Metal-free difunctionalization of alkynes with 2-chlorodithiane for synthesis of β-ketodithianes

Article abstract of DOI:10.1021/acs.joc.5b00187

Dithianes are versatile umpolung intermediates in organic synthesis but have rarely been employed in radical cross-coupling reactions. Here we describe the oxidative coupling method for alkyne difunctionalization under metal-catalyst-free conditions. The efficient protocol directly affords a variety of β-ketodithianes in good to excellent yields with high regioselectivities. It provides a general pathway for accessing valuable dithianes with controlled formation of a new C-C bond and a C-O bond via a radical coupling pathway.

Full text of DOI:10.1021/acs.joc.5b00187

Note
pubs.acs.org/joc
Metal-Free Difunctionalization of Alkynes with 2‑Chlorodithiane for
Synthesis of β‑Ketodithianes
Junshan Lai,† Lixia Tian,† Xing Huo,† Yuan Zhang,‡ Xingang Xie,‡ and Shouchu Tang*,†,‡
‡
†School of Pharmacy and State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, People’s
Republic of China
S
* Supporting Information
ABSTRACT: Dithianes are versatile umpolung intermediates
in organic synthesis but have rarely been employed in radical
cross-coupling reactions. Here we describe the oxidative
coupling method for alkyne difunctionalization under metal-
catalyst-free conditions. The efficient protocol directly affords
a variety of β-ketodithianes in good to excellent yields with
high regioselectivities. It provides a general pathway for accessing valuable dithianes with controlled formation of a new C−C
bond and a C−O bond via a radical coupling pathway.
1).5 More recently, Lipshutz6 and Loh7 independently
adical addition of unactivated alkynes is believed to be the
Rmost convenient procedure to generate reactive vinyl developed this ROC of aryl alkynes using a hydrocarbon
nanomicelle (eq 2) and DMSO (eq 3) in a number of C−S
bond-forming transformations. Despite the remarkable exten-
sions and developments of alkyne difunctionalization, the
discovery of new atom-economical protocols toward advanced
intermediates is still highly worthwhile.
radicals, which could be trapped via subsequent transformation
and thus appear in many diverse applications in organic
chemistry.1 Among various strategies for alkyne difunctionaliza-
tion, radical oxidative coupling (ROC)2 reactions have played
important roles in synthetic organic chemistry for bond
formations, and those processes can offer many complementary
methods to efficiently increase molecular complexity (Scheme
1). Recently, several remarkable advances of ROC catalyzed by
nonprecious metals (Fe, Cu, Ni) and metal-catalyst-free mild
conditions for bond construction in the presence of a green
oxidant such as oxygen have been developed.3−7 In particular,
Lei and co-workers elegantly reported a pioneering metal-
catalyst-free aerobic oxysulfonylation of terminal alkynes (eq
Dithiane compounds serve as valuable synthetic intermedi-
ates (umpolung synthons) in the field of natural product
synthesis and can participate in a range of useful trans-
formations.8 However, dithiane anion chemistry applied in
various synthetic sequences requires either lithiation or the use
of anhydrous and anaerobic technology.8a,b Access to β-
ketodithianes by radical cross-coupling would have advantages
over traditional dithiane anion strategies, and the ability to form
dithiane derivatives directly would improve the efficiency of
synthetic routes. In this regard, our group has a long-standing
interest in the novel and versatile protocols to construct
dithiane derivatives.9 Recently, our group introduced the first
protocol for the direct cross-coupling of alkene involving a
novel dithianyl radical coupling mechanism.9a,c On this basis,
we postulated that an oxidative dithiane radical strategy10 could
serve as a platform for the difunctionalization of unactivated
alkynes (Scheme 1, eq 4). Mechanistically, we expected that
radical addition of alkyne with the dithianyl radical should give
the dithiane vinyl radical intermediate, where subsequent
interaction with molecular oxygen would be highly favored
and ultimately lead to β-ketodithiane, which is known to be a
key intermediate for useful transformations.11 To the best of
our knowledge, the alkyne difunctionalization with a dithianyl
radical for tandem C−C and C−O bond formations has not yet
been reported. In this paper, we report our recent progress on
the first metal-free oxidative coupling protocol for alkyne
Scheme 1. Novel Strategies for Alkyne Difunctionalization
Received: January 27, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00187
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a b
,
difunctionalization to give β-ketodithianes, which affords a
marked improvement over functionalization with anion-
initiated dithiane chemistry developed previously.8,12
Table 2. Substrate Scope of Alkyne Difunctionalization
We began our study via a model reaction to investigate the
coupling reaction of phenylacetylene 1a with easily accessible 2-
chlorodithiane 2 (Table 1). To identify conditions for the
Table 1. Reaction Conditions for the Coupling of
a
Phenylacetylene
b
entry
acid (equiv)
time (h)
3a (%)
1
2
3
4
48
48
24
24
24
24
6
trace
trace
12
FeCl3 (0.15)
FeCl3 (1.2)
BF3·Et2O (0.15)
FeCl3·6H2O (0.15)
FeCl2·4H2O (0.15)
MsOH (1.2)
12
b
5
18
b
6
32
7
8
79
TsOH (1.2)
12
24
24
24
65
9
H2SO4 (1.2)
trace
trace
trace
c
10
11
HCl (1.2)
MsOH (0.15)
a
Reaction conditions: phenylacetylene (1a, 0.225 mmol), 2-chloro-
1,3-dithiane (2, 0.25 mmol), acid (x equiv), DCE (2 mL), 50 °C, air,
b
c
6−48 h. Isolated yields. 12 mol/L.
coupling reaction, we hypothesized that the factors that
influence the reactivity of the reaction would exhibit a
dependence on various parameters, such as metal sources,
acids, solvents, and reaction temperature. Initially, the coupling
of 1a with 2 employing Lewis acid sources such as FeCl3, FeCl2,
FeCl3·6H2O, and BF3·Et2O gave 3a, albeit in low yields.
However, these results indicated that the process involving the
C−C coupling and the subsequent transformation was indeed
possible (Table 1, entries 1−6). A number of commercially
available protic acids was examined. To our delight, further
optimization showed that the combination of a stoichiometric
amount of methanesulfonic acid (MsOH) at 50 °C under an
atmosphere of air5−7,13 served as the best condition, providing a
good yield of β-ketodithiane product 3a (Table 1, entry 7). It is
important to note that when the reactions were employed by
Lei and Loh’s reaction systems,5,7 the reactions were
unsuccessful and trace amounts of product 3a were obtained.
With optimized reaction conditions established (Table 1,
entry 7), we next turned our attention to a variety of aryl and
aliphatic alkynes that can participate in this novel process. As
shown in Table 2, the standard reaction system using 1.2 equiv
of MsOH in the presence of air was highly effective with
terminal aryl alkynes, affording the desired β-ketodithiane
products 3a−3n in moderate to good yields and excellent
chemoselectivities. Substrates with ortho (1j−1l), meta (1h),
and para (1b−1g) substituents provided good yields of coupled
products regardless of the electronic nature of the substituents.
Furthermore, the internal alkynes ranging from aryl to aliphatic
substituents (1o, 1p, 1r−1t) could also be effectively coupled in
12 h, although the steric crowding of alkynes lowered the yield
slightly. For example, using 2 equiv of MsOH in DCE for 12−
a
Reaction conditions: alkynes (1a−1t, 0.225 mmol), 2-chloro-1,3-
dithiane (2, 0.25 mmol), MsOH (1.2 equiv), DCE (2 mL), 50 °C, air,
b
c
4−48 h. Isolated yield after column chromatography. 17% 1q
d
e
recovery. 2 equiv of MsOH was used. Regioselectivities by 1H NMR
(>95:5).
24 h at 50 °C, the hindered 1,2-diarylalkynes 1r−1t afforded
the desired products 3r−3t and high regioselectivities (>95:5)
for 3s and 3t, as determined by 1H NMR analysis. Importantly,
1-heptyne also proved to be a suitable substrate and gave the
corresponding dithiane 3q in satisfactory yield based on the
recovered starting material.
In order to aid our interpretation of the mechanism, radical-
trapping experiments were conducted. The addition of 2,2,6,6-
tetramethyl-1-piperidinyloxy (TEMPO)14 and butylated hy-
droxytoluene (BHT)15 as radical scavenger under the standard
reaction conditions completely quenched the coupling reaction
and provided trace cross-coupled product, demonstrating that a
radical process might take place (Scheme 2). Meanwhile, we
also performed oxygen-labeling experiments to understand the
origin of the new C−O bond in the target molecule. In the
presence of H218O/air, product 3a was obtained in 72% yield
B
DOI: 10.1021/acs.joc.5b00187
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Scheme 2. Radical-Trapping Experiments and H218O Isotope
Labeling Experiment
without the requirement of organolithium reagents or metal
catalysts.
EXPERIMENTAL SECTION
■
General Information. Flash chromatography columns were
generally performed on silica gel (200−300 mesh) in petroleum (bp
60−90 °C), and reactions were monitored by thin layer chromatog-
raphy (TLC) using silica gel GF254 plates with UV light to visualize
the course of the reaction. All new compounds were characterized by
1H NMR, 13C NMR, IR, MS, and HRMS. H and 13C NMR spectra
1
were run with tetramethylsilane as an internal standard at 300 and 75
MHz, respectively. All chemical shifts (δ) are reported in parts per
million and coupling constants (J) in hertz. IR spectra were obtained
with neat thin films on a sodium chloride disk and were recorded on
an Fourier transform infrared spectrometer.
Materials. Analytical grade solvents and commercially available
reagents were used as received. Unless otherwise noted, materials were
obtained from commercial suppliers and used without further
purification. Alkynes 1a−e, 1n, and 1q−1t were purchased and used
as received. 2-Chloro-1,3-dithiane 2 and alkynes 1f−1m, 1o, and 1p
were prepared according to the reported procedure.18,19
General Procedure for the Alkyne Difunctionalization. To a
flame-dried 10 mL flask were added 2-chloro-1,3-dithiane 2 (34 mg,
0.25 mmol), 1a−1t (0.225 mmol), and methanesulfonic acid (1.2−2.0
equiv) in 2 mL of DCE. The reaction mixture was stirred at 50 °C for
4−24 h and then cooled to rt. The reaction solution was diluted with
ethyl acetate (5 mL) and saturated aqueous NaHCO3 (5 mL). The
organic layer was separated, and the aqueous phase was re-extracted
with ethyl acetate (3 × 3 mL). The combined organic extracts were
washed with brine (10 mL) and dried over anhydrous Na2SO4. The
solvent was concentrated under reduced pressure and purified by
column chromatography on silica gel with petroleum/ethyl acetate
(EA/PE = 1:50) to yield products 3a−3t.
Radical-Trapping Experiments. To a flame-dried 10 mL flask
were added 2-chloro-1,3-dithiane 2 (34 mg, 0.25 mmol), 1a (25 mg,
0.25 mmol), methanesulfonic acid (25 mg, 0.25 mmol), and TEMPO
(150 mg, 0.75 mmol) or BHT (165 mg, 0.75 mmol) in 2 mL of DCE.
The reaction mixture was stirred at 50 °C for 24 h. The reaction
mixture was diluted with ethyl acetate (10 mL) and H2O (5 mL). The
organic layer was separated, and the aqueous phase was re-extracted
with ethyl acetate (3 × 3 mL). The combined organic extracts were
washed with H2O (10 mL) and dried over anhydrous Na2SO4.
H218O-Labeling Experiment. To a flame-dried 10 mL flask were
added methanesulfonic acid (25 mg, 0.25 mmol) and H218O (7 mg,
0.38 mmol) in 2 mL of DCE and stirred for a while (methanesulfonic
acid and DCE in this experiment had been dried), then 2-chloro-1,3-
dithiane 2 (34 mg, 0.25 mmol) and 1a (25 mg, 0.25 mmol) were
added. The reaction mixture was stirred at 50 °C for 6 h. The reaction
solution was diluted with ethyl acetate (5 mL) and saturated aqueous
NaHCO3 (5 mL). The organic layer was separated, and the aqueous
and no isotope-labeled product was formed. The 18O-labeling
result suggested that water was not involved in the reaction
process,16 and the oxygen molecule was the possible source of
the carbonyl oxygen atom of the β-ketodithiane.5,6,13
On the basis of previous works in our group,9 we anticipated
that the dithianyl radical was generated via the homolysis of 2-
chlorodithiane under air and heating. The generated dithianyl
radical would be highly nucleophilic and thereby readily
facilitate conjugate addition with alkyne to forge a new C−C
bond with concomitant formation of the vinyl radical
intermediate (II). Subsequently, the generated vinyl radical
species are further oxidized by air to give a peroxyl radical (III),
which may stabilize to a hydroperoxide intermediate (IV) by
hydrogen abstraction from DCE.17 The hydroperoxide could
undergo heterolysis to generate enol intermediate (V), thus
completing the ROC reaction to form the desired β-
ketodithiane. It was worthy to note that one possible difficulty
may be the issue of C−O versus C−Cl bond formation;
however, the appropriate choice of acid can block the C−Cl
bond formation toward the desired β-keto product (Scheme 3).
In summary, we have described the direct alkyne
difunctionalization for the efficient construction of β-
ketodithianes. We have demonstrated that the versatile method
tolerates broad substrate scope and good functional group
compatibility. More importantly, this novel process provides an
alternative to generate highly substituted dithiane derivatives
Scheme 3. Proposed Mechanism
C
DOI: 10.1021/acs.joc.5b00187
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
phase was re-extracted with ethyl acetate (3 × 3 mL). The combined
organic extracts were washed with brine (10 mL) and dried over
anhydrous Na2SO4. The solvent was concentrated under reduced
pressure and purified by column chromatography on silica gel with
petroleum/ethyl acetate (EA/PE = 1:50) to yield the product 3a.
2-(1,3-Dithian-2-yl)-1-phenylethanone (3a): White solid; Rf = 0.47
2.86 (m, 2H), 2.85−2.75 (m, 2H), 2.14−2.00 (m, 1H), 1.91−1.77 (m,
1H); 13C NMR (75 MHz, CDCl3) δ 194.2, 150.4, 140.8, 129.2, 123.9,
44.4, 41.2, 30.2, 29.6, 25.1; IR (neat, cm−1) 3109 (w), 2975 (m), 2905
(m), 1694 (s), 1599 (w), 1519 (s), 1339 (s), 1215 (m), 1053 (m), 980
(w), 854 (m), 751 (m), 671 (w), 554 (w), 504 (w); MS (EI, 70 eV)
m/z = 283 (M+); HRMS (ESI) m/z [M + Na]+ (C12H13NO3S2Na)
calcd 306.0235, found 306.0239.
1
(EA/PE = 1:10); mp (°C) 58−59; isolated yield 79% (42 mg); H
NMR (300 MHz, CDCl3) δ 8.04−7.87 (m, 2H), 7.62−7.55 (m, 1H),
7.55−7.40 (m, 2H), 4.70 (t, J = 6.7 Hz, 1H), 3.36 (d, J = 6.8 Hz, 2H),
3.03−2.94 (m, 2H), 2.94−2.82 (m, 2H), 2.17−2.08 (m, 1H), 1.97−
1.83 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 195.0, 136.1, 133.1,
128.3, 127.8, 43.5, 41.1, 29.8, 24.9; MS (EI, 70 eV) m/z = 238 (M+).
This known compound had been characterized previously.20
2-(1,3-Dithian-2-yl)-1-(p-tolyl)ethanone (3b): White solid; Rf =
0.49 (EA/PE = 1:10); mp (°C) 105−106; isolated yield 76% (43 mg);
1H NMR (300 MHz, CDCl3) δ 7.87 (d, J = 9 Hz, 2H), 7.27 (d, J = 9
Hz, 2H), 4.69 (t, J = 6.9 Hz, 1H), 3.33 (d, J = 6.9 Hz, 2H), 2.97 (t, J =
14.2, 2H), 2.85 (t, J = 14.2 Hz, 2H), 2.41 (s, 3H), 2.21−2.05 (m, 1H),
1.94−1.82 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 194.4, 143.7,
133.5, 128.8, 128.4, 127.8, 43.2, 41.2, 29.7, 24.8, 21.2; IR (neat, cm−1)
2920 (w), 2890 (w), 1688 (s), 1606 (m), 1412 (m), 1344 (m), 1227
(m), 1180 (m), 1043 (m), 978 (m), 818 (m), 724 (w), 679 (w), 589
(m), 559 (m); MS (EI, 70 eV) m/z = 252 (M+); HRMS (ESI) m/z
[M + Na]+ (C13H16OS2Na) calcd 275.0540, found 275.0542.
1-(3-Bromophenyl)-2-(1,3-dithian-2-yl)ethanone (3h): White
solid; Rf = 0.37 (EA/PE = 1:10); mp (°C) 116−117; isolated yield
69% (49 mg); 1H NMR (300 MHz, CDCl3) δ 8.09 (s, 1H), 7.89 (d, J
= 7.8 Hz, 1H), 7.69 (d, J = 7.9 Hz, 1H), 7.38 (t, J = 7.9 Hz, 1H), 4.69
(t, J = 6.8 Hz, 1H), 3.37 (d, J = 6.9 Hz, 2H), 3.03−2.93 (m, 2H),
2.91−2.76 (m, 2H), 2.19−2.07 (m, 1H), 1.98−1.81 (m, 1H); 13C
NMR (75 MHz, CDCl3) δ 193.9, 137.9, 136.0, 130.9, 130.0, 126.5,
122.8, 43.7, 41.1, 29.9, 25.0; IR (neat, cm−1) 3077 (w), 2935 (w), 2890
(w), 1686 (s), 1561 (m), 1419 (s), 1344 (m), 1275 (m), 1215 (s),
1065 (w), 898 (m), 798 (s), 706 (m), 684 (m), 619 (m), 447 (m); MS
(EI, 70 eV) m/z = 318 (M+); HRMS (ESI) m/z [M + Na]+
(C12H13BrOS2Na) calcd 338.9489, found 338.9493.
2-(1,3-Dithian-2-yl)-1-(o-tolyl)ethanone (3i): White solid; Rf =
0.45 (EA/PE = 1:10); mp (°C) 84−85; isolated yield 76% (43 mg);
1H NMR (300 MHz, CDCl3) δ 7.62 (d, J = 7.7 Hz, 1H), 7.38 (t, J =
7.6 Hz, 1H), 7.27 (d, J = 15.3 Hz, 2H), 4.63 (t, J = 7.0 Hz, 1H), 3.30
(d, J = 7.0 Hz, 2H), 2.95−2.85 (m, 4H), 2.51 (s, 3H), 2.14−2.03 (m,
1H), 1.93−1.82 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 199.0, 138.4,
137.0, 131.9, 131.5, 128.3, 125.6, 46.5, 41.6, 29.9, 25.1, 21.2; IR (neat,
cm−1) 3062 (w), 2977 (w), 2895 (w), 1683 (m), 1459 (m), 1409 (m),
1272 (m), 1220 (m), 1170 (m), 1048 (s), 973 (m), 881 (m), 766 (m),
724 (m), 629 (m), 462 (m); MS (EI, 70 eV) m/z = 252 (M+); HRMS
(ESI) m/z [M + Na]+ (C13H16OS2Na) calcd 275.0540, found
275.0542.
2-(1,3-Dithian-2-yl)-1-(2-methoxyphenyl)ethanone (3j): Yellow
oil; Rf = 0.40 (EA/PE = 1:10); isolated yield 78% (47 mg); 1H
NMR (300 MHz, CDCl3) δ 7.74 (dd, J = 7.7, 1.8 Hz, 1H), 7.58−7.42
(m, 1H), 7.08−6.85 (m, 2H), 4.69 (t, J = 6.9 Hz, 1H), 3.91 (s, 3H),
3.41 (d, J = 6.9 Hz, 2H), 3.00−2.90 (m, 2H), 2.89−2.78 (m, 2H),
2.16−2.04 (m, 1H), 1.92−1.80 (m, 1H); 13C NMR (75 MHz, CDCl3)
δ 197.2, 158.6, 133.9, 130.6, 127.3, 120.6, 111.4, 55.4, 48.9, 41.7, 30.1,
25.3; IR (neat, cm−1) 3072 (w), 2942 (w), 2908 (w), 2828 (w), 1671
(s), 1596 (s), 1481 (s), 1457 (m), 1432 (m), 1282 (s), 1247 (s), 1160
(m), 1028 (m), 980 (w), 936 (w), 911 (w), 763 (s), 621 (m); MS (EI,
70 eV) m/z = 268 (M+); HRMS (ESI) m/z [M + Na]+
(C13H16O2S2Na) calcd 291.0489, found 291.0493.
2-(1,3-Dithian-2-yl)-1-(4-methoxyphenyl)ethanone (3c): Yellow
solid; Rf = 0.42 (EA/PE = 1:10); mp (°C) 75−76; isolated yield
1
80% (48 mg); H NMR (300 MHz, CDCl3) δ 7.93 (d, J = 8.7 Hz,
2H), 6.92 (d, J = 8.7 Hz, 2H), 4.67 (t, J = 6.9 Hz, 1H), 3.83 (s, 3H),
3.29 (d, J = 6.9 Hz, 2H), 2.94 (t, J = 12.5 Hz, 2H), 2.88−2.74 (m, 2H),
2.15−2.03 (m, 1H), 1.91−1.79 (m, 1H); 13C NMR (75 MHz, CDCl3)
δ 193.5, 163.4, 130.1, 129.2, 113.5, 55.2, 43.1, 41.5, 29.9, 25.0; MS (EI,
70 eV) m/z = 268 (M+). This known compound had been
characterized previously.21
2-(1,3-Dithian-2-yl)-1-(4-fluorophenyl)ethanone (3d): White
solid; Rf = 0.45 (EA/PE = 1:10); mp (°C) 88−89; isolated yield
1
75% (43 mg); H NMR (300 MHz, CDCl3) δ 8.16−7.88 (m, 2H),
7.27−6.97 (m, 2H), 4.68 (t, J = 6.8 Hz, 1H), 3.33 (d, J = 6.9 Hz, 2H),
3.03−2.92 (m, 2H), 2.90−2.82 (m, 2H), 2.18−2.08 (m, 1H), 1.95−
1.84 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 193.7, 167.4, 164.0,
130.8, 130.6, 115.8, 115.5, 43.6, 41.4, 30.1, 25.1; IR (neat, cm−1) 3072
(w), 2977 (w), 2903 (w), 1688 (m), 1599 (m), 1506 (m), 1402 (m),
1352 (m), 1220 (m), 1093 (m), 1050 (m), 980 (m), 841 (m), 584
(m), 562 (m); MS (EI, 70 eV) m/z = 256 (M+); HRMS (ESI) m/z
[M + Na]+ (C12H13FOS2Na) calcd 279.0290, found 279.0293.
1-(4-Chlorophenyl)-2-(1,3-dithian-2-yl)ethanone (3e): White
solid; Rf = 0.45 (EA/PE = 1:10); mp (°C) 97−98; isolated yield
1-(2-Bromophenyl)-2-(1,3-dithian-2-yl)ethanone (3k): White
solid; Rf = 0.45 (EA/PE = 1:10); mp (°C) 71−72; isolated yield
1
69% (49 mg); H NMR (300 MHz, CDCl3) δ 7.69−7.56 (m, 1H),
1
73% (45 mg); H NMR (300 MHz, CDCl3) δ 7.89 (d, J = 8.9 Hz,
7.49−7.27 (m, 3H), 4.62 (t, J = 7.1 Hz, 1H), 3.39 (d, J = 7.1 Hz, 2H),
2.96−2.86 (m, 4H), 2.17−2.07 (m, 1H), 1.94−1.84 (m, 1H); 13C
NMR (75 MHz, CDCl3) δ 199.3, 140.9, 133.6, 131.9, 128.9, 127.5,
118.7, 47.8, 41.4, 29.9, 25.2; IR (neat, cm−1) 2948 (w), 2885 (w), 1700
(s), 1584 (m), 1429 (m), 1344 (m), 1275 (m), 1212 (m), 1028 (m),
978 (m), 943 (w), 766 (s), 671 (w), 624 (w), 459 (m); MS (EI, 70
eV) m/z = 318 (M+); HRMS (ESI) m/z [M + Na]+
(C12H13BrOS2Na) calcd 338.9489, found 338.9490.
2H), 7.43 (d, J = 8.9 Hz, 2H), 4.65 (t, J = 6.9 Hz, 1H), 3.33 (d, J = 6.9
Hz, 2H), 2.95 (dt, J = 11.2, 7.0 Hz, 2H), 2.89−2.77 (m, 2H), 2.18−
2.04 (m, 1H), 1.95−1.80 (m, 1H); 13C NMR (75 MHz, CDCl3) δ
194.4, 140.0, 134.9, 129.7, 129.1, 43.9, 41.6, 30.3, 25.3; IR (neat, cm−1)
2970 (w), 2900 (w), 1683 (m), 1589 (m), 1404 (m), 1347 (m), 1277
(m), 1170 (m), 1085 (m), 1050 (m), 1005 (m), 826(m), 754 (w), 562
(m), 527 (m); MS (EI, 70 eV) m/z = 272 (M+); HRMS (ESI) m/z
[M + Na]+ (C12H13ClOS2Na) calcd 294.9994, found 294.9998.
1-(4-Bromophenyl)-2-(1,3-dithian-2-yl)ethanone (3f): White
solid; Rf = 0.45 (EA/PE = 1:10); mp (°C) 119−120; isolated yield
2-(1,3-Dithian-2-yl)-1-(2-fluorophenyl)ethanone (3l): White solid;
Rf = 0.44 (EA/PE = 1:10); mp (°C) 31−32; isolated yield 75% (43
mg); 1H NMR (300 MHz, CDCl3) δ 7.86 (dd, J = 10.6, 4.6 Hz, 1H),
7.52 (ddd, J = 7.1, 6.2, 4.1 Hz, 1H), 7.19 (ddd, J = 19.6, 15.0, 9.8 Hz,
2H), 4.67 (t, J = 6.8 Hz, 1H), 3.40 (dd, J = 6.8, 2.7 Hz, 2H), 2.99−2.80
(m, 4H), 2.17−2.03 (m, 1H), 1.96−1.84 (m, 1H); 13C NMR (75
MHz, CDCl3) δ 193.6, 163.4, 160.0, 134.9, 130.7, 124.5, 116.7, 116.4,
48.6, 40.8, 29.8, 25.2; IR (neat, cm−1) 3084 (w), 2967 (w), 2890 (w),
1634 (m), 1543 (m), 1472 (m), 1390 (m), 1332 (m), 1201 (m), 1068
(m), 1023 (m), 943 (m), 770 (m), 598 (m), 469 (m); MS (EI, 70 eV)
m/z = 256 (M+); HRMS (ESI) m/z [M + Na]+ (C12H13FOS2Na)
calcd 279.0290, found 279.0294.
1
52% (37 mg); H NMR (300 MHz, CDCl3) δ 7.77 (d, J = 8.6 Hz,
2H), 7.55 (d, J = 8.6 Hz, 2H), 4.61 (t, J = 6.9 Hz, 1H), 3.27 (d, J = 6.9
Hz, 2H), 2.98−2.86 (m, 2H), 2.85−2.73 (m, 2H), 2.14−1.98 (m, 1H),
1.94−1.77 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 194.3, 135.0,
131.8, 129.5, 128.5, 43.6, 41.3, 30.0, 25.0; IR (neat, cm−1) 3080 (w),
2908 (w), 1681 (m), 1576 (m), 1417 (m),1277 (m), 1176 (m), 1068
(m), 985 (m), 818 (m), 746 (m), 664 (m), 564 (m), 452 (m); MS
(EI, 70 eV) m/z = 318 (M+); HRMS (ESI) m/z [M + Na]+
(C12H13BrOS2Na) calcd 338.9489, found 338.9492.
2-(1,3-Dithian-2-yl)-1-(4-nitrophenyl)ethanone (3g): White solid;
Rf = 0.36 (EA/PE = 1:10); mp (°C) 129−130; isolated yield 82% (52
mg); 1H NMR (300 MHz, CDCl3) δ 8.26 (d, J = 8.5 Hz, 2H), 8.18−
7.97 (m, 2H), 4.60 (t, J = 6.9 Hz, 1H), 3.34 (d, J = 6.9 Hz, 2H), 3.00−
1-(3,4-Dimethylphenyl)-2-(1,3-dithian-2-yl)ethanone (3m): White
solid; Rf = 0.47 (EA/PE = 1:10); mp (°C) 83−84; isolated yield 72%
(43 mg); 1H NMR (300 MHz, CDCl3) δ 7.73 (s, 1H), 7.69 (d, J = 7.8
1H), 7.22 (d, J = 7.6 Hz, 1H), 4.69 (t, J = 6.9 Hz, 1H), 3.32 (d, J = 6.9
D
DOI: 10.1021/acs.joc.5b00187
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The Journal of Organic Chemistry
Note
Hz, 2H), 3.02−2.91 (m, 2H), 2.89−2.80 (m, 2H), 2.31 (s, 6H), 2.18−
2.07 (m, 1H), 1.98−1.83 (m, 1H); 13C NMR (75 MHz, CDCl3) δ
195.3, 143.0, 136.9, 134.4, 129.8, 129.2, 125.9, 43.5, 41.8, 30.2, 25.2,
20.0, 19.7; IR (neat, cm−1) 3047 (w), 2982 (w), 2942 (w), 2888 (w),
1686 (s), 1606 (m), 1449 (m), 1402 (m), 1339 (m), 1247 (m), 1125
(m), 1053 (m), 988 (m), 901 (m), 826 (m), 726 (m), 606 (m), 534
(w), 432 (m); MS (EI, 70 eV) m/z = 266 (M+); HRMS (ESI) m/z
[M + Na]+ (C14H18OS2Na) calcd 289.0697, found 289.0700.
Hz, 2H), 7.34 (d, J = 6.8 Hz, 2H), 7.28−7.09 (m, 3H), 6.79 (d, J = 8.8
Hz, 2H), 4.88 (d, J = 11.1 Hz, 1H), 4.79 (d, J = 11.1 Hz, 1H), 3.70 (s,
3H), 2.88−2.64 (m, 4H), 1.97 (d, J = 13.6 Hz, 1H), 1.83−1.69 (m,
1H); 13C NMR (75 MHz, CDCl3) δ 195.2, 163.6, 135.1, 130.9, 129.5,
128.7, 128.6, 127.9, 113.7, 56.7, 55.3, 48.8, 30.0, 29.9, 25.5; IR (neat,
cm−1) 3092 (w), 3055 (w), 3040 (w), 2960 (w), 2939 (w), 2853 (w),
1660 (s), 1595(m), 1472 (m), 1440 (m), 1350 (m), 1290 (m), 1233
(m), 1200 (m), 1104 (m), 983 (m), 767 (m), 690 (m), 630 (m), 570
(m), 534 (m); MS (EI, 70 eV) m/z = 344 (M+); HRMS (ESI) m/z
[M + Na]+ (C19H20O2S2Na), calcd 367.0802, found 367.0805.
2-(1,3-Dithian-2-yl)-2-phenyl-1-(p-tolyl)ethanone (3t): White
solid; Rf = 0.37 (EA/PE = 1:10); mp (°C) 122−123; isolated yield
2-(1,3-Dithian-2-yl)-1-(thiophen-3-yl)ethanone (3n): White solid;
Rf = 0.40 (EA/PE = 1:10); mp (°C) 56−57; isolated yield 84% (46
mg); 1H NMR (300 MHz, CDCl3) δ 8.08 (d, J = 2.9 Hz, 1H), 7.56 (d,
J = 5.1 Hz, 1H), 7.39−7.25 (m, 1H), 4.67 (t, J = 6.9 Hz, 1H), 3.25 (d,
J = 6.9 Hz, 2H), 3.00−2.90 (m, 2H), 2.88−2.81 (m, 2H), 2.16−2.08
(m, 1H), 1.91−1.83 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 189.7,
141.9, 132.6, 126.9, 126.6, 45.0, 41.7, 30.4, 25.3; IR (neat, cm−1) 3077
(w), 2928 (w), 2890 (w), 1678 (s), 1507 (m), 1412 (m), 1392 (m),
1337 (w), 1232(m), 1185 (m), 1155 (m), 1078 (w), 874 (w), 808 (s),
709 (m), 619 (m); MS (EI, 70 eV) m/z = 244 (M+); HRMS (ESI) m/
z [M + Na]+ (C10H12OS3Na) calcd 266.9948, found 266.9952.
2-(1,3-Dithian-2-yl)-1-(2-methoxyphenyl)propan-1-one (3o):
Colorless oil; Rf = 0.38 (EA/PE = 1:10); isolated yield 63% (40
1
49% (36 mg); H NMR (300 MHz, CDCl3) δ 7.90 (d, J = 8.2 Hz,
2H), 7.41 (dd, J = 8.0, 1.4 Hz, 2H), 7.36−7.21 (m, 3H), 7.18 (t, J = 7.7
Hz, 2H), 5.02−4.86 (m, 2H), 2.94−2.72 (m, 4H), 2.30 (s, 3H), 2.08−
1.97 (m, 1H), 1.86−1.76 (m, 1H); 13C NMR (75 MHz, CDCl3) δ
196.0, 143.8, 134.8, 133.7, 128.9, 128.5, 128.3, 127.6, 56.5, 48.4, 29.5,
25.2, 21.2; IR (neat, cm−1) 3060 (w), 3035 (w), 2977 (w), 2932 (w),
2898 (w), 2838 (w), 1666(s), 1604 (m), 1457 (m), 1427 (m), 1327
(m), 1267 (m), 1177 (m), 1048 (m), 975 (m), 811 (m), 701 (s), 599
(m), 529 (m); MS (EI, 70 eV) m/z = 328 (M+); HRMS (ESI) m/z
[M + Na]+ (C19H20OS2Na), calcd 351.0853, found 351.0856.
1
mg); H NMR (300 MHz, CDCl3) δ 7.63 (dd, J = 7.7, 1.8 Hz, 1H),
7.52−7.40 (m, 1H), 7.06−6.92 (m, 2H), 4.44 (d, J = 8.1 Hz, 1H), 3.90
(s, 3H), 3.89−3.87 (m, 1H), 2.90−2.75 (m, 4H), 2.11−2.04 (m, 1H),
1.89−1.78 (m, 1H), 1.33 (d, J = 6.9 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ 203.7, 157.9, 133.3, 130.8, 120.8, 111.3, 55.5, 50.2, 49.3,
30.4, 29.9, 25.8, 14.5; IR (neat, cm−1) 3077 (w), 2978 (w), 2932 (w),
2912 (w), 2851 (w), 1683 (m), 1624 (s), 1523 (m), 1455 (w), 1350
(m), 1247 (s), 1145 (s), 1053 (m), 973 (m), 886 (m), 765 (m), 624
(m); MS (EI, 70 eV) m/z = 282 (M+); HRMS (ESI) m/z [M + Na]+
(C14H18O2S2Na), calcd 305.0646, found 305.0650.
2-(1,3-Dithian-2-yl)-1-(4-methoxyphenyl)propan-1-one (3p):
Colorless oil; Rf = 0.37 (EA/PE = 1:10); isolated yield 65% (41
mg); 1H NMR (300 MHz, CDCl3) δ 7.99 (d, J = 9.0 Hz, 2H), 6.97 (d,
J = 9.0 Hz, 2H), 4.44 (d, J = 9.1 Hz, 1H), 3.88 (s, 3H), 3.87−3.85 (m,
1H), 2.92−2.80 (m, 4H), 2.16−2.05 (m, 1H), 1.99−1.81 (m, 1H),
1.35 (d, J = 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 199.4, 163.7,
130.6, 129.4, 113.8, 55.4, 49.8, 44.0, 30.2, 29.8, 25.7, 15.7; IR (neat,
cm−1) 3067 (w), 2972 (w), 2927 (w), 2903 (w), 2840 (w), 1673 (m),
1604 (s), 1514 (m), 1454 (w), 1422 (m), 1237 (s), 1170 (s), 1033
(m), 975 (m), 846 (m), 796 (m), 601 (m); MS (EI, 70 eV) m/z = 282
(M+); HRMS (ESI) m/z [M + Na]+ (C14H18O2S2Na), calcd
305.0646, found 305.0651.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H NMR and 13C NMR spectra of all products. The Supporting
Information is available free of charge on the ACS Publications
website at DOI: 10.1021/acs.joc.5b00187.
AUTHOR INFORMATION
Corresponding Author
*E-mail: tangshch@lzu.edu.cn.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
for financial support of this project (Nos. 21102064 and
21102066) and a grant to X.H. (lanzhoukeji2013-4-116). We
thank Dr. Yinpeng Su (Northwest Normal University) for help
discussions.
1-(1,3-Dithian-2-yl)heptan-2-one (3q): Colorless oil; Rf = 0.52
1
(EA/PE = 1:10); isolated yield 45% (23 mg); H NMR (300 MHz,
CDCl3) δ 4.51 (t, J = 7.0 Hz, 1H), 2.96−2.82 (m, 4H), 2.79 (d, J = 7.0
Hz, 2H), 2.44 (t, J = 7.4 Hz, 2H), 2.15−2.07 (m, 1H), 1.86 (dt, J =
12.6, 2.4 Hz, 1H), 1.59 (dt, J = 14.5, 7.3 Hz, 2H), 1.33−1.24 (m, 4H),
0.89 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 206.1, 47.6,
43.5, 41.1, 41.1, 31.1, 30.1, 25.2, 23.1, 22.3, 13.8; IR (neat, cm−1) 2962
(m), 2930 (m), 2900 (m), 2865 (m), 2853 (w), 1719 (s), 1676 (w),
1472 (w), 1427 (m), 1364 (m), 1277(m), 1080 (m), 1038 (m), 911
(m), 873 (w), 776 (w), 726 (w), 661 (w), 619 (w); MS (EI, 70 eV)
m/z = 232 (M+); HRMS (ESI) m/z [M + Na]+ (C11H20OS2Na),
calcd 255.0853, found 255.0857.
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0.38 (EA/PE = 1:10); mp (°C) 136−137; isolated yield 52% (37 mg);
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J = 7.2 Hz, 1H), 7.40 (dd, J = 8.1, 7.0 Hz, 4H), 7.30 (td, J = 8.5, 4.1
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2843 (w), 1663 (s), 1581(m), 1452 (m), 1429 (m), 1329 (m), 1260
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(3s): White solid; Rf = 0.35 (EA/PE = 1:10); mp (°C) 93−94; isolated
1
yield 48% (37 mg); H NMR (300 MHz, CDCl3) δ 7.91 (d, J = 8.8
E
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DOI: 10.1021/acs.joc.5b00187
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