.0, 113.9, 55.5, 51.2, 31.1, 21.6 ppm. (IR, neat): ν = 3020,
˜
1690, 1317, 1214, 743 cm–1. HRMS (ESI): calcd. for [C17H18O4SNa]+
341.08180; found 341.08125.
Figure 3. Plausible mechanism for the PdII-catalyzed oxidation of allylic alco-
hols and subsequent 1,4-organosulfonyl addition with the regenerated PdII
catalyst of step I.
1-(4-Methoxyphenyl)-3-(phenylsulfonyl)propan-1-one
(2):[27]
Following the general procedure, the residue was purified by col-
umn chromatography (silica gel 100–200 mesh, 15 % EtOAc/hex-
ane) to afford the title product as a colorless solid (0.270 g, 89 %),
m.p. 101–102 °C. 1H NMR (500 MHz, CDCl3): δ = 7.96 (dd, J = 8.4,
1.2 Hz, 2 H), 7.91 (d, J = 8.9 Hz, 2 H), 7.67 (t, J = 7.5 Hz, 1 H), 7.58
Conclusions
In conclusion, we demonstrated for the first time a practical (t, J = 7.7 Hz, 2 H), 6.94 (d, J = 8.9 Hz, 2 H), 3.88 (s, 3 H), 3.57–3.53
(m, 2 H), 3.47–3.43 ppm (m, 2 H). 13C NMR (75 MHz, CDCl3): δ =
and sustainable route to γ-keto sulfones directly from enone
193.9, 164.0, 139.1, 134.0, 130.4, 129.4, 128.9, 128.0, 114.0, 55.6, 51.2,
precursors (i.e., allylic alcohols). This new method is based on a
green approach and involves the use of oxygen as the reoxidant
in the palladium(II)-mediated oxidation of propenols in the first
step with successful replacement of the toxic copper salt with
water without any compromise in yield. This one-pot method
does not require the use of an acid, a base, or the isolation of
any intermediate. Halogen-bearing γ-keto sulfones were syn-
thesized in good yields. Investigation into the mechanism by
performing the reaction with D2O indicated insertion of a deu-
terium atom on the α-carbon atom to the ketone.
30.9 ppm. (IR, neat): ν = 3020, 1671, 1312, 1414, 1214, 712 cm–1
.
˜
HRMS (ESI): calcd. for [C16H17O4S]+ 305.08421; found 305.08360.
3-[(4-Bromophenyl)sulfonyl]-1-(4-methoxyphenyl)propan-1-
one (3):[24] Following the general procedure, the residue was puri-
fied by column chromatography (silica gel 100–200 mesh, 15 %
EtOAc/hexane) to afford the title product as a colorless solid
(0.363 g, 95 %), m.p. 134–135 °C. 1H NMR (300 MHz, CDCl3): δ =
7.89 (d, J = 8.6 Hz, 3 H), 7.81 (d, J = 8.3 Hz, 3 H), 7.71 (d, J = 8.1 Hz,
3 H), 6.93 (d, J = 8.5 Hz, 3 H), 3.87 (s, 5 H), 3.55 (d, J = 6.1 Hz, 3 H),
3.45 ppm (d, J = 5.7 Hz, 3 H). 13C NMR (125 MHz, CDCl3): δ = 193.6,
164.1, 138.1, 132.8, 130.4, 129.6, 129.3, 128.8, 114.0, 55.6, 51.2,
30.9 ppm. (IR, neat): ν = 3017, 1678, 1313, 1250, 748 cm–1. HRMS
˜
(ESI): calcd. for [C16H15O4BrSNa]+ 404.97666; found 404.97669.
Experimental Section
3-[(4-Chlorophenyl)sulfonyl]-1-(4-methoxyphenyl)propan-1-
one (4):[24] Following the general procedure, the residue was puri-
fied by column chromatography (silica gel 100–200 mesh, 15 %
EtOAc/hexane) to afford the title product as a colorless solid
(0.304 g, 90 %), m.p. 130–131 °C. 1H NMR (500 MHz, CDCl3): δ =
7.89 (dd, J = 16.9, 8.2 Hz, 4 H), 7.55 (d, J = 8.6 Hz, 2 H), 6.94 (d, J =
8.9 Hz, 2 H), 3.88 (s, 3 H), 3.56 (t, J = 8.4 Hz, 2 H), 3.44 ppm (t, J =
8.4 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 193.7, 164.1, 140.8,
137.6, 130.4, 129.8, 129.5, 128.8, 114.0, 55.6, 51.3, 30.9 ppm. (IR,
General Methods: All solvents and reagents were used as received
from the suppliers. TLC was performed on Merck Kiesel gel 60, F254
plates with a layer thickness of 0.25 mm. Column chromatography
was performed on silica gel (100–200 mesh) by using a gradient of
EtOAc/hexane as the mobile phase. Melting points were deter-
mined with a Fisher John's melting point apparatus. IR spectra were
recorded with a Perkin–Elmer RX-1 FTIR system. 1H NMR spectro-
scopic data were collected at 300 (AVANCE & JCAMP), 400 (INOVA),
and 500 MHz (AVANCE & INOVA), whereas 13C NMR were recorded
at 75, 100, and 125 MHz. 1H NMR spectroscopic data are given as
chemical shifts in ppm followed by multiplicity (s: singlet; d: dou-
blet; dd: doublet of doublets; t: triplet; q: quartet; m: multiplet),
number of protons, and coupling constants. 13C NMR chemical
neat): ν = 3017, 1677, 1319, 1220, 721 cm–1. HRMS (ESI): calcd. for
˜
[C16H16O4ClS]+ 339.04523; found 339.04635.
1-(4-Methoxyphenyl)-3-(methylsulfonyl)propan-1-one (5): Fol-
lowing the general procedure, the residue was purified by column
Eur. J. Org. Chem. 2016, 3575–3583
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Full Paper
chromatography (silica gel 100–200 mesh, 15 % EtOAc/hexane) to
afford the title product as a colorless (0.220 g, 91 %), m.p. 136–
137 °C. 1H NMR (500 MHz, CDCl3): δ = 7.97 (d, J = 8.9 Hz, 2 H), 6.96
(d, J = 8.9 Hz, 2 H), 3.89 (s, 3 H), 3.57–3.48 (m, 4 H), 2.99 ppm (s, 3
H). 13C NMR (125 MHz, CDCl3): δ = 194.1, 164.2, 130.5, 128.8, 114.1,
CDCl3): δ = 194.3, 153.1, 145.0, 143.0, 136.1, 131.0, 130.0, 127.9,
105.4, 60.9, 56.3, 51.2, 31.0, 21.6 ppm. (IR, neat): ν = 3020, 1679,
˜
1321, 1216, 743 cm–1. HRMS (ESI): calcd. for [C19H23O6S]+ 379.12099;
found 379.12188.
4-(3-Tosylpropanoyl)benzonitrile (11): Following the general pro-
cedure, the residue was purified by column chromatography (silica
gel 100–200 mesh, 15 % EtOAc/hexane) to afford the title product
as a colorless solid (0.282 g, 90 %), m.p. 143–144 °C. 1H NMR
(500 MHz, CDCl3): δ = 8.03 (d, J = 8.5 Hz, 2 H), 7.82 (d, J = 8.3 Hz,
2 H), 7.79 (d, J = 8.5 Hz, 2 H), 7.38 (d, J = 8.0 Hz, 2 H), 3.57–3.48 (m,
4 H), 2.46 ppm (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 194.3, 145.2,
138.6, 135.8, 132.6, 130.1, 128.4, 127.9, 117.6, 116.9, 50.7, 31.8,
55.6, 49.5, 41.7, 30.8 ppm. (IR, neat): ν = 3020, 1672, 1314, 1214,
˜
742 cm–1. HRMS (ESI): calcd. for [C11H15O4S]+ 243.06856; found
243.06857.
1-Phenyl-3-tosylpropan-1-one (6):[28] Following the general pro-
cedure, the residue was purified by column chromatography (silica
gel 100–200 mesh, 15 % EtOAc/hexane) to afford the title product
as a colorless solid (0.253 g, 88 %), m.p. 134–135 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.92 (d, J = 7.3 Hz, 2 H), 7.83 (d, J = 8.2 Hz,
2 H), 7.59 (t, J = 7.4 Hz, 1 H), 7.47 (t, J = 6.1 Hz, 2 H), 7.37 (d, J =
8.0 Hz, 2 H), 3.59–3.44 (m, 4 H), 2.45 ppm (s, 3 H). 13C NMR (75 MHz,
CDCl3): δ = 195.6, 145.0, 136.0, 133.8, 133.2, 130.1, 128.8, 128.6,
21.6 ppm. (IR, neat): ν = 2925, 2232, 1692, 1315, 1218, 749 cm–1
.
˜
HRMS (ESI): calcd. for [C17H15O3NSNa]+ 336.06649; found 336.06764.
1-(4-Bromophenyl)-3-tosylpropan-1-one (12):[25] Following the
general procedure, the residue was purified by column chromatog-
raphy (silica gel 100–200 mesh, 15 % EtOAc/hexane) to afford the
title product as a colorless solid (0.340 g, 93 %), m.p. 156–157 °C;
1H NMR (300 MHz, CDCl3): δ = 7.79 (dd, J = 11.8, 8.4 Hz, 4 H), 7.60
(d, J = 8.5 Hz, 2 H), 7.36 (d, J = 8.0 Hz, 2 H), 3.55–3.41 (m, 4 H),
2.44 ppm (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 194.6, 145.1, 136.0,
134.6, 132.2, 130.1, 129.6, 129.1, 128.0, 51.0, 31.5, 21.7 ppm. (IR,
128.1, 51.1, 31.5, 21.7 ppm. (IR, neat): ν = 3021, 1686, 1317, 1215,
˜
742 cm–1. HRMS (ESI): calcd. for [C16H17O3S]+ 289.08929; found
289.18330.
1-(p-Tolyl)-3-tosylpropan-1-one (7):[25] Following the general pro-
cedure, the residue was purified by column chromatography (silica
gel 100–200 mesh, 15 % EtOAc/hexane) to afford the title product
as a pale yellow solid (0.275 g, 91 %), m.p. 110–111 °C. 1H NMR
(500 MHz, CDCl3): δ = 7.83 (d, J = 5.8 Hz, 2 H), 7.81 (d, J = 5.7 Hz,
2 H), 7.36 (d, J = 8.0 Hz, 2 H), 7.26 (d, J = 8.0 Hz, 2 H), 3.55–3.51 (m,
2 H), 3.47–3.42 (m, 2 H), 2.45 (s, 3 H), 2.41 ppm (s, 3 H). 13C NMR
(75 MHz, CDCl3): δ = 195.1, 145.0, 144.7, 136.1, 133.4, 130.0, 129.5,
neat): ν = 2926, 1691, 1317, 1215, 745 cm–1. HRMS (ESI): calcd. for
˜
[C16H16O3BrS]+ 366.99980; found 367.00150.
1-(Naphthalen-1-yl)-3-tosylpropan-1-one (13): Following the
general procedure, the residue was purified by column chromatog-
raphy (silica gel 100–200 mesh, 15 % EtOAc/hexane) to afford the
1
title product as a colorless solid (0.294 g, 87 %), m.p. 95–96 °C. H
128.2, 128.0, 51.2, 31.4, 21.7 ppm. (IR, neat): ν = 2924, 1681, 1316,
˜
1216, 771 cm–1. HRMS (ESI): calcd. for [C17H19O3S]+ 303.10494;
found 303.10535.
NMR (500 MHz, CDCl3): δ = 8.53 (d, J = 8.5 Hz, 1 H), 8.01 (d, J =
8.2 Hz, 1 H), 7.92 (dd, J = 7.2, 0.9 Hz, 1 H), 7.88–7.81 (m, 3 H), 7.59–
7.47 (m, 3 H), 7.35 (d, J = 8.1 Hz, 2 H), 3.66–3.61 (m, 2 H), 3.59–3.54
(m, 2 H), 2.43 ppm (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 198.8,
145.0, 136.1, 134.1, 134.0, 133.7, 130.1, 128.5, 128.4, 128.3, 128.1,
CCDC 1042343 (for 7) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre.
126.7, 125.7, 124.4, 51.4, 34.5, 21.7 ppm. (IR, neat): ν = 3020, 1682,
˜
1316, 1215, 745 cm–1. HRMS (ESI): calcd. for [C20H19O3S]+ 339.10494;
found 339.10591.
1-(4-Isopropylphenyl)-3-tosylpropan-1-one (8): Following the
general procedure, the residue was purified by column chromatog-
raphy (silica gel 100–200 mesh, 15 % EtOAc/hexane) to afford the
1-(Pyren-1-yl)-3-tosylpropan-1-one (14): Following the general
procedure, the residue was purified by column chromatography (sil-
ica gel 100–200 mesh, 15 % EtOAc/hexane as eluent) to afford the
title product as a pale yellow solid (0.325 g, 79 %), m.p. 146–147 °C.
1H NMR (300 MHz, CDCl3): δ = 8.89 (d, J = 9.4 Hz, 1 H), 8.39 (d, J =
8.1 Hz, 1 H), 8.28 (d, J = 7.6 Hz, 2 H), 8.25–8.18 (m, 3 H), 8.09 (dd,
J = 12.4, 5.2 Hz, 2 H), 7.88 (d, J = 8.3 Hz, 2 H), 7.37 (d, J = 8.0 Hz, 2
H), 3.75 (dd, J = 4.9, 3.5 Hz, 4 H), 2.44 ppm (s, 3 H). 13C NMR
(126 MHz, CDCl3): δ = 199.0, 145.0, 136.2, 134.5, 131.1, 130.4, 130.1,
130.0, 129.8, 129.6, 129.4, 128.1, 128.0, 127.4, 127.1, 126.7, 126.6,
1
title product as a colorless solid (0.287 g, 87 %), m.p. 81–82 °C. H
NMR (300 MHz, CDCl3): δ = 7.84 (t, J = 7.8 Hz, 4 H), 7.34 (dd, J =
14.7, 8.1 Hz, 4 H), 3.57–3.40 (m, 4 H), 3.04–2.88 (m, 1 H), 2.44 (s, 3
H), 1.26 ppm (d, J = 6.8 Hz, 6 H). 13C NMR (75 MHz, CDCl3): δ =
195.1, 155.3, 144.9, 136.0, 133.6, 129.9, 128.3, 127.9, 126.8, 51.1, 34.2,
31.3, 23.5, 21.6 ppm. (IR, neat): ν = 3020, 1682, 1317, 1215, 743 cm–1
.
˜
HRMS (ESI): calcd. for [C19H22O3SNa]+ 353.11819; found 353.11825.
1-(2,4-Dimethoxyphenyl)-3-tosylpropan-1-one (9): Following the
general procedure, the residue was purified by column chromatog-
raphy (silica gel 100–200 mesh, 25 % EtOAc/hexane) to afford the
title product as a colorless solid (0.285 g, 82 %), m.p. 115–116 °C.
1H NMR (300 MHz, CDCl3): δ = 7.80 (dd, J = 11.2, 8.5 Hz, 3 H), 7.36
(d, J = 8.0 Hz, 2 H), 6.53–6.43 (m, 2 H), 3.90 (s, 3 H), 3.86 (s, 3 H),
3.54–3.38 (m, 4 H), 2.45 ppm (s, 3 H). 13C NMR (125 MHz, CDCl3):
δ = 194.9, 165.1, 161.2, 144.7, 136.3, 133.0, 129.9, 128.1, 119.6, 105.5,
126.4, 125.0, 124.6, 124.1, 51.6, 32.0, 21.7 ppm. (IR, neat): ν = 2925,
˜
1677, 1305, 1215, 750 cm–1. HRMS (ESI): calcd. for [C26H21O3S]+
413.12059; found 413.12237.
(E)-1-Phenyl-5-tosylpent-1-en-3-one (15): Following the general
procedure, the residue was purified by column chromatography (sil-
ica gel 100–200 mesh, 15 % EtOAc/hexane) to afford the title prod-
uct as a colorless solid (0.251 g, 80 %), m.p. 151–152 °C. 1H NMR
(500 MHz, CDCl3): δ = 7.82 (d, J = 8.2 Hz, 2 H), 7.57 (d, J = 16.4 Hz,
1 H), 7.54 (dd, J = 7.3, 2.2 Hz, 2 H), 7.45–7.36 (m, 5 H), 6.71 (d, J =
16.2 Hz, 1 H), 3.47 (t, J = 7.9 Hz, 2 H), 3.19 (t, J = 7.9 Hz, 2 H),
2.46 ppm (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 195.3, 144.1, 131.0,
98.2, 55.6, 51.7, 32.0, 21.7 ppm. (IR, neat): ν = 3020, 1671, 1316,
˜
1215, 745 cm–1. HRMS (ESI): calcd. for [C18H21O5S]+ 349.11042;
found 349.11142.
3-Tosyl-1-(3,4,5-trimethoxyphenyl)propan-1-one (10): Following
the general procedure, the residue was purified by column chroma-
tography (silica gel 100–200 mesh, 25 % EtOAc/hexane) to afford
the title product as a colorless solid (0.302 g, 80 %), m.p. 136–
137 °C. 1H NMR (500 MHz, CDCl3): δ = 7.84 (dd, J = 8.1, 1.4 Hz, 2
130.1, 129.1, 128.5, 128.0, 125.1, 51.0, 33.1, 21.7 ppm. (IR, neat): ν =
˜
2925, 1690, 1316, 1214, 749 cm–1. HRMS (ESI): calcd. for
[C18H19O3S]+ 315.10494; found 315.10572.
H), 7.38 (d, J = 7.1 Hz, 2 H), 7.18 (d, J = 1.3 Hz, 2 H), 3.92 (d, J = 3-(Methylsulfonyl)-1-phenylpropan-1-one (16): Following the
1.7 Hz, 9 H), 3.54–3.49 (m, 4 H), 2.46 ppm (s, 3 H). 13C NMR (75 MHz,
general procedure, the residue was purified by column chromatog-
Eur. J. Org. Chem. 2016, 3575–3583
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3581
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
raphy (silica gel 100–200 mesh, 10 % EtOAc/hexane) to afford the 39.6, 37.4, 32.6, 31.0, 29.8, 25.8, 21.7, 20.9 ppm. (IR, neat): ν = 2924,
˜
title product as a colorless solid (0.184 g, 87 %), m.p. 135–137 °C.
1H NMR (500 MHz, CDCl3): δ = 8.03–7.95 (m, 2 H), 7.62 (t, J = 7.4 Hz,
1 H), 7.50 (t, J = 7.8 Hz, 2 H), 3.60 (t, J = 6.9 Hz, 2 H), 3.53 (t, J =
6.9 Hz, 2 H), 3.00 ppm (s, 3 H). 13C NMR (101 MHz, CDCl3): δ =
195.68, 135.71, 134.01, 128.91, 128.18, 77.37, 77.05, 76.74, 49.38,
1665, 1315, 1215, 749 cm–1. HRMS (ESI): calcd. for [C19H25O3S]+
333.15189; found 333.15266.
1-(4-Methoxyphenyl)-3-tosyl-2(2H1)propan-1-one (1-d1): Follow-
ing the general procedure, the residue was purified by column chro-
matography (silica gel 100–200 mesh, 15 % EtOAc/hexane) to afford
the title product as a colorless solid (0.274 g, 86 %), m.p. 101–
41.74, 31.22 ppm. (IR, neat): ν = 2928, 1618, 1315, 1217, 748 cm–1
.
˜
MS (ESI): calcd. for [C10H13O3S]+ 213; found 213.
1
102 °C. H NMR (300 MHz, CDCl3): δ = 7.89 (d, J = 8.7 Hz, 2 H), 7.82
4-Tosylbutan-2-one (17):[20] Following the general procedure, the
residue was purified by column chromatography (silica gel 100–
200 mesh, 10 % EtOAc/hexane) to afford the title product as a color-
(d, J = 8.0 Hz, 2 H), 7.36 (d, J = 7.8 Hz, 2 H), 6.92 (d, J = 8.7 Hz, 2
H), 3.86 (s, 3 H), 3.52 (m, 2 H), 3.41 (m, 1 H), 2.44 ppm (s, 3 H). 13C
NMR (125 MHz, CDCl3): δ = 193.9, 163.9, 144.8, 136.0, 130.3, 129.9,
128.8, 127.9, 113.8, 55.5, 51.1 (t), 30.9, 30.7, 30.6, 21.6 ppm. (IR,
1
less solid (0.183 g, 81 %), m.p. 75–76 °C. H NMR (500 MHz, CDCl3):
neat): ν = 2923, 1672, 1313, 1253, 727 cm–1. HRMS (ESI): calcd. for
δ = 7.79 (d, J = 7.3 Hz, 2 H), 7.36 (d, J = 8.3 Hz, 2 H), 3.35 (t, J =
7.7 Hz, 2 H), 2.91 (t, J = 7.7 Hz, 2 H), 2.45 (s, 3 H), 2.17 ppm (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 204.1, 145.1, 130.1, 129.7, 128.0, 50.6,
˜
[C17H17DO4S]+ 320.10613; found 320.10643.
36.0, 32.0, 21.7 ppm. (IR, neat): ν = 2924, 1718, 1316, 1215, 750 cm–1
.
˜
HRMS (ESI): calcd. for [C11H14O3SNa]+ 249.05559; found 249.05572.
Acknowledgments
The authors thank the Director of CSIR – Indian Institute of
Chemical Technology, Hyderabad for generous support and the
Council of Scientific and Industrial Research (CSIR), New Delhi,
for funding through the program TREAT XII FYP (BSC-0116).
V. M. thanks the CSIR for a Senior Research Fellowship.
1-Tosylhexan-3-one (18): Following the general procedure, the res-
idue was purified by column chromatography (silica gel 100–
200 mesh, 10 % EtOAc/hexane) to afford the title product as a color-
1
less solid (0.211 g, 83 %), m.p. 69–70 °C. H NMR (500 MHz, CDCl3):
δ = 7.77 (d, J = 8.1 Hz, 2 H), 7.35 (d, J = 8.2 Hz, 2 H), 3.36 (t, J =
7.8 Hz, 2 H), 2.87 (t, J = 7.5 Hz, 2 H), 2.44 (s, 3 H), 2.39 (t, J = 7.3 Hz,
2 H), 1.59–1.52 (m, 2 H), 0.88 ppm (t, J = 7.5 Hz, 3 H). 13C NMR
(125 MHz, CDCl3): δ = 206.1, 145.0, 136.1, 130.0, 128.0, 50.6, 44.7,
Keywords: Allylic compounds · Enones · Oxygen ·
Palladium · Sulfur
35.1, 32.0, 22.7, 21.6, 13.6 ppm. (IR, neat): ν = 2926, 1718, 1316,
˜
1215, 729 cm–1. HRMS (ESI): calcd. for [C13H18O3SNa]+ 277.08689;
found 277.08668.
1-Tosyloctan-3-one (19):[25] Following the general procedure, the
residue was purified by column chromatography (silica gel 100–
200 mesh, 10 % EtOAc/hexane) to afford the title product as a color-
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1
less solid (0.254 g, 90 %), m.p. 65–66 °C. H NMR (300 MHz, CDCl3):
δ = 7.78 (d, J = 8.1 Hz, 2 H), 7.36 (d, J = 8.0 Hz, 2 H), 3.37 (t, J =
7.5 Hz, 2 H), 2.87 (t, J = 7.5 Hz, 2 H), 2.44 (s, 3 H), 2.40 (t, J = 7.4 Hz,
2 H), 1.59–1.47 (m, 2 H), 1.34–1.17 (m, 4 H), 0.87 ppm (t, J = 6.8 Hz,
3 H). 13C NMR (125 MHz, CDCl3): δ = 206.4, 145.0, 136.0, 130.0,
128.0, 50.6, 42.8, 35.0, 31.2, 23.3, 22.4, 21.6, 13.9 ppm. (IR, neat): ν =
˜
2928, 1717, 1317, 1215, 745 cm–1. HRMS (ESI) calcd. for [C15H23O3S]+
283.13624; found 283.13660.
(S)-1-[4-(Prop-1-en-2-yl)cyclohex-1-en-1-yl]-3-tosylpropan-1-
one (20): Following the general procedure, the residue was purified
by column chromatography (silica gel 100–200 mesh, 10 % EtOAc/
hexane) to afford the title product as a colorless solid (0.262 g,
79 %), m.p. 80–81 °C. 1H NMR (500 MHz, CDCl3): δ = 7.79 (d, J =
8.2 Hz, 2 H), 7.36 (d, J = 8.0 Hz, 2 H), 6.95 (t, J = 4.3 Hz, 1 H), 4.77
(s, 1 H), 4.71 (s, 1 H), 3.41 (t, J = 8.2 Hz, 2 H), 3.14 (t, J = 7.9 Hz, 2
H), 2.45 (s, 3 H), 2.41–2.38 (m, 1 H), 2.21–2.04 (m, 5 H), 1.89–1.86
(m, 1 H), 1.74 ppm (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 196.0,
148.4, 144.9, 140.8, 138.3, 136.2, 130.0, 128.0, 109.5, 51.3, 40.0, 32.0,
31.4, 26.7, 21.7, 20.7 ppm. (IR, neat): ν = 2926, 1667, 1317, 1214,
˜
744 cm–1. HRMS (ESI): calcd. for [C19H25O3S]+ 333.15189; found
333.15269.
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1
77 %). H NMR (500 MHz, CDCl3): δ = 7.79 (d, J = 8.2 Hz, 2 H), 7.36
(d, J = 8.1 Hz, 2 H), 6.80 (s, 1 H), 3.40 (dd, J = 9.4, 5.8 Hz, 2 H), 3.20–
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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Received: April 20, 2016
Published Online: July 4, 2016
Eur. J. Org. Chem. 2016, 3575–3583
www.eurjoc.org
3583
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim