Synthesis of Functionalized β-Keto Arylthioethers by the Aryne Induced [2,3] Stevens Rearrangement of Allylthioethers

Article abstract of DOI:10.1021/acs.joc.7b00479

A mild and transition-metal-free synthesis of β-keto arylthioethers has been developed by the aryne triggered [2,3] Stevens rearrangement of allylthioethers. The key sulfur ylide intermediate for the rearrangement was formed by the S-arylation of allylthi

Full text of DOI:10.1021/acs.joc.7b00479

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Synthesis of Functionalized #-Keto Arylthioethers by the
Aryne Induced [2,3] Stevens Rearrangement of Allylthioethers
Manikandan Thangaraj, Rahul N Gaykar, Tony Roy, and Akkattu T. Biju
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b00479 • Publication Date (Web): 28 Mar 2017
Downloaded from http://pubs.acs.org on March 29, 2017
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Synthesis of Functionalized β-Keto Arylthioethers by the Aryne
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Induced [2,3] Stevens Rearrangement of Allylthioethers
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Manikandan Thangaraj, Rahul N. Gaykar, Tony Roy and Akkattu T. Biju*
Organic Chemistry Division, CSIRꢀNational Chemical Laboratory, Dr. Homi Bhabha Road,
Pune 411008, India
Academy of Scientific and Innovative Research (AcSIR), New Delhi 110020, India
Eꢀmail: at.biju@ncl.res.in
ABSTRACT: A mild and transitionꢀmetalꢀfree synthesis of βꢀketo arylthioethers has been
developed by the aryne triggered [2,3] Stevens rearrangement of allylthioethers. The key sulfur
ylide intermediate for the rearrangement was formed by the Sꢀarylation of allylthioethers with
arynes generated from 2ꢀ(trimethylsilyl)aryl triflates using CsF. Later, the reaction products are
converted into valuable heterocycles in two steps.
Organosulfur compounds are endowed with diverse applications in pharmaceutical
chemistry and crop protection, and have attracted considerable attention from both industry and
academia.1 Among the organosulfur compounds, the βꢀketo thioethers are important as they are
valuable core structure in various biologically active molecules. For instance, the indane 1,3ꢀ
dione derived aryl thioethers (A) has been known as serine protease inhibitor (Figure 1).2
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Moreover, the cyclohexanone containing thioether (B) is a precursor for the synthesis of
Gabosines, epoforminand epiepoformin,3 and the benzothiazine derivative (C) shows antiꢀ
inflammatory activity.4 In addition, the 2ꢀamino aryl thioethers (D) shows antitumor activity.5 In
view of the relevance of these molecules, synthesis of facile and straightforward synthetic routes
to βꢀketo aryl allylthioethers are highly desirable. βꢀKetothioethers are traditionally synthesized
either by the reaction of diazocarbonyl compounds with thiols via the SꢀH insertion6 or by the Sꢀ
alkylation of αꢀhaloketones.7,8 Herein, we report the synthesis of functionalized βꢀketo
arylthioethers by the [2,3] Stevens rearrangement of allylthioethers triggered by arynes.9
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Figure 1. Biologically active molecules having βꢀketo thioethers moiety
Recently, the Studer group demonstrated the reaction of arynes with vinyl thioethers
(having no αꢀCꢀH protons) leading to the highly selective formation of trisubstituted olefins
(Scheme 1, eq 1).10a The reaction proceeds via the generation of cyclic sulfur ylides by the [3+2]
cycloaddition of vinyl thioethers with arynes, which undergoes proton transfer and βꢀelimination
to afford the functionalized olefin.11 In this context we envisioned that the reaction of arynes
with allylthioethers such as 1 having an αꢀCꢀH proton could generate the acyclic sulfur ylide
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intermediate B via the aryl anion intermediate A. The [2,3] Stevens rearrangement12 of ylide B
could lead to the formation of functionalized βꢀketo arylthioethers (eq 2). The acidity of αꢀCꢀH
proton in 1 will be crucial for the sulfur ylide generation and the subsequent rearrangement. It is
noteworthy that the related aryne induced [2,3] Stevens rearrangement of tertiary allylic amines
for the synthesis of functionalized homoallylic amines was demonstrated independently by Gu,
Tian and coꢀworkers,13 Sweeney and coꢀworkers,14 and by us (eq 3).15,16 Moreover, Greaney and
coꢀworkers uncovered the azaꢀClaisen rearrangement of tertiary allyl amines triggered by arynes
for the synthesis of 2ꢀallyl anilines.17,18
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Scheme 1. Reaction of Arynes with Vinyl Thioethers and [2,3] Stevens Rearrangement Involving
Arynes
The present study was initiated by treating the allylthioether 1a with aryne generated
from 2ꢀ(trimethylsilyl)aryl triflate 2a19 using CsF as the fluoride source in CH3CN solvent.
Interestingly, under these conditions, the βꢀketo arylthioethers 3a was formed in 78% yield in 12
h (Scheme 2). During the search for the suitable allylthioether substrate, it was found that the
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reaction of allyl benzylthioether with arynes resulted in the formation of low yield of the
rearranged product. This indicates that the carbonyl moiety in 1a was essential for the reactivity
as it increases the acidity of α CꢀH protons, which enables the smooth generation of the sulfur
ylide. The reactions performed using KF in the presence of an 18ꢀcrownꢀ6 as additive and
tetrabutyl ammonium fluoride (TBAF) resulted in inferior results.20 It may be noted that closely
related [1,2] Stevens rearrangement of thioethers for the synthesis of functionalized βꢀketo
thioethers has been demonstrated very recently by Guo, He and coꢀworkers.21
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Scheme 2. Aryne Triggered [2,3] Stevens Rearrangement of Allylthioether
With the reaction conditions for the [2,3] Stevens rearrangement in hand, we then
explored the substrate scope of this reaction. First, we evaluated the scope of the reaction using
various allylthioethers having a benzoyl moiety at the βꢀposition of allylthioether (Scheme 3). A
series of electronꢀreleasing and ꢀwithdrawing groups at the 4ꢀposition of benzene ring of the
benzoyl moiety are well tolerated and in all cases, the βꢀketo arylthioethers are formed in good
yields (3b-3f). Moreover, substrates having substitution at the 3ꢀposition as well as 2ꢀposition of
the aryl ring of benzoyl moiety underwent smooth rearrangement reaction to form the expected
aryl homoallyl thioethers in moderate to good yields (3g-3l). Interestingly, the thioether having
the βꢀheteroaryl keto group also furnished the desired product 3m in 73% yield. In addition,
disubstitution at the aryl moiety also did not affect the outcome of this aryne triggered
rearrangement reaction (3n-3q).22
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Scheme 3. Scope of Allylthioethers in the Aryne Induced [2,3] Stevens Rearrangement.General
conditions: 1 (0.50 mmol), 2a (0.75 mmol), CsF (3.0 equiv), CH3CN (3.0 mL), 25 °C and 12 h.
Yields of the isolated products are given.
Next, we examined the scope of the reaction using cyclic ketoneꢀderived allylthioethers
with a view to synthesize quaternary βꢀketo allylthioethers (Scheme 4). Gratifyingly, the allyl
thioethers synthesized from indanone (1r) and tetralone (1s) underwent smooth aryneꢀinduced
Stevens rearrangement leading to the formation of highly functionalized aryl allylthioethers 3r
and 3s in good yields (eq 4). Interestingly, this rearrangement is not limited to allylthioethers
having aryl ketones at the βꢀposition, but instead other cyclic ketonesꢀderived allylthioethers (1t-
1v) and an acyclic ketoneꢀderived thioethers (1w) were also useful for the sulfur ylide generation
followed by [2,3] Stevens rearrangement sequence and in all cases, the thioethers with a
quaternary centre (3t-3w) were formed in moderate to good yields (eq 5,6).
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Scheme 4. Synthesis of Quaternary βꢀKeto Aryl Allylthioethers. General conditions: 1 (0.50
mmol), 2a (0.75 mmol), CsF (3.0 equiv), CH3CN (3.0 mL), 25 °C and 12 h. Yields of the
isolated products are given.
The scope of this [2,3] rearrangement was also examined with various arynes (Table 1).
Differently substituted and electronically dissimilar symmetrical arynes generated from the
corresponding triflate precursors (2b-2e) reacted with the βꢀbenzoyl allyl thioether 1a under the
present reaction conditions to afford the expected aryl thioethers (3x-3aa) in good yields. It is
noteworthy that the unsymmetrical 3ꢀmethoxy benzyne generated from the precursor 2f afforded
a single regioisomer 3ab in 50% yield. Additionally, the reaction of 1a with unsymmetrical 4ꢀ
methyl benzyne generated from the triflate 2g resulted in the formation of two regioisomers 3ac
and 3ac’ in 72% yield and 1:1 ratio. Furthermore, the reaction using 4ꢀfluoro benzyne resulted in
the formation of two regioisomeric aryl allylthioethers 3ad and 3ad’ in 71% yield and 2.6:1 ratio
thus demonstrating the versatility of this rearrangement reaction.
Table 1.Variation of the Aryne Moiety
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General conditions: 1a (0.50 mmol), 2 (0.75 mmol), CsF (3.0 equiv), CH3CN (3.0 mL), 25 °C
and 12 h. Yields of the isolated products are given. aThe regioisomer ratio was determined either
by GC or 1H NMR analysis of crude reaction mixture.
The synthetic utility of the βꢀketo arylthioethers has been demonstrated by the conversion
of these compounds to valuable heterocycles in two steps. The ozonolysis of 3a resulted in the
formation of the 1,4ꢀdicarbonyl compound 4 containing the thioethers moiety in 86% yield
(Scheme 5). Treatment of the dicarbonyl compound 4 in the presence of Conc. HCl at 0 °C
afforded the disubstituted furan 5 in 79% yield. Moreover, the reaction of 4 with NH4OAc
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resulted in the formation of the disubstituted pyrrole 6 in 81% yield. In addition, treatment of 4
with hydrazine hydrate at 80 °C furnished the 3ꢀphenyl pyridazine 7 in 85% yield.
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Scheme 5. Synthesis of Heterocycles from Allylthioethers
We also tested the feasibility of this reaction using allylthioether having a substituent at
the allylic position. Treatment of βꢀketo cinnamyl thioether 1ae with aryne generated from 2a
under the present reaction conditions furnished the arylthioethers 3ae in 42% yield and 2:1 dr
(Scheme 6). Additional experiments to improve the yield and dr of this transformation returned
inferior results.
Scheme 6. Aryne Induced [2,3] Stevens Rearrangement of Cinnamyl Thioether
In conclusion, we have developed a transitionꢀmetalꢀfree procedure for the synthesis of
βꢀketo arylthioethers by the aryne triggered [2,3] Stevens rearrangement of allylthioethers. The
reaction proceeds via the generation of the sulfur ylide intermediate from arynes and
allylthioethers and results in the formation of a new carbonꢀcarbon and carbonꢀsulfur bonds. A
series of allylthioethers and differently substituted arynes are tolerated under the present reaction
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conditions. Moreover, the reaction products are converted into arylheteroaryl thioethers in a twoꢀ
step procedure.
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Experimental Section
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General Information: Unless otherwise specified, all reactions were carried out under an
atmosphere of argon in flameꢀdried reaction vessels with Teflon screw caps. 25 °C corresponds
to the room temperature of the lab when the experiments were carried out. THF was freshly
purified by distillation over Naꢀbenzophenone and was transferred under argon. 18ꢀCrownꢀ6 was
recrystallized from dry CH3CN and KF was dried by heating at 110 °C for 12 h and left to cool
under argon and stored in argon filled gloveꢀbox. The 2(trimethylsilyl)phenyl
trifluoromethanesulfonate 1a and the other symmetric and unsymmetric aryne precursors were
13
synthesized following literature procedure.19 1H and C NMR spectra were recorded in CDCl3
as solvent. Chemical shifts (δ) are given in ppm. The residual solvent signals were used as
references and the chemical shifts converted to the TMS scale (CDCl3: δH = 7.26 ppm, δC =
77.16 ppm). HRMS measurements were carried out using ESI method and ionꢀtrap mass
analyzer.
General Procedure for the preparation of Allylthioethers
Following the modified literature procedure,23 treatment of phenacyl bromide (1.0 g, 1.0
equiv) with the corresponding allyl mercaptan (1.5 equiv) in presence of potassium carbonate
(2.0 equiv) and acetonitrile as a solvent at 60 °C for 12 h afforded the corresponding 2ꢀ
(allylthio)ꢀ1ꢀphenylethanꢀ1ꢀone substrate. The data are matching with the corresponding
literature procedure.24
General Procedure for the Aryne [2,3]-Stevens Rearrangement
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To a flameꢀdried screwꢀcapped test tube equipped with a magnetic stir bar was added the
CsF (228 mg, 1.5 mmol) in a glove box. The mixture was dissolved in CH3CN (3.0 mL) under
argon atmosphere. 2ꢀ(Allylthio)ꢀ1ꢀphenylethanꢀ1ꢀone 1 (0.50 mmol) was added outside the glove
box under argon atmosphere. To the stirring solution, aryne precursor 2 (0.75mmol) was added.
Then the reaction mixture was allowed to react at 25 °C for 12 h. After 12 h, the reaction was
stopped, the solvent was evaporated and the crude residue preꢀadsorbed on silica gel and purified
by flash column chromatography by using Pet. ether /EtOAc system on silica gel to afford the
corresponding 1ꢀphenylꢀ2ꢀ(phenylthio)pentꢀ4ꢀenꢀ1ꢀones 3 in moderate to good yields.
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1-Phenyl-2-(phenylthio)pent-4-en-1-one (3a):25 (yellow oil, 0.104 g, 78% yield). Rf (Pet. ether
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/EtOAc = 95/05): 0.38; H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 7.4 Hz, 2H), 7.59 (t,J = 7.5
Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.40ꢀ7.28 (m, 5H), 5.97ꢀ5.89 (m, 1H), 5.19ꢀ5.12 (m, 2H), 4.55
(t, J = 7.3 Hz, 1H), 2.85ꢀ2.79 (m, 1H), 2.67ꢀ2.62 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 195.2,
136.1, 134.8, 133.1, 131.6, 131.1, 129.2, 129.0, 128.8, 128.6, 128.6, 127.1, 117.8, 50.8, 35.1.
+
HRMS (ESI) calculated [M+H] for C17H17OS: 269.09946, found: 269.09955. FTIR (cm-1)
3018, 1678, 1597, 1580, 1474, 1439, 1344, 1276, 1025, 924.
1-(4-Methoxyphenyl)-2-(phenylthio)pent-4-en-1-one (3b): (colorless oil, 0.121 g, 81% yield).
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Rf (Pet. ether /EtOAc = 90/10): 0.45; H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.5 Hz, 2H),
7.30 (t, J = 6.8 Hz, 2H), 7.29 (d, J = 7.3 Hz, 3H), 6.93 (d, J = 8.6 Hz, 2H), 5.93 – 5.84 (m, 1H),
5.11 (dd, J1 = 18.7 Hz, J2 = 13.9 Hz, 2H), 4.50 (t, J = 7.2 Hz, 1H), 3.88 (s, 3H), 2.82 – 2.75 (m,
1H), 2.64 – 2.57 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 194.1, 163.6, 135.0, 134.6, 132.0,
+
131.0, 129.0, 128.6, 117.7, 113.8, 55.5, 50.7, 35.3. HRMS (ESI) calculated [M+H] for
C18H19O2S: 299.1100, found: 299.1095. FTIR (cm-1) 3019, 2937, 2835, 2401, 1742, 1642, 1514,
1464, 1373, 1216, 1030, 959, 772.
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2-(Phenylthio)-1-(p-tolyl)pent-4-en-1-one (3c):25 (viscous yellow oil, 0.110 g, 78% yield). Rf
(Pet. ether /EtOAc = 95/05): 0.23; 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.1 Hz,2H), 7.40 ꢀ
7.38 (m, 2H), 7.34 ꢀ 7.26 (m, 5H), 5.97 ꢀ 5.86 (m, 1H), 5.17 ꢀ 5.09 (m, 2H), 4.53 (t, J = 7.2 Hz,
1H), 2.84 ꢀ 2.76 (m, 1H), 2.66 ꢀ 2.59 (m, 1H), 2.44 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
194.9, 144.0, 134.9, 134.7, 133.5, 131.7, 129.3, 129.0, 128.7, 128.7, 117.7, 77.1, 50.8, 35.2, 21.7.
HRMS (ESI) calculated [M+H] + for C18H19OS: 283.1151, found: 283.1155. FTIR (cm-1) 3018,
1673, 1607, 1573, 1438, 1340, 1216, 1025, 924.
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1-(4-Bromophenyl)-2-(phenylthio)pent-4-en-1-one (3d): (pale yellow oil 0.130 g, 75 %
yield). Rf (Pet. ether /EtOAc = 95/05): 0.39; 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.5 Hz,
2H), 7.58 (d, J = 8.5 Hz, 2H), 7.34ꢀ7.27 (m, 5H), 5.94ꢀ5.84 (m, 1H), 5.16ꢀ5.09 (m, 2H), 4.43 (t, J
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= 7.5 Hz, 1H), 2.80ꢀ2.73 (m, 1H), 2.63ꢀ2.56 (m, 1H). C NMR (100 MHz, CDCl3) δ 194.1,
135.0, 134.9, 134.7, 131.9, 131,2, 130.2, 129.1, 129.1, 128.3, 118.0, 50.9, 34.9. HRMS (ESI)
calculated [M+H] + for C17H16OBrS: 347.0100, found: 347.0092. FTIR (cm-1) 3019, 1679, 1585,
1475, 1438, 1396, 1273, 1217, 1071, 1010,926, 772, 691, 669.
1-(4-Chlorophenyl)-2-(phenylthio)pent-4-en-1-one (3e): (pale yellow oil, 0.104 g, 69% yield).
1
Rf (Pet. ether /EtOAc = 95/05): 0.41; H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.5 Hz, 2H),
7.44 (d, J = 8.5 Hz, 2H), 7.37ꢀ7.29 (m, 5H), 5.96ꢀ5.86 (m, 1H), 5.18ꢀ5.11 (m, 2H), 4.46 (t, J =
7.3 Hz, 1H), 2.82ꢀ2.75 (m, 1H), 2.66ꢀ2.59 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 194.0,
139.6, 135.0, 134.7, 134.4, 131.2, 130.1, 129.1, 129.1, 129.0, 118.0, 50.9, 35.0. HRMS (ESI)
calculated [M+H] + for C17H16OClS: 303.0605, found: 303.0600. FTIR (cm-1) 3019, 1678, 1589,
1477, 1438, 1400, 1274, 1218, 1093, 1045, 927, 848, 772, 669.
1-(4-Fluorophenyl)-2-(phenylthio)pent-4-en-1-one (3f): (viscous yellow oil, 0.110 g, 77%
yield). Rf (Pet. ether /EtOAc = 95/05): 0.30; 1H NMR (400 MHz, CDCl3) δ 7.98 ꢀ 7.95 (m, 2H),
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7.37 ꢀ 7.28 (m, 5H), 7.12 (t, J = 8.2 Hz, 2H), 5.95ꢀ5.85 (m, 1H), 5.17 ꢀ 5.10 (m, 2H), 4.47 (t, J =
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7.1 Hz, 1H), 2.82 ꢀ 2.75 (m, 1H), 2.65 ꢀ 2.58 (m, 1H). C NMR (100 MHz, CDCl3) δ 193.7,
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165.8 (d, J = 254.1 Hz), 134.9, 134.8, 131.3 (d, J = 9.6 Hz), 129.1, 129.0, 117.9, 115.7 (d, J =
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21.7 Hz), 50.9, 35.1. HRMS (ESI) calculated [M+H] for C17H16OFS: 287.09004, found:
287.08997. FTIR (cm-1) 3077, 3018, 1678, 1598, 1474, 1300, 1157, 924, 851.
1-(3-Methoxyphenyl)-2-(phenylthio)pent-4-en-1-one (3g): (colorless oil, 0.110 g, 74% yield).
Rf (Pet. ether /EtOAc = 90/10): 0.43; 1H NMR (400 MHz, CDCl3) δ 7.44 – 7.33 (m, 2H), 7.30 –
7.16 (m, 6H), 7.02 (d, J = 7.8 Hz, 1H), 5.83 – 5.77 (m, 1H), 5.07 – 4.99 (m, 2H), 4.40 (t, J = 7.2
Hz, 1H), 3.74 (s, 3H), 2.72 – 2.64 (m, 1H), 2.55 – 2.48 (m, 1H). 13C NMR (100 MHz, CDCl3) δ
195.1, 159.9, 137.5, 134.8, 131.7, 129.6, 129.1, 128.8, 121.1, 119.7, 117.9, 113.0, 55.5, 51.0,
35.2. HRMS (ESI) calculated [M+H] + for C18H19O2S: 299.1100, found: 299.1096. FTIR (cm-1)
3019, 2937, 2401, 1742, 1514, 1443, 1373, 1241, 1216, 1030, 926, 815, 772.
2-(Phenylthio)-1-(m-tolyl)pent-4-en-1-one (3h): (yellow oil, 0.055 g, 40 % yield). Rf (Pet. ether
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/EtOAc = 95/05): 0.36; H NMR (400 MHz, CDCl3) δ 7.75ꢀ7.71 (m, 2H), 7.39ꢀ7.28 (m, 7H),
5.96ꢀ5.86 (m, 1H), 5.17ꢀ5.12 (m, 2H), 4.52 (t, J = 7.3 Hz, 1H), 2.82ꢀ2.75 (m, 1H), 2.65ꢀ2.58 (m,
1H), 2.39 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 195.5, 138.4, 136.2, 134.9, 133.9, 131.8,
129.2, 129.0, 128.8, 128.5, 125.8, 117.8, 50.9, 35.1, 21.4. HRMS (ESI) calculated [M+H] + for
C18H19OS: 283.1151, found: 283.1146. FTIR (cm-1) 3018, 1676, 1640, 1602, 1584, 1475, 1438,
1339, 1279, 1256, 1216, 924, 769, 691, 668.
1-(3-Fluorophenyl)-2-(phenylthio)pent-4-en-1-one (3i): (pale yellow oil, 0.080 g, 56% yield).
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Rf (Pet. ether /EtOAc = 95/05): 0.33; H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.1 Hz, 1H),
7.64 ꢀ 7.61 (m, 1H), 7.46ꢀ7.40 (m, 1H), 7.37 ꢀ 7.25 (m, 6H), 5.46 ꢀ 5.40 (m, 1H), 5.17 ꢀ 5.10 (m,
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2H), 4.44 (t, J = 7.6 Hz, 1H), 2.81 ꢀ 2.74 (m, 1H), 2.65 ꢀ 2.58 (m, 1H). C NMR (100 MHz,
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CDCl3) δ 193.8, 162.9 (d, J = 248.6 Hz), 138.3, 135.1, 134.6, 131.1, 130.3 (d, J = 8.1 Hz),
129.1, 124.3, 124.3, 120.1 (d, J = 21.8 Hz), 118.0, 115.5 (d, J = 22.7 Hz), 51.1, 34.9. HRMS
(ESI) calculated [M+H] + for C17H16OFS: 287.0900, found: 287.0893. FTIR (cm-1) 3077, 3018,
1681, 1588, 1483, 1339, 1273, 1216, 1148, 994.
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3-(2-(Phenylthio)pent-4-enoyl)benzonitrile (3j): (pale yellow oil, 0.090 g, 61 % yield). Rf (Pet.
ether /EtOAc = 95/05): 0.12; 1H NMR (400 MHz, CDCl3) δ 8.14ꢀ8.12 (m, 2H), 7.82 (d, J= 7.75
Hz, 1H), 7.57 (t, J=8.2 Hz, 1H), 7.38ꢀ7.27 (m, 5H), 5.94ꢀ5.78 (m, 1H), 5.17ꢀ5.11 (m, 2H), 4.40
(t, J = 7.2 Hz, 1H), 2.80ꢀ2.72 (m, 1H), 2.65ꢀ2.58 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 192.9,
137.0, 135.9, 135.2, 134.4, 132.6, 132.3, 130.7, 129.6, 129.4, 129.2, 118.3, 117.9, 113.1, 51.1,
34.6. HRMS (ESI) calculated [M+H] + for C18H16ONS: 294.0947, found: 294.0940. FTIR (cm-
1) 3019, 2977, 2349, 1686, 1600, 1525, 1477, 1425, 1215, 1045, 928, 877, 849, 755, 669.
1-(2-Methoxyphenyl)-2-(phenylthio)pent-4-en-1-one (3k): (colorless oil, 0.079 g, 53% yield).
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Rf (Pet. ether /EtOAc = 90/10): 0.39; H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 7.7 Hz, 1H),
7.35 (t, J = 7.8 Hz, 1H), 7.25 – 7.08 (m, 5H), 6.93 (t, J = 7.4 Hz, 1H), 6.79 (d, J = 8.3 Hz, 1H),
5.92 ꢀ 5.81 (m, 1H), 5.03 (dd, J1 = 17.7 Hz, J2 = 14.1 Hz, 2H), 4.72 (t, J = 7.2 Hz, 1H), 3.68 (s,
13
3H), 2.72 – 2.65 (m, 1H), 2.47 – 2.39 (m, 1H). C NMR (100 MHz, CDCl3) δ 197.4, 158.0,
135.4, 134.1, 133.5, 132.5, 131.4, 128.7, 128.2, 127.4, 120.9, 117.2, 111.5, 55.5, 55.2, 34.7.
HRMS (ESI) calculated [M+H] + for C18H19O2S: 299.1100, found: 299.1096. FTIR (cm-1) 3015,
2981, 1642, 1600, 1503, 1455, 1423, 1347, 1229, 1131, 992, 872, 752.
1-(2-Bromophenyl)-2-(phenylthio)pent-4-en-1-one (3l): (yellow oil, 0.050 g, 34% yield). Rf
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(Pet. ether /EtOAc = 95/05): 0.3; H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 7.9 Hz, 1H), 7.34
(d, J = 7.3 Hz, 1H), 7.23ꢀ7.19 (m, 3H), 7.17ꢀ7.10 (m, 4H), 5.94ꢀ5.82 (m, 1H), 5.11ꢀ5.03 (m, 2H),
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4.37 (t, J = 7 Hz, 1H), 2.74ꢀ2.67 (m, 1H), 2.51ꢀ2.44 (m, 1H). C NMR (100 MHz, CDCl3) δ
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198.4, 140.6, 134.5, 134.0, 133.5, 132.1, 131.7, 130.2, 129.0, 128.5, 127.3, 119.4, 118.2, 55.1,
34.4. HRMS (ESI) calculated [M+H] + for C17H16OBrS: 347.0100, found: 347.0096. FTIR (cm-
1) 3019, 2977, 1693, 1640, 1587, 1525, 1476, 1430, 1216, 1045, 1027, 927, 773, 690, 669.
2-(Phenylthio)-1-(thiophen-2-yl)pent-4-en-1-one (3m): (yellow oil, 0.100 g, 73% yield). Rf
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(Pet. ether /EtOAc = 95/05): 0.31; H NMR (400 MHz, CDCl3) δ 7.65ꢀ7.62 (m, 2H), 7.43ꢀ7.41
(m, 2H), 7.31ꢀ7.29 (m, 3H), 7.10ꢀ7.07 (m, 1H), 5.94ꢀ5.84 (m, 1H), 5.18ꢀ5.09 (m, 2H), 4.35ꢀ4.31
(m, 1H), 2.80ꢀ2.75 (m, 1H), 2.64ꢀ2.57 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 189.0, 143.2,
134.6, 134.1, 132.3, 129.1, 128.8, 128.1, 118.0, 53.0, 35.3. HRMS (ESI) calculated [M+H] + for
C15H15OS2: 275.0559, found: 275.0564. FTIR (cm-1) 3018, 1657, 1583, 1516, 1475, 1438, 1345,
1218, 1066, 926.
1-(Naphthalen-2-yl)-2-(phenylthio)pent-4-en-1-one (3n): (yellow oil, 0.095 g, 60% yield). Rf
(Pet. ether /EtOAc = 95/05): 0.28; 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.1 Hz, 2H), 7.40
ꢀ 7.38 (m, 2H), 7.34 ꢀ 7.26 (m, 5H), 5.97 ꢀ 5.86 (m, 1H), 5.17 ꢀ 5.09 (m, 2H), 4.53 (t, J = 7.2 Hz,
1H), 2.84 ꢀ 2.76 (m, 1H), 2.66 ꢀ 2.59 (m, 1H), 2.44 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
198.9, 135.8, 134.7, 134.4, 134.0, 132.7, 132.4, 130.8, 128.9, 128.5, 128.4, 127.9, 127.0, 126.6,
+
125.9, 124.2, 118.2, 55.0, 35.6. HRMS (ESI) calculated [M+H] for C21H19OS: 319.1151,
found: 319.1145. FTIR (cm-1) 3019, 1677, 1583, 1509, 1476, 1328, 1215, 1087, 1025.
1-(3,4-Dimethoxyphenyl)-2-(phenylthio)pent-4-en-1-one (3o): (pale yellow oil, 0.103 g, 63%
yield). Rf (Pet. ether /EtOAc = 70/30): 0.48; 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.7 Hz,
1H), 7.49 (s, 1H), 7.39 ꢀ 7.37 (m, 2H), 7.30 ꢀ 7.28 (m, 3H), 6.86 (d, J = 8.2 Hz, 1H), 5.94 ꢀ 5.84
(m, 1H), 5.15 ꢀ 5.07 (m, 2H), 4.50 (t, J = 7.6 Hz, 1H), 3.94 (s, 3H), 3.88 (s, 3H), 2.82 ꢀ 2.75 (m,
1H), 2.64 ꢀ 2.58 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 194.1, 153.4, 149.0, 134.9, 134.4,
132.3, 129.1, 129.0, 128.6, 123.1, 117.7, 110.9, 110.0, 56.1, 55.9, 50.6, 35.5. HRMS (ESI)
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calculated [M+H] + for C19H21O3S: 329.1206, found: 329.1209. FTIR (cm-1) 3020, 1668, 1595,
1464, 1418, 1216, 1134, 1023.
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1-(3,4-Dichlorophenyl)-2-(phenylthio)pent-4-en-1-one (3p): (pale yellow oil, 0.090 g, 53%
yield). Rf (Pet. ether /EtOAc = 95/05): 0.30; 1H NMR (400 MHz, CDCl3) δ 7.97 (s, 1H), 7.75 (d,
J = 7.9 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.36 ꢀ 7.28 (m, 5H), 5.93ꢀ5.84 (m, 1H), 5.18 ꢀ 5.04 (m,
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2H), 4.37 (t, J = 7.1 Hz, 1H), 2.79 ꢀ 2.72 (m, 1H), 2.64 ꢀ 2.57 (m, 1H). C NMR (100 MHz,
CDCl3) δ 192.8, 137.6, 135.8, 135.2, 134.5, 133.3, 130.7, 130.7, 129.3, 129.2, 127.7, 118.2,
+
51.1, 34.8. HRMS (ESI) calculated [M+H] for C17H15OCl2S: 337.0215, found: 337.0209.
FTIR (cm-1) 3016, 1681, 1583, 1469, 1385, 1276, 1212, 1136, 1064, 1029.
1-(3-Bromo-4-fluorophenyl)-2-(phenylthio)pent-4-en-1-one (3q): (pale yellow oil, 0.110 g,
60% yield). Rf (Pet. ether /EtOAc = 95/05): 0.40; 1H NMR (400 MHz, CDCl3) δ 8.11 ꢀ 8.09 (m,
1H), 7.89 ꢀ 7.85 (m, 1H), 7.38 ꢀ 7.28 (m, 5H), 7.20 ꢀ 7.15 (m, 1H), 5.94 ꢀ 5.84 (m, 1H), 5.17 ꢀ
5.11 (m, 2H), 4.38 (t, J = 7.3 Hz, 1H), 2.80 ꢀ 2.72 (m, 1H), 2.64 ꢀ 2.57 (m, 1H). 13C NMR (100
MHz, CDCl3) δ 192.5, 162.0 (d, J = 256.2), 135.1, 134.6 (d, J = 4.2 Hz), 131.1, 129.9 (d, J = 8.5
Hz), 129.3, 129.2, 118.2, 116.7 (d, J = 22.9 Hz), 109.9, 109.7, 51.0, 34.9. HRMS (ESI)
+
calculated [M+H] for C17H15OBrFS: 365.0006, found: 365.0000. FTIR (cm-1) 3019, 1681,
1590, 1492, 1438, 1396, 1251, 1046.
2-Allyl-2-(phenylthio)-2,3-dihydro-1H-inden-1-one (3r): (colorless oil, 0.96 g, 68% yield). Rf
(Pet. ether /EtOAc = 95/05): 0.36; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.6 Hz, 1H), 7.56
(t, J = 7.4 Hz, 1H), 7.46 (d, J = 7.4 Hz, 2H), 7.40 – 7.33 (m, 3H), 7.28 (t, J = 7.4 Hz, 2H), 5.84 –
5.74 (m, 1H), 5.16 (dd, J1 = 19.9 Hz, J2 = 13.7 Hz, 2H), 3.42 (d, J = 17.9 Hz, 1H), 3.14 (d, J =
13
17.9 Hz, 1H), 2.67 (d, J = 7.0 Hz, 2H). C NMR (100 MHz, CDCl3) δ 202.2, 150.5, 137.2,
135.5, 135.0, 133.1, 130.2, 129.6, 128.6, 127.8, 126.2, 124.7, 119.4, 58.6, 39.4, 38.5. HRMS
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(ESI) calculated [M+H] + for C18H17OS: 281.0995, found: 281.1002. FTIR (cm-1) 3020, 2984,
1744, 1631, 1522, 1421, 1392, 1373, 1187, 1117, 927.
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2-Allyl-2-(phenylthio)-3,4-dihydronaphthalen-1(2H)-one (3s): (yellow oil, 0.098 g, 62%
yield). Rf (Pet. ether /EtOAc = 95/05): 0.36; 1H NMR (400 MHz, CDCl3) δ 8.15 (d, J = 7.8 Hz,
1H), 7.52 (t, J = 7.4 Hz, 1H), 7.42ꢀ7.26 (m, 7H), 5.96ꢀ5.85 (m, 1H), 5.17ꢀ5.13 (m, 2H), 3.52ꢀ3.43
(m, 1H), 2.94ꢀ2.89 (m, 1H), 2.70ꢀ2.65 (m, 1H), 2.58ꢀ2.53 (m, 1H), 2.48ꢀ2.40 (m, 1H), 2.30ꢀ2.25
(m, 1H). 13C NMR (100 MHz, CDCl3) δ 192.0, 142.5, 137.5, 133.8, 133.1, 131.6, 129.6, 129.2,
128.8, 128.6, 128.4, 126.8, 118.8, 57.5, 40.2, 32.3, 25.6. HRMS (ESI) calculated [M+H] + for
C19H19OS: 295.1151, found: 295.1154. FTIR (cm-1) 3019, 1674, 1638, 1601, 1474, 1430, 1355,
1308, 1218, 1126, 1044, 922, 772, 691, 669.
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2-Allyl-2-(phenylthio)cyclopentan-1-one (3t): (pale yellow oil, 0.090 g, 78% yield). Rf (Pet.
ether /EtOAc = 95/05): 0.18; 1H NMR (400 MHz, CDCl3) δ 7.46 ꢀ 7.28 (m, 5H), 5.86 ꢀ5.76 (m,
1H), 5.16 ꢀ 5.10 (m, 2H), 2.73 ꢀ 2.63 (m, 1H), 2.48 ꢀ 2.43 (m, 1H), 2.32 ꢀ 2.27 (m, 1H), 2.22 ꢀ
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2.07 (m, 3H), 2.03 ꢀ 1.90 (m, 2H). C NMR (100 MHz, CDCl3) δ 211.6, 137.3, 133.4, 129.9,
129.7, 128.8, 118.9, 59.6, 37.9, 36.0, 33.9, 18.0. HRMS (ESI) calculated [M+H] + for C14H17OS:
233.0995, found: 233.0996. FTIR (cm-1) 3018, 1727, 1639, 1523, 1473, 1319, 1215, 1165, 1068,
1002.
2-Allyl-2-(phenylthio)cyclohexan-1-one (3u): (yellow solid, 0.070 g, 57% yield). Rf (Pet. ether
/EtOAc = 95/05): 0.75; 1H NMR (400 MHz, CDCl3) δ 7.37 ꢀ 7.28 (m, 5H), 5.92 ꢀ5.82 (m, 1H),
5.14 ꢀ 5.04 (m, 2H), 3.44 ꢀ 3.35 (m, 1H), 2.37 ꢀ 2.32 (m, 3H), 2.16 ꢀ 2.07 (m, 3H), 1.98 ꢀ 1.91 (m,
1H), 1.27 ꢀ 1.64 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 207.2, 136.3, 134.0, 130.4, 129.5,
129.0, 118.5, 60.3, 39.8, 37.8, 36.8, 27.0, 21.3. HRMS (ESI) calculated [M+H] + for C15H19OS:
247.1151, found: 247.1153. FTIR (cm-1) 3018, 1698, 1474, 1316, 1291, 1149, 1122, 1025, 998.
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2-Allyl-2-(phenylthio)cycloheptan-1-one (3v):26 (pale yellow oil, 0.083 g, 64% yield). Rf (Pet.
ether /EtOAc = 95/05): 0.25; 1H NMR (400 MHz, CDCl3) δ 7.37 ꢀ 7.29 (m, 5H), 6.08 ꢀ5.98 (m,
1H), 5.17 ꢀ 5.06 (m, 2H), 3.26 ꢀ 3.21 (m, 1H), 2.49 ꢀ 2.39 (m, 2H), 2.27 ꢀ 2.18 (m, 2H), 1.97 ꢀ
1.83 (m, 3H), 1.61 ꢀ 1.55 (m, 1H), 1.44 ꢀ 1.40 (m, 2H), 1.23 ꢀ 1.18 (m, 1H). 13C NMR (100
MHz, CDCl3) δ 207.9, 136.7, 134.4, 130.6, 129.5, 128.9, 118.3, 62.4, 39.6, 36.3, 32.3, 30.4,
26.5, 24.5. HRMS (ESI) calculated [M+H] + for C16H21OS: 261.1308, found: 261.1310. FTIR
(cm-1) 3017, 1692, 1439, 1217, 1156, 1065, 1022, 921.
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4-Methyl-4-(phenylthio)hept-6-en-3-one (3w): (Colorless oil, 0.070 g, 60% yield). Rf (Pet.
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ether /EtOAc = 95/05): 0.42; H NMR (400 MHz, CDCl3) δ 7.31ꢀ7.29 (m, 5H), 5.82ꢀ5.73 (m,
1H), 5.15ꢀ5.11 (m, 2H), 2.83 (q, J = 7.2 Hz, 2H), 2.63ꢀ2.59 (m, 1H), 2.47ꢀ2.43 (m, 1H), 1.39 (s,
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3H), 1.14 (t, J = 7.3 Hz, 3H). C NMR (100 MHz, CDCl3) δ 208.09, 136.30, 133.32, 130.84,
129.40, 128.97, 119.01, 59.23, 41.30, 29.85, 21.30, 8.60. HRMS (ESI) calculated [M+H] + for
C14H19OS: 235.1151, found: 235.1150. FTIR (cm-1) 3018, 1700, 1473, 1457, 1414, 1376, 1216,
1083, 976, 754, 667.
2-((3,4-Dimethylphenyl)thio)-1-phenylpent-4-en-1-one (3x): (yellow oil, 0.094 g, 64% yield).
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Rf (Pet. ether /EtOAc = 95/05): 0.39; H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 7.9 Hz, 1H),
7.58ꢀ7.54 (m, 2H), 7.47ꢀ7.43 (m, 2H), 7.10ꢀ7.03 (m, 3H), 5.94ꢀ5.84 (m, 1H), 5.15ꢀ5.06 (m, 2H),
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4.44 (t, J = 7.3 Hz, 1H), 2.78ꢀ2.71 (m, 1H), 2.61ꢀ2.54 (m, 1H), 2.23 (s, 3H), 2.19 (s, 3H). C
NMR (100 MHz, CDCl3) δ 195.2, 138.0, 137.4, 136.5, 136.3, 135.1, 133.0, 132.8, 130.3, 128.7,
+
128.6, 127.7, 117.7, 50.9, 35.0, 19.7, 19.6. HRMS (ESI) calculated [M+H] for C19H21OS:
297.1308, found: 297.1318. FTIR (cm-1) 3081, 2924, 1678, 1640, 1597, 1580, 1485, 1448, 1383,
1344, 1217, 924, 814, 771, 687, 668.
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2-(Benzo[d][1,3]dioxol-5-ylthio)-1-phenylpent-4-en-1-one (3y): (colorless oil, 0.127 g, 81%
yield). Rf (Pet. ether /EtOAc = 70/30): 0.48; 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 7.7 Hz,
2H), 7.56 (t, J = 7.2 Hz, 1H), 7.45 (t, J = 7.5 Hz, 2H), 6.84 ꢀ 6.79 (m, 2H), 6.70 (d, J = 8.0 Hz,
1H), 5.96 (s, 2H), 5.93ꢀ5.82 (m, 1H), 5.11 (dd, J1 = 19.3 Hz, J1 = 13.8 Hz, 2H), 4.39 (t, J = 7.3
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Hz, 1H), 2.76 ꢀ 2.69 (m, 1H), 2.59 ꢀ 2.52(m, 1H). C NMR (100 MHz, CDCl3) δ 194.9, 149.0,
147.8, 136.2, 134.9, 133.1, 130.6, 128.7, 128.6, 122.5, 117.8, 115.9, 108.7, 101.6, 51.0, 34.7.
HRMS (ESI) calculated [M+H] + for C18H17O3S: 313.0893, found: 313.0888. FTIR (cm-1) 3011,
2935, 1745, 1600, 1505, 1422, 1350, 1185, 1026, 991, 770.
2-((3,4-Difluorophenyl)thio)-1-phenylpent-4-en-1-one (3z): (pale yellow oil, 0.084 g, 56%
yield). Rf (Pet. ether /EtOAc = 95/05): 0.39; 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 7.6 Hz,
2H), 7.60ꢀ7.56 (m, 1H), 7.48ꢀ7.45 (m, 2H), 7.16 (t, J = 8.7 Hz, 1H), 7.10ꢀ7.02 (m, 2H), 5.91ꢀ5.81
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(m, 1H), 5.16ꢀ5.09 (m, 2H), 4.48 (t, J = 7.5 Hz 1H), 2.77ꢀ2.70 (m, 1H), 2.59ꢀ2.52 (m, 1H). C
NMR(100 MHz, CDCl3) δ 194.8, 152.0 (J1= 14.2 Hz, J2 = 136.0 Hz), 150.1 (J1 = 14.0 Hz, J2 =
136.6 Hz), 135.9, 134.4, 133.5, 132.1 (t, J = 4.81 Hz), 128.8, 128.6, 127.2 (t, J = 4.6 Hz), 124.4
(dd, J1 = 3.7 Hz, J2 = 14.5 Hz), 118.2, 117.8 (dd, J1 = 7.9 Hz, J2 = 11.0 Hz), 50.7, 34.8. HRMS
(ESI) calculated [M+H] + for C17H15OF2S: 305.0806, found: 305.0805. FTIR (cm-1) 3019, 1678,
1597, 1525, 1483, 1423, 1217, 1045, 928, 669.
2-((2,5-Dimethylphenyl)thio)-1-phenylpent-4-en-1-one (3aa): (viscous yellow oil, 0.121 g,
82% yield). Rf (Pet. ether /EtOAc = 95/05): 0.23; 1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 7.6
Hz, 2H), 7.55 (t, J = 7.0 Hz, 1H), 7.40 (t, J = 7.2 Hz, 2H), 7.18 (s, 1H), 7.08 ꢀ 7.0 (m, 2H), 5.97ꢀ
5.87 (m, 1H), 5.18ꢀ5.09 (m, 2H), 4.56 – 4.53 (m, 1H), 2.93 – 2.86 (m, 1H), 2.72 ꢀ 2.65 (m, 1H),
2.28 (s, 3H), 2.26 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 196.1, 138.5, 136.4, 136.0, 135.5,
134.9, 133.1, 131.5, 130.4, 129.5, 128.5, 128.5, 117.8, 50.9, 35.6, 20.7, 20.5. HRMS (ESI)
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calculated [M+H] + for C19H21OS: 297.1308, found: 297.1302. FTIR (cm-1) 3060, 2855, 1679,
1649, 1379, 1276, 997, 812.
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2-((3-Methoxyphenyl)thio)-1-phenylpent-4-en-1-one (3ab): (yellow oil, 0.075 g, 50% yield).
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Rf (Pet. ether /EtOAc = 95/05): 0.23; H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 7.1 Hz, 2H),
7.58 (t,J = 7.3 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 7.21 (t, J = 7.8 Hz, 1H), 6.98 (d,J = 7.7 Hz,1H),
6.89 ꢀ 6.86 (m, 2H), 5.96 ꢀ 5.86 (m, 1H), 5.18 ꢀ 5.09 (m, 2H), 4.55 (t,J = 7.1 Hz,1H), 3.75 (s,
3H), 2.86 ꢀ 2.79 (m, 1H), 2.67 ꢀ 2.66 (m, 1H). 13C NMR (100 MHz, CDCl3)δ 195.4, 159.6,
136.1, 134.8, 133.2, 133.0, 129.8, 128.6, 126.5, 119.4, 117.9, 114.8, 55.3, 51.0, 35.2. HRMS
(ESI) calculated [M+H] + for C18H19O2S: 299.1100, found: 299.1109. FTIR (cm-1) 3018, 1678,
1590, 1479, 1446, 1343, 1309, 1281, 1215, 1183, 996, 924, 777.
1-Phenyl-2-(m-tolylthio)pent-4-en-1-one (3ac) and 1-Phenyl-2-(p-tolylthio)pent-4-en-1-one
(3ac’): (viscous yellow oil, 0.101 g, 72% yield). The regioisomeric ratio was determined by GC
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analysis of the cude reaction mixture is (1:1). Rf (Pet. ether /EtOAc = 95/05): 0.23; H NMR
(400 MHz, CDCl3) δ 7.95 (t, J = 8.8 Hz, 2H), 7.58 ꢀ 7.44 (m, 3H), 7.26 (d, J = 8.1 Hz, 1H), 7.19
ꢀ 7.10 (m, 3H), 5.96 ꢀ 5.85 (m, 1H), 5.17 ꢀ5.09 (m, 2H), 4.52 (t, J = 7.2 Hz, 1H), 2.84 ꢀ 2.71 (m,
1H), 2.65 ꢀ 2.55 (m, 1H), 2.31 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 195.4, 138.8, 136.3,
135.5, 135.0, 133.1, 131.7, 129.0, 128.9, 117.8, 51.0, 35.2, 21.3. Representative peak for other
isomer: H NMR (400 MHz, CDCl3) δ 4.46 (t, J = 7.1 Hz), 2.35 (s). 13C NMR (100 MHz,
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CDCl3) δ 195.1, 139.3, 136.2, 135.4, 135.0, 133.1, 131.4, 129.7, 128.7, 117.7, 50.8, 34.9, 21.3.
HRMS (ESI) calculated [M+H] + for C18H19OS: 283.1151, found: 283.1154. FTIR (cm-1) 3018,
1678, 1580, 1475, 1344, 1275, 1181, 1000, 923.
2-((4-Fluorophenyl)thio)-1-phenylpent-4-en-1-one (3ad) and 2-((3-Fluorophenyl)thio)-1-
phenylpent-4-en-1-one (3ad’): (pale yellow oil, 0.102 g, 71% yield). The regioisomeric ratio
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determined by H NMR analysis of the crude reaction mixture (2.6:1). Rf (Pet. ether /EtOAc =
95/05): 0.25; 1H NMR (400 MHz, CDCl3) of major isomer δ 7.95 (d, J = 7.1 Hz, 2H), 7.59 (t, J
= 7.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H), 7.35 ꢀ 7.25 (m, 1H), 7.15 – 7.10 (m, 1H), 7.02 6.97 (m,
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2H), 5.93 ꢀ 5.84 (m, 1H), 5.17 ꢀ 5.10 (m, 2H), 4.46 (t, J = 7.2 Hz, 1H), 2.85 ꢀ 2.53 (m, 2H). C
NMR (100 MHz, CDCl3) of major isomer δ 194.9, 163.6 (d, J = 246.9 Hz), 137.8 (d, J = 8.8
Hz), 134.7, 134.5, 133.4, 133.2, 128.6, 117.9, 116.2 (d, J = 21.8 Hz), 50.7, 34.8. Representative
peak for minor isomer: H NMR (400 MHz, CDCl3) of minor isomer δ 4.57 (t, J = 7.4 Hz). 13C
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NMR (100 MHz, CDCl3) of minor isomer δ 195.2, 136.1, 136.0, 130.3 (d, J = 8.4 Hz), 130.0
(d, J = 3.1 Hz,), 128.7, 121.0 (d, J = 23.1 Hz), 118.1, 115.8 (d, J = 20.7 Hz), 50.9, 35.2. HRMS
(ESI) calculated [M+H] + for C17H16OFS: 287.0900, found: 287.0901. FTIR (cm-1) 3023, 1678,
1590, 1489, 1447, 1432, 1343, 1222, 921.
1,4-Diphenyl-2-(phenylthio)pent-4-en-1-one (3ae):25 (yellow solid, 0.073 g, 42% yield). The
regioisomeric ratio determined by 1H NMR analysis of the crude reaction mixture (2:1). Rf (Pet.
ether /EtOAc = 95/05): 0.30; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 7.7 Hz, 2H), 7.37ꢀ7.25
(m, 10H), 7.12ꢀ7.04 (m, 3H), 6.47ꢀ6.38 (m, 1H), 5.02ꢀ4.84 (m, 3H), 4.08ꢀ4.03 (m, 1H). 13C
NMR (100 MHz, CDCl3) δ 194.5, 141.7, 139.1, 136.7, 135.0, 132.8, 132.0, 129.0, 128.8, 128.6,
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128.5, 128.2, 126.8, 117.7, 56.2, 50.1. Representative peak for minor isomer: H NMR (400
MHz, CDCl3) δ 7.95 (d, J = 7.6 Hz), 7.57 (t, J = 7.5 Hz), 7.51ꢀ7.40 (m), 7.21ꢀ7.16 (m), 6.04ꢀ
5.96 (m), 5.34ꢀ5.18 (m), 4.14ꢀ4.11 (m). 13C NMR (100 MHz, CDCl3) δ 195.4, 140.5, 138.6,
136.9, 133.1, 132.3, 129.1, 128.9, 128.7, 128.5, 128.0, 127.1, 117.0, 56.4, 50.7. HRMS (ESI)
calculated [M+H] + for C23H21OS: 345.1308, found: 345.1320. FTIR (cm-1) 3027, 1678, 1597,
1580, 1474, 1449, 1268, 1215, 1183, 1025, 921, 753.
Procedure for the Product Functionalization
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Ozonolysis Reaction: A solution of 1ꢀphenylꢀ2ꢀ(phenylthio)pentꢀ4ꢀenꢀ1ꢀones 3a (1.5 mmol) in
30 mL of CH2Cl2 was stirred at −78 °C as ozone was passed through the solution. After 5ꢀ10
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min, the colorless reaction mixture changed to blue in color. Once blue color observed oxygen
was passed to remove excess of ozone until reaction mixture was become colorless. Then to the
reaction mixture dimethyl sulfide (15 ml) was added and continued the stirring at ꢀ78 °C for
another 20 min. Then the reaction mixture was allowed to warm up to room temperature, and
then continued stirring for another 12 h. The solvent was removed under reduced pressure.
Purification of the crude material on a silica gel column chromatography ethyl acetate and pet
ether afforded desired product 4 as yellow oil (350mg, 86%).
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4-Oxo-4-phenyl-3-(phenylthio)butanal (4):27 (viscous yellow oil, 350mg, 86%). Rf (Pet. ether
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/EtOAc = 90/10): 0.25; H NMR (400 MHz, CDCl3) δ 9.77 (s, 1H), 8.01 (d, J = 7.2 Hz, 2H),
7.61ꢀ7.29 (m, 8H), 4.98ꢀ4.95 (m, 1H), 3.57ꢀ3.30 (m, 1H), 3.03ꢀ2.97 (m, 1H). 13C NMR (100
MHz, CDCl3) δ 199.3, 194.3, 135.5, 135.3, 133.3, 130.4, 129.4, 129.2, 128.8, 128.6, 45.4, 44.4.
HRMS (ESI) calculated [M+H] + for C16H15O2S: 271.0787, found: 271.0785. FTIR (cm-1) 3019,
2852, 1720, 1680, 1597, 1474, 1439, 1399, 1352, 1216, 1069, 972, 771.
Procedure for the Synthesis of Disubstituted Furan: To a stirred suspension of 1,4ꢀdicarbonyl
compound 4 (0.25 mmol, 68.0 mg) in 4.0 mL of Ac2O at 0 °C, 1.0 mL con. HCl was added in
dropwise under Argon protection. After the vigorous reaction, the reaction mixture was allowed
to warm up to room temperature, and kept stirring for 3 h. The solvent was removed under
reduced pressure. Purification of the crude material on a silica gel column chromatography ethyl
acetate and pet ether afforded desired furan derivative 5 as yellow oil (50mg, 79%).
2-Phenyl-3-(phenylthio)furan (5):28 (viscous yellow oil, 50mg, 79%). Rf (Pet. ether /EtOAc =
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95/05): 0.63; H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 7.8 Hz, 2H), 7.56 (s, 1H), 7.44 (t, J =
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7.5 Hz, 2H), 7.37ꢀ7.35 (m, 1H), 7.30ꢀ7.28 (m, 4H), 7.21ꢀ7.19 (m, 1H), 6.51 (s, 1H). C NMR
(100 MHz, CDCl3) δ 154.6, 141.9, 137.0, 130.1, 129.1, 128.6, 128.3, 127.2, 126.1, 125.8, 117.7,
109.4. HRMS (ESI) calculated [M+H] + for C16H13OS: 253.0682, found: 253.0692. FTIR (cm-1)
3064, 3015, 2926, 2854, 1670, 1582, 1513, 1478, 1216, 1146, 1082, 1025, 885, 770.
Procedure for the Synthesis of Disubstituted Pyrrole: The mixture of 4ꢀoxoꢀ4ꢀphenylꢀ3ꢀ
(phenylthio)butanal 4 (0.25 mmol, 68.0 mg), ammonium acetate (1.25 mmol, 96.0 mg) and
MeOH/H2O (12:3 mL) was stirred for 3h at room temperature. Then the reaction mixture was
diluted with water and extracted with CH2Cl2. The organic layer was dried over Na2SO4, and the
solvent was removed under reduced pressure. Purification of the crude material on a silica gel
column chromatography ethyl acetate and pet ether afforded desired pyrrole derivative 6 as
yellow oil (51mg, 81%).
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2-Phenyl-3-(phenylthio)-1H-pyrrole (6):27 (dark brown oil, 51mg, 81%). Rf (Pet. ether /EtOAc
= 90/10): 0.28; 1H NMR (400 MHz, CDCl3) δ 8.56 (bs, 1H), 7.63 (d, J = 7.4 Hz, 2H), 7.40 (t, J
= 7.5 Hz, 2H), 7.33ꢀ7.10 (m, 6H), 6.94ꢀ6.93 (m, 1H), 6.45 (m, 1H). 13C NMR (100 MHz,
CDCl3) δ 140.4, 135.6, 131.8, 128.8, 128.7, 127.5, 127.0, 125.7, 124.6, 118.7, 117.2, 105.9.
HRMS (ESI) calculated [M+H] + for C16H14NS: 252.0841, found: 252.0840. FTIR (cm-1) 3461,
3019, 2927, 2854, 1659, 1603, 1582, 1496, 1441, 1216, 1081, 1025, 770.
Procedure for the Synthesis of Disubstituted Pyridazine: The dicarbonyl compound 4(0.25
mmol, 68.0 mg)was dissolved in ethanol (15mL) and hydrazine hydrate (1.25mmol, 63.0 mg)
was added. Thereaction mixture was refluxed at 80°C for 6h. The solvent was removed under
reduced pressure. Purification of the crude material on a silica gel column chromatography ethyl
acetate and pet ether afforded desired pyridazinederivative 7as white solid (33mg, 85%).
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3-Phenylpyridazine (7): 29 (white solid, 33mg, 85%). Rf (Pet. ether /EtOAc = 50/50): 0.38; H
NMR (400 MHz, CDCl3) δ 9.18ꢀ9.17 (m, 1H), 8.11 (d, J = 6.4 Hz, 2H), 7.89 (d, J = 8.6 Hz,
1H), 7.57ꢀ7.53 (m, 4H). 13C NMR (100 MHz, CDCl3) δ 159.6, 150.1, 136.4, 130.2, 129.1,
127.2, 126.9, 124.0. HRMS (ESI) calculated [M+H] + for C10H9N2: 157.0760, found: 157.0762.
FTIR (cm-1) 3011, 1727, 1658, 1580, 1547, 1452, 1432, 1374, 1297, 1217, 1099, 1028, 821.
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Supporting Information
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Copies of H and C NMR spectra of all products. This material is available free of charge via
the Internet at http://pubs.acs.org.
Acknowledgement
Generous financial support by Science and Engineering Research Board (SERBꢀDST),
Government of India (Grant No. SR/S1/OC/12/2012) is kindly acknowledged. M. T. thanks
CSIR for the fellowship, R. N. G. thanks UGC for the scholarship, and T.R. acknowledges DST
for the Inspire fellowship. We thank Dr. P. R. Rajamohanan (CSIRꢀNCL) for the excellent NMR
support and Dr. B. Santhakumari (CSIRꢀNCL) for the HRMS data.
References
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Sulfur-Containing Drugs and Related Organic Compounds: Chemistry, Biochemistry, And
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