An operationally simple approach to (E)-α-halo vinyl sulfides and their applications for accessing stereodefined trisubstituted alkenes

Article abstract of DOI:10.1039/c3ob27307e

An operationally simple and practical protocol for the synthesis of (E)-α-halo vinyl sulfides has been achieved via a highly regio- and stereoselective hydrohalogenation of alkynyl thioethers using lithium halides in HOAc or propionic acid at room temperature. It permits the formation of (E)-α-chloro and (E)-α-bromo vinyl sulfides in satisfactory yields with good to excellent stereoselectivities. Moreover, this work results in a new method for the assembly of stereodefined (E)- or (Z)-trisubstituted alkenes featuring the first coupling of the C-X bond of (E)-α-halo vinyl sulfides followed by a subsequent Ni-catalyzed coupling of the C-S bond with Grignard reagents. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3ob27307e

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An operationally simple approach to (E)-α-halo vinyl
sulfides and their applications for accessing
stereodefined trisubstituted alkenes†
Cite this: DOI: 10.1039/c3ob27307e
Zhaozhen Yang, Xiaoyi Chen, Wei Kong, Siyuan Xia, Renwei Zheng, Fang Luo and
Gangguo Zhu*
An operationally simple and practical protocol for the synthesis of (E)-α-halo vinyl sulfides has been
achieved via a highly regio- and stereoselective hydrohalogenation of alkynyl thioethers using lithium
halides in HOAc or propionic acid at room temperature. It permits the formation of (E)-α-chloro and
(E)-α-bromo vinyl sulfides in satisfactory yields with good to excellent stereoselectivities. Moreover, this
work results in a new method for the assembly of stereodefined (E)- or (Z)-trisubstituted alkenes featur-
ing the first coupling of the C–X bond of (E)-α-halo vinyl sulfides followed by a subsequent Ni-catalyzed
coupling of the C–S bond with Grignard reagents.
Received 28th November 2012,
Accepted 26th January 2013
DOI: 10.1039/c3ob27307e
www.rsc.org/obc
Introduction
The hydrohalogenation of the C–C triple bond is one of the
most fundamental reactions in organic chemistry. However,
this reaction usually does not proceed in a preparatively useful
manner due to the formation of some regio- and stereoisomers
that are difficult to separate or purify.1 It is worth mentioning
that the hydrohalogenation of acetylenes allows straight-
forward and convenient access to alkenyl halides, which are
versatile building blocks in organic synthesis. As such, the
exploration of the regio- and stereocontrolled acetylenic hydro-
halogenation reaction is highly desirable. Along this line,
some notable results have been achieved in the hydrohalo-
genation of terminal alkynes2 or activated alkynes.3
Scheme 1 Proposed hydrohalogenation of alkynyl thioethers.
bond, thus enabling the attack of halides to the relatively posi-
tively charged carbon. Following this concept, we envisaged
that a cis-hydrohalogenation of alkynyl thioethers (Scheme 1)
would be feasible because of two important facts: (1) the nega-
tive charge of the β-carbon of 1 could result in the regioselec-
tive protonation of β-carbon;11 (2) the attack of halides from
the less hindered side (with the H atom) of vinyl cation inter-
mediate5
A
might lead to the syn-addition products
In contrast, the hydrohalogenation of internal unsymmetric
alkynes constitutes a formidable challenge.4 Indeed, some
promising examples came from the reaction of acetylenic
tosylates,5 ethers,6 alkynyl selenides,7 ynamides,8 and halo-
stereoselectively.
On the other hand, the stereodefined trisubstituted alkenes
occur in a number of natural products and related compounds
of biological and medicinal interest. Accordingly, the task of
assembly of these motifs is a significant challenge in organic
synthesis.12 Of these, Pd-catalyzed stepwise cross-coupling of
1,1-dihaloalkenes B has been particularly effective at establish-
alkynes.9 Quite recently, we10 described
a Pd-catalyzed
hydrochlorination or hydrobromination of alkynyl halides for
the regio- and stereoselective synthesis of (Z)-1,2-dihaloalk-
enes. All these aforementioned methods indicated that the
heteroatoms might play a crucial role in controlling the regio-
selectivity, presumably through polarization of the C–C triple
ing stereodefined trisubstituted alkenes
E
(Scheme 2).13
Clearly, the success of this methodology depends on the
efficient construction of compound C via the mono-coupling
of the trans C–X bond of the R1 group in B. However, this
trans-selective monosubstitution reaction does not always
proceed well and sometimes suffers from the formation of
large amounts of by-product D, which is quite difficult to sepa-
rate in some cases.
Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road,
Jinhua 321004, China. E-mail: gangguo@zjnu.cn; Fax: +86-579-82282610;
Tel: +86-579-82283702
†Electronic supplementary information (ESI) available: Spectroscopic data of
products 3, 5, and 7. CCDC 902936. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c3ob27307e
To address the challenge, we envisioned that the utiliz-
ation of stereodefined α-halo vinyl sulfides14 3 instead of
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Table 1 Hydrohalogenation of alkynyl thioethersa
Entry
R1/R2
LiX
Yieldb (%)
1
2
3
4
5
6
7
8
Ph/Et (1a)
Ph/Ph (1b)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiCl (2a)
LiBr (2b)
LiBr (2b)
LiBr (2b)
LiBr (2b)
LiBr (2b)
LiBr (2b)
LiBr (2b)
LiBr (2b)
LiI (2c)
3a 88
3b 75
3c 91
3d 83
3e 87
3f 85
3g 87
3h 79
Scheme 2 Approaches to trisubstituted alkenes.
4-F-C6H4/Et (1c)
4-Cl-C6H4/Et (1d)
4-Br-C6H4/Et (1e)
4-Me-C6H4/Et (1f)
4-t-Bu-C6H4/Et (1g)
4-OMe-C6H4/Et (1h)
3,4-(OMe)2-C6H3/Et (1i)
4-NO2-C6H4/Et (1j)
2-Naphthyl/Et (1k)
n-C9H19/Et (1l)
TBDPSO(CH2)2/Et (1m)
n-C4H9(Et)CH/Et (1n)
TBDPSOCH2(Me)CH/Et (1o)
n-C4H9/Ph (1p)
2-Thienyl (1q)
TES/Et (1r)
Ph/Et (1a)
Ph/Ph (1b)
4-Cl-C6H4/Et (1d)
4-Me-C6H4/Et (1f)
n-C4H9(Et)CH/Et (1n)
TBDPSOCH2(Me)CH/Et (1o)
n-C4H9/Ph (1p)
2-Thienyl (1q)
Ph/Et (1a)
1,1-dihaloalkenes B would enable the exclusive formation of
monosubstitution product 5 under mild conditions, due to the
obviously different reactivity of C–X and C–S bonds. Thus, a
subsequent coupling of the C–S bond can ultimately provide a
new access to stereodefined trisubstituted olefins. As such,
pursuing our interests in the functionalization of heteroatom-
substituted alkynes,10,15 we wish to report here an operation-
ally simple and mild approach to (E)-α-halo vinyl sulfides by a
highly regio- and stereoselective hydrohalogenation of alkynyl
thioethers, as well as a new entry to stereodefined trisubsti-
tuted alkenes featuring the stepwise cross-coupling reactions
of the C–X and C–S bonds of (E)-α-halo vinyl sulfides.
9
3i 75
3j 81
3k 78
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
3l 85 (92/8)c,d
3m 84 (92/8)c,d
3n 91 (94/6)c,d
3o 94 (89/11)c,d
3p 92 (90/10)c,d
3q 80
NR
3r 78e
3s 74e
3t 75e
3u 80e
3v 91 (91/9)c,d
3w 86 (94/6)c,d,f
3x 90 (91/9)c,d
3y 77
Results and discussion
At the outset, phenylethynyl thioether (1a) was treated with
3 equiv. of LiCl in HOAc3a,7b,16 at 80 °C, and the hydrochlorina-
tion product 3a was obtained in 82% yield as a 92 : 8 mixture
of E/Z isomers. We found that the reaction temperature had a
significant effect on the stereochemistry (Scheme 3). Running
the reaction at room temperature for 24 h led to (E)-α-chloro
vinyl sulfide 3a as a single E-isomer in 88% yield, while no
other regio- and stereoisomers were observed. Thus, further
substrate screenings were carried out employing 3 equiv. of
LiCl, room temperature, and HOAc as the solvent. Notably, the
stereoselectivity of 3a examined at 11%, 28% or 65% conver-
sion was uniformly >98% E, implying that the stereochemistry
is controlled by kinetic effects.
Complexg
a Reaction conditions: 1 (0.5 mmol) and LiX (1.5 mmol) in 2 mL of
HOAc at rt for 24 h. b Isolated yield. c The ratio of E/Z isomers. d The
reaction was carried out in propionic acid. e 48 h. f 15 °C. g 70 °C.
stereoselectivities. For example, 1c and 1d led to products 3c
and 3d in excellent yields (Table 1, entries 3 and 4). In con-
trast, under the standard conditions for 4 h, the aliphatic sub-
strate 1l delivered 86% yield of 3l as a 4 : 1 mixture of E/Z
isomers. Fortunately, we found that the use of less polar and
acidic solvents could obviously slow down the hydrohalogena-
tion reaction, thereby improving the stereoselectivity. As a
result, the reaction performed in propionic acid at room temp-
erature for 24 h provided 3l in 85% yield with a high stereo-
selectivity (E/Z = 92/8) (Table 1, entry 12). Other acidic solvents
proved to be less effective. Therefore, we decided to use prop-
ionic acid as the solvent for the reaction of aliphatic alkynyl
thioethers. Pleasingly, the steric demanding substrates 1n and
1o offered excellent yields of hydrochlorination products 3n
and 3o in good stereoselectivities under the modified con-
ditions (Table 1, entries 14 and 15).
As shown in Table 1, the hydrohalogenation process exhib-
ited good compatibility with a wide range of substituted
aromatic rings in substrate 1. Both electron-poor and electron-
rich aromatic acetylenic thioethers successfully afforded
(E)-α-chloro vinyl sulfides in good yields and excellent
Next, the hydrobromination of acetylenic thioethers was
also briefly investigated, and as expected, the reaction occurred
smoothly to generate the desired products in satisfactory
yields by the utilization of LiBr. For example, the reaction of 1a
and 1b proceeded successfully to afford (E)-α-bromo vinyl sul-
fides 3r and 3s in good yields, albeit in a prolonged reaction
time (48 h) (Table 1, entries 19 and 20). Likewise, aliphatic
acetylenic thioethers such as 1n, 1o, and 1p resulted in the
Scheme 3 Temperature effect.
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desired products in excellent yields and good stereoselecti-
Further optimization demonstrated that the base plays a
vities (Table 1, entries 23–25). We also tried to extend this reac- key role in this reaction. For example, the utilization of Cs2CO3
tion to the access of (E)-α-iodo vinyl sulfides; however, only low and t-BuOK provided high yields of 5a in a single Z-isomer,
conversion was observed for the hydroiodination of 1a at room while the reaction performed with K3PO4, KOH, CsF, or
temperature, while the reaction run at a higher temperature K2CO3 resulted in significantly decreased stereoselectivities
(70 °C) just gave a complex mixture (Table 1, entry 27). The (Table 2, entries 2–8). Experiments with other solvents such as
regio- and stereochemistry of this transformation was deter- toluene, dioxane, and DMF had no benefical consequences
mined by the 1H NMR and 13C NMR analysis of the products,6b (Table 2, entries 9–11). Interestingly, PPh3 proved to be the
and further confirmed by the X-ray diffraction analysis of 3s.
most effective ligand for this reaction, whereas other
As such, we have developed a highly regio- and stereo- ligands such as P(o-tol)3, P(2-furyl)3, PCy3, and dppe were
selective hydrohalogenation of acetylenic thioethers featuring found to be inferior ones (Table 2, entries 14–18). Finally, the
the use of readily available lithium halides in weakly acidic sol- optimized reaction conditions for the Suzuki coupling of 3
vents such as HOAc or propionic acid, in which (E)-α-halo vinyl consisted of 5 mol% of Pd(OAc)2, 10 mol% of PPh3, 1.3 equiv.
sulfides were synthesized in high yields with good to excellent of R3B(OH)2, and 1.5 equiv. of Cs2CO3 in THF at 40 °C for 5 h,
stereoselectivities. In comparison to the previous reports using which produced the stereoisomerically pure 5a in 91% isolated
the TMSX/MeOH reaction system,6b our protocol developed here yield.
avoids the use of moisture sensitive reagents, anhydrous metha-
Having identified the optimal reaction conditions, we then
nol, and strict reaction conditions (−40 °C for TMSBr/MeOH). investigated the scope of the Suzuki coupling of 3. As shown in
Therefore, it provides an operationally simple, highly efficient, Table 3, the reaction was widely applicable for the coupling of
and practical alternative to assemble (E)-α-halo vinyl sulfides.
various substituted α-halo vinyl sulfides, allowing facile access
Then, we turned our attention to the synthesis of stereo- to polysubstituted vinylic sulfides in good yields. For instance,
defined trisubstituted olefins from the (E)-α-halo vinyl sulfides 3c and 3h produced the desired products 5c and 5h in 87%
thus obtained. Firstly, 3a was treated with 1.3 equiv. of PhB- and 89% yield, respectively (Table 3, entries 3 and 9). In con-
(OH)2 (4a), 5 mol% of Pd(OAc)2, 20 mol% of PPh3, and 1.5 trast, the substrate 3j, with a strong electron-withdrawing sub-
equiv. of KF in THF at 40 °C for 12 h. As expected, the Suzuki17 stituent (NO2), only led to traces of the desired product due to
coupling of 3a occurred exclusively at the C–X bond to furnish the dehydrochlorination process under the standard con-
vinyl sulfide 5a in 84% yield, albeit at a 3 : 1 Z/E mixture ditions (Table 3, entry 11). Pleasingly, the use of steric
(Table 2, entry 1), and the double substitution product could demanding substrate 3n also resulted in 5l in high yield
not be observed by GC, GC-MS or NMR.
(Table 3, entry 14). Meanwhile, α-bromo vinyl sulfides coupled
successfully with 4a to furnish the corresponding products in
good yields (Table 3, entries 15–17).
Table 2 Optimization of the Suzuki coupling of 3aa
Then, the scope of this reaction with respect to boronic
acids was briefly examined. As an example, the alkenyl boronic
acid 4b was an effective substrate for this reaction (Table 3,
entry 18). It should be noted that the steric hindrance has
some effect on this Suzuki coupling reaction, and for instance,
the reaction of 4-tolylboronic acid (4c), 3-tolylboronic acid (4d),
and 2-tolylboronic acid (4e) formed the products 5n, 5o, and
5p in respective yields of 93%, 86%, and 62% (Table 3, entries
19–21). Heteroaromatic boronic acids such as 2-thienylboronic
acid (4j) and 2-furylboronic acid (4k) coupled smoothly with 3a
to afford the desired products in good yields (Table 3, entries
26 and 27). In addition, methylboronic acid (4l) turned out to
be a competent coupling partner and provided 5w in a reason-
able yield (Table 3, entry 28), while BuB(OH)2 (4m) was found
to be almost unreactive even at an elevated temperature
(70 °C). The stereochemistry of resultant vinyl sulfides 5 was
determined by comparison with the literature data18 as well as
NOE measurements.
Ligand/
Entry equiv.
Time Yieldb
Base
Solvent
(h)
(%)
Z/Ec
1
2
3
4
5
6
7
8
PPh3/0.2
KF
THF
THF
THF
THF
THF
THF
12
12
12
12
12
12
5
5
5
5
5
24
5
5
5
5
5
5
84
87
82
67
76
90
82
88
65
77
83
65
46
91
78
85
62
87
75/25
61/39
91/9
56/44
95/5
PPh3/0.2
PPh3/0.2
PPh3/0.2
PPh3/0.2
PPh3/0.2
PPh3/0.2
PPh3/0.2
PPh3/0.2
PPh3/0.2
PPh3/0.2
PPh3/0.2
/
PPh3/0.1
P(o-tol)3/0.1
P(2-furyl)3/0.1 Cs2CO3 THF
PCy3/0.1
dppe/0.05
K3PO4
KOH
K2CO3
NaOEt
CsF
t-BuOK THF
Cs2CO3 THF
Cs2CO3 Toluene
Cs2CO3 Dioxane
Cs2CO3 DMF
Cs2CO3 THF
Cs2CO3 THF
Cs2CO3 THF
Cs2CO3 THF
91/9
>98/2
>98/2
62/38
93/7
9
10
11
12d
13
14
15
16
17
18
96/4
>98/2
90/10
>98/2
88/12
95/5
90/10
68/32
Moreover, the (E)-α-halo vinyl sulfides 3 exhibited versatile
reactivity in other transition-metal-catalyzed cross-coupling
reactions. For example, the Negishi coupling19 of 3a with
either PhZnBr or MeZnBr successfully furnished the desired
products 5a or 5w in good yields (unoptimized). Thus, it pro-
vided an effective alternative to assemble the vinyl sulfides 5.
Additionally, the Sonogashira coupling20 of 3a with
Cs2CO3 THF
Cs2CO3 THF
a Reaction conditions: 3a (0.5 mmol), 4a (0.65 mmol), Pd(OAc)2
(0.025 mmol), ligand (0–0.1 mmol), base (0.75 mmol), THF, 40 °C.
b Isolated yield. c Determined by GC. d Room temperature.
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Table 3 Synthesis of vinyl sulfide 5 via the Suzuki coupling of 3a
Table 4 Synthesis of trisubstituted alkenes from 5a
Yieldb
(%)
Entry R1/R2/X (3)
R3 (4)
Yieldb (%)
Entry R1/R2/R3
R4MgX (6)
1
2
3
4
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
Ph/Et/Cl (3a)
Ph/Ph/Cl (3b)
Ph (4a)
Ph (4a)
Ph (4a)
Ph (4a)
Ph (4a)
Ph (4a)
Ph (4a)
Ph (4a)
91 (5a)
84 (5b)
87 (5c)
86 (5d)
79 (5e)
85 (5f)
90 (5g)
89 (5h)
94 (5i)
Trace
82 (5j)
85 (5k)c
89 (5l)c
87 (5a)
83 (5d)
87 (5f)
71 (5m)
93 (5n)
86 (5o)
62 (5p)
89 (5q)
1
2
3
4
5
6
7
8
Ph/Et/Ph (5a)
Ph/Ph/Ph (5b)
4-F-C6H4/Et/Ph (5c)
4-Me-C6H4/Et/Ph (5f)
4-t-Bu-C6H4/Et/Ph (5g)
4-OMe-C6H4/Et/Ph (5h)
3,4-(OMe)2-C6H3/Et/Ph (5i) MeMgCl (6a)
2-Naphthyl/Et/Ph (5j)
n-C9H19/Et/Ph (5k)
Ph/Et/4-Me-C6H4 (5n)
Ph/Et/3-Me-C6H4 (5o)
Ph/Et/2-Me-C6H4 (5p)
Ph/Et/4-OMe-C6H4 (5q)
Ph/Et/3,4-(OMe)2-C6H3 (5r) MeMgCl (6a)
Ph/Et/2-Naphthyl (5t)
Ph/Et/Ph (5a)
n-C9H19/Et/Ph (5k)
Ph/Et/Me (5w)
Ph/Et/4-F-C6H4 (5s)
Ph/Et/4-F-C6H4 (5s)
MeMgCl (6a)
MeMgCl (6a)
MeMgCl (6a)
MeMgCl (6a)
MeMgCl (6a)
MeMgCl (6a)
86 (7a)
76 (7a)
75 (7b)
80 (7c)
81 (7d)
80 (7e)
84 (7f)
78 (7g)
71 (7h)
89 (7i)
75 (7j)
Trace
4-F-C6H4/Et/Cl (3c)
4-Cl-C6H4/Et/Cl (3d)
4-Br-C6H4/Et/Cl (3e)
4-Me-C6H4/Et/Cl (3f)
4-t-Bu-C6H4/Et/Cl (3g)
4-OMe-C6H4/Et/Cl (3h)
MeMgCl (6a)
MeMgCl (6a)
MeMgCl (6a)
MeMgCl (6a)
MeMgCl (6a)
MeMgCl (6a)
3,4-(OMe)2-C6H3/Et/Cl (3i) Ph (4a)
9
4-NO2-C6H4/Et/Cl (3j)
2-Naphthyl/Et/Cl (3k)
n-C9H19/Et/Cl (3l)
n-C4H9(Et)CH/Et/Cl (3n)
Ph/Et/Br (3r)
4-Cl-C6H4/Et/Br (3t)
4-Me-C6H4/Et/Br (3u)
Ph/Et/Cl (3a)
Ph/Et/Cl (3a)
Ph/Et/Cl (3a)
Ph/Et/Cl (3a)
Ph/Et/Cl (3a)
Ph/Et/Cl (3a)
Ph/Et/Cl (3a)
Ph/Et/Cl (3a)
Ph/Et/Cl (3a)
Ph/Et/Cl (3a)
Ph/Et/Cl (3a)
Ph (4a)
Ph (4a)
Ph (4a)
Ph (4a)
Ph (4a)
Ph (4a)
Ph (4a)
(E)-Styryl (4b)
4-Me-C6H4 (4c)
3-Me-C6H4 (4d)
2-Me-C6H4 (4e)
4-OMe-C6H4 (4f)
10
11
12c
13
14
15
16
17c
18c
19c
20c
82 (7k)
80 (7l)
87 (7m)
Trace
MeMgCl (6a)
EtMgBr (6b)
4-MeO-C6H4MgBr (6c) 61 (7n)
PhMgCl (6d) 71 (7o)
4-MeO-C6H4MgBr (6c) 65 (7p)
4-Me-C6H4MgBr (6e) 70 (7q)
3,4-(OMe)2-C6H3 (4g) 86 (5r)
a Reaction conditions: 5 (0.25 mmol), 6 (0.75 mmol), Ni(PPh3)2Cl2
4-F-C6H4 (4h)
2-Naphthyl (4i)
2-Thienyl (4j)
2-Furyl (4k)
Me (4l)
80 (5s)
81 (5t)
76 (5u)
75 (5v)
66 (5w)
(0.025 mmol), THF, rt. b Isolated yield. c 50 °C.
and 7j in respective yields of 89% and 75%, while the coupling
of 5p (R3 = 2-Me-C6H4) almost did not take place even at a
higher temperature of 50 °C, indicating that the coupling of
the C–S bond was sensitive to steric hindrance (Table 4,
entries 10–12).
a Reaction conditions:
3 (0.5 mmol), 4 (0.65 mmol), Pd(OAc)2
(0.025 mmol), PPh3 (0.05 mmol), Cs2CO3 (0.75 mmol), THF, 40 °C, 5 h.
b Isolated yield. c Z/E > 95/5.
As for other Grignard reagents, EtMgBr (6b), for instance,
only afforded traces of the desired product because of the
occurrence of the β-H elimination reaction (Table 4, entry 16).
In contrast, 4-MeO-C6H4MgBr (6c) coupled smoothly with 5k
to give (Z)-trisubstituted alkene 7n in a reasonable yield, while
the coupling of PhMgCl (6d) with 5w afforded 71% of (Z)-tri-
substituted alkene 7o23 (Table 4, entries 17 and 18). Moreover,
both 4-MeO-C6H4MgBr (6c) and 4-Me-C6H4MgBr (6e) reacted
smoothly with 5s to provide the desired products in good
yields (Table 4, entries 19 and 20).
Scheme 4 Other cross-coupling reactions of 3a.
Therefore, we have realized a novel approach to stereo-
defined (E)- or (Z)-trisubstituted alkenes by the iterative cross-
phenylacetylene and trimethylsilylacetylene proceeded well to coupling of the C–X and C–S bonds of (E)-α-halo vinyl sulfides
give 5x and 5y in high yields (Scheme 4). (3). It is worth mentioning that the selective coupling of the
Next, the elaboration of trisubstituted alkenes was investi- C–X bond of 3 is much more easy to be implemented than that
gated by the Ni-catalyzed coupling of the C–S bond with of 1,1-dihaloalkenes B, due to the better reactivity of the C–X
Grignard reagents21 and the results are summarized in bond than the C–S bond towards the transition-metal-cata-
Table 4. For example, treating 5a with 10 mol% of Ni(PPh3)2Cl2 lyzed cross-coupling reactions, thus enabling one to avoid the
and 3 equiv. of MeMgCl (6a) in THF at room temperature utilization of elaborate ligands and substrate-dependent reac-
resulted in the establishment of trisubstituted alkene 7a22 in tion conditions. Although the one-pot tandem cross-coupling
86% yield (Table 4, entry 1). Regarding the variation of the aro- of the C–X and C–S bonds of 3 has not been achieved at the
matic group of 5, common functional groups were well toler- current stage, the two-step strategy developed here will still
ated (Table 4, entries 3–8). The reaction of 5n (R3 = 4-Me-C6H4) represent a promising approach to stereodefined (E)- or (Z)-tri-
and 5o (R3 = 3-Me-C6H4) proceeded successfully to deliver 7i substituted alkenes.
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189 (3), 187 (8), 152 (100); HRMS (EI) calcd for C10H10ClFS
(M+) 216.0176, found 216.0177.
Conclusions
In conclusion, we have developed an operationally simple and
Compound 3d. 83% yield (96 mg), colorless oil; 1H NMR
practical protocol for the access of (E)-α-halo vinyl sulfides by a (CDCl3, 400 MHz) δ 1.30 (t, J = 7.2 Hz, 3H), 2.97 (q, J = 7.6 Hz,
highly regio- and stereoselective hydrohalogenation of alkynyl 2H), 6.96 (s, 1H), 7.32 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.4 Hz,
thioethers featuring the use of lithium halides in HOAc or 2H); 13C NMR (CDCl3, 100 MHz) δ 14.6, 28.1, 128.3, 130.3,
propionic acid at room temperature. Both (E)-α-bromo and 130.3, 132.9, 133.2, 133.4; MS (EI, m/z) 236 (4), 234 (32), 232
(E)-α-chloro vinyl sulfides could be synthesized in satisfactory (M+, 52), 199 (3), 197 (9); HRMS (EI) calcd for C10H10Cl2S (M+)
yields with good to excellent stereoselectivities under mild con- 231.9880, found 231.9877.
ditions. In addition, a new method for the elaboration of
Compound 3e. 87% yield (120 mg), colorless oil; 1H NMR
stereodefined (E)- or (Z)-trisubstituted alkenes has been (CDCl3, 400 MHz) δ 1.29 (t, J = 7.4 Hz, 3H), 2.95 (q, J = 7.4 Hz,
achieved through the stepwise cross-coupling reactions of the 2H), 6.92 (s, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 8.4 Hz,
C–X and C–S bonds of (E)-α-halo vinyl sulfides.
2H); 13C NMR (CDCl3, 100 MHz) δ 14.7, 28.3, 121.7, 130.7,
131.4, 131.4, 133.1, 133.8; HRMS (ESI) calcd for C10H10BrClS
(M+) 275.9375, found 275.9370.
Compound 3f. 85% yield (90 mg), colorless oil; 1H NMR
(CDCl3, 400 MHz) δ 1.31 (t, J = 7.4 Hz, 3H), 2.37 (s, 3H), 2.97
(q, J = 7.4 Hz, 2H), 7.02 (s, 1H), 7.18 (d, J = 8.0 Hz, 2H), 7.46 (d,
J = 8.0 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 14.7, 21.3, 28.2,
128.5, 128.9, 129.1, 132.2, 134.7, 137.9; MS (EI, m/z) 214 (35),
212 (M+, 100), 185 (11), 183 (31), 148 (88); HRMS (EI) calcd for
C11H13ClS (M+) 212.0426, found 212.0428.
Experimental section
General
Pd(PPh3)4, Pd(OAc)2, Pd(dba)2, and other reagents were
obtained commercially and used without further purification.
Column chromatography was performed using silica gel
(300–400 mesh). The 1H NMR and 13C NMR spectra were
recorded on 400 or 600 MHz NMR spectrometers. High-resolu-
tion mass spectra (HRMS) analyses were carried out using
electron ionization–quadrupole or electrospray ionization–
time-of-flight (ESI-TOF) mass spectrometry. Melting points
were obtained on a melting point apparatus with open capil-
lary tubes and are uncorrected.
Compound 3g. 87% yield (110 mg), colorless oil; 1H NMR
(CDCl3, 400 MHz) δ 1.32–1.37 (m, 12H), 3.00 (q, J = 7.4 Hz,
2H), 7.04 (s, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.4 Hz,
2H); 13C NMR (CDCl3, 100 MHz) δ 14.6, 28.1, 31.2, 34.6, 125.1,
128.4, 128.9, 132.0, 134.4, 150.9; MS (EI, m/z) 256 (15), 254
(M+, 48), 239 (11), 227 (7), 225 (20); HRMS (EI) calcd for
C14H19ClS (M+) 254.0896, found 254.0910.
General procedure for hydrohalogenation of alkynyl thioethers
Compound 3h. 79% yield (90 mg), colorless oil; 1H NMR
To a solution of 1a (81 mg, 0.5 mmol) in 2 mL of acetic acid (CDCl3, 400 MHz) δ 1.31 (t, J = 7.4 Hz, 3H), 2.95 (t, J = 7.4 Hz,
was added LiCl (64 mg, 1.5 mmol). After stirring at room temp- 2H), 3.83 (s, 3H), 6.89 (d, J = 8.8 Hz, 2H), 6.98 (s, 1H), 7.53 (d,
erature for 24 h, the reaction mixture was quenched with J = 8.8 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 14.6, 28.2, 55.3,
water, extracted with ethyl acetate, washed with brine, dried 113.6, 127.1, 127.6, 130.6, 134.5, 159.2; MS (EI, m/z) 230 (27),
over Na2SO4, and concentrated. Column chromatography on 228 (M+, 100), 195 (13), 193 (38), 179 (73); HRMS (EI) calcd for
silica gel (petroleum ether/EtOAc = 100/1) gave 87 mg (88%) of C11H13ClOS (M+) 228.0376, found 228.0376.
1
3a as a colorless oil. H NMR (CDCl3, 400 MHz) δ 1.32 (t, J =
Compound 3i. 75% yield (97 mg), colorless oil; 1H NMR
7.4 Hz, 3H), 2.97 (q, J = 7.4 Hz, 2H), 7.04 (s, 1H), 7.29–7.31 (m, (CDCl3, 400 MHz) δ 1.31 (t, J = 7.4 Hz, 3H), 2.96 (q, J = 7.4 Hz,
1H), 7.37 (t, J = 7.2 Hz, 2H), 7.55 (d, J = 7.6 Hz, 2H); 13C NMR 2H), 3.90 (s, 3H), 3.90 (s, 3H), 6.84 (d, J = 8.4 Hz, 1H), 6.96 (s,
(CDCl3, 100 MHz) δ 14.7, 28.2, 127.8, 128.2, 129.2, 129.2, 1H), 7.05–7.08 (m, 1H), 7.30 (d, J = 2.0 Hz, 1H); 13C NMR
134.5, 134.9; MS (EI, m/z) 200 (22), 198 (M+, 65), 171 (10), 169 (CDCl3, 100 MHz) δ 14.7, 28.2, 55.9, 55.9, 110.7, 112.0, 122.6,
(26), 134 (100); HRMS (EI) calcd for C10H11ClS (M+) 198.0270, 127.2, 127.8, 134.6, 148.4, 148.8; MS (EI, m/z) 260 (23), 258
found 198.0275.
Compound 3b. 75% yield (92 mg), colorless oil; 1H NMR C12H15ClO2S (M+) 258.0481, found 258.0480.
(M+, 75), 231 (30), 229 (87), 194 (100); HRMS (EI) calcd for
(CDCl3, 400 MHz) δ 7.25 (s, 1H), 7.30–7.41 (m, 6H), 7.45 (d, J =
Compound 3j. 81% yield (98 mg), yellow oil; 1H NMR
8.0 Hz, 2H), 7.62 (d, J = 7.6 Hz, 2H); 13C NMR (CDCl3, (CDCl3, 400 MHz) δ 1.32 (t, J = 7.4 Hz, 3H), 3.02 (q, J = 7.4 Hz,
100 MHz) δ 127.6, 127.7, 128.4, 128.5, 129.1, 129.2, 130.5, 2H), 7.00 (s, 1H), 7.67–7.70 (m, 2H), 8.18–8.20 (m, 2H);
132.7, 134.6, 137.6; MS (EI, m/z) 248 (9), 246 (M+, 32), 219 (13), 13C NMR (CDCl3, 100 MHz) δ 14.8, 28.5, 123.5, 129.7, 131.2,
217 (40), 182 (75); HRMS (EI) calcd for C14H11ClS (M+) 134.5, 141.3, 146.5; MS (EI, m/z) 245 (2), 243 (M+, 6), 168 (13),
246.0270, found 246.0268.
Compound 3c. 91% yield (98 mg), colorless oil; 1H NMR 243.0121, found 243.0119.
166 (41), 130 (100); HRMS (EI) calcd for C10H10ClNO2S (M+)
(CDCl3, 400 MHz) δ 1.30 (t, J = 7.4 Hz, 3H), 2.96 (q, J = 7.4 Hz,
Compound 3k. 78% yield (97 mg), colorless oil; 1H NMR
2H), 6.98 (s, 1H), 7.02–7.07 (m, 2H), 7.51–7.55 (m, 2H); (CDCl3, 400 MHz) δ 1.36 (t, J = 7.4 Hz, 3H), 3.02 (q, J = 7.4 Hz,
13C NMR (CDCl3, 100 MHz) δ 14.7, 28.2, 115.2 (d, J = 21.5 Hz), 2H), 7.22 (s, 1H), 7.50–7.53 (m, 2H), 7.75–7.77 (m, 1H),
129.3 (d, J = 2.4 Hz), 131.0 (d, J = 8.0 Hz), 131.1 (d, J = 3.4 Hz), 7.83–7.88 (m, 3H), 7.99 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ
133.4, 162.1 (d, J = 247.2 Hz); MS (EI, m/z) 218 (4), 216 (M+, 12), 14.7, 28.3, 126.3, 126.4, 126.7, 127.6, 127.7, 128.3, 128.8, 129.8,
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132.4, 132.7, 133.1, 134.5; MS (EI, m/z) 250 (3), 248 (M+, 12), 7.55 (s, 1H), 7.64 (d, J = 7.2 Hz, 2H); 13C NMR (CDCl3,
221 (8), 219 (25), 184 (37); HRMS (EI) calcd for C14H13ClS (M+) 100 MHz) δ 116.3, 127.7, 128.5, 128.6, 129.0, 129.3, 130.2,
248.0426, found 248.0422.
133.8, 135.5, 142.3; MS (EI, m/z) 292 (8), 290 (M+, 10), 221 (7),
Compound 3l. 85% yield (105 mg), colorless oil, E/Z = 92/8; 210 (41), 178 (100), 121 (52); HRMS (EI) calcd for C14H11BrS
1H NMR (CDCl3, 600 MHz) δ 0.88 (t, J = 6.8 Hz, 3H), 1.23–1.43 (M+) 289.9765, found 289.9760. Crystal data for 3s (C14H11BrS,
(m, 17H), 2.25 (dd, J = 14.6, 7.4 Hz, 2H), 2.82 (q, J = 7.3 Hz, 291.20) orthorhombic, space group P2(1)2(1)2(1), a = 6.0206(4)
2H), 6.08 (t, J = 7.6 Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ 14.1, Å, b = 10.2488(7) Å, c = 20.3688(13) Å, volume = 1256.83(14) Å3,
14.6, 22.7, 27.1, 29.0, 29.1, 29.3, 29.4, 29.6, 30.6, 31.9, 126.7, Z = 4, specimen 0.403 × 0.204 × 0.057 mm3, T = 296(2) K,
138.4; MS (EI, m/z) 250 (5), 248 (M+, 12), 221 (6), 219 (18); SIEMENS
P4
diffractometer,
absorption
coefficient
HRMS (EI) calcd for C13H25ClS (M+) 248.1365, found 248.1357. 3.405 mm−1, reflections collected 8909, independent reflec-
Compound 3m. 84% yield (170 mg), colorless oil, E/Z = 92/8; tions 2206 [R(int) = 0.0350], refinement by full-matrix least-
1H NMR (CDCl3, 600 MHz) δ 1.10 (s, 9H), 1.25 (t, J = 7.3 Hz, squares on F2, data/restraints/parameters 2206/0/145, good-
3H), 2.57 (dd, J = 13.9, 6.5 Hz, 2H), 2.83 (q, J = 7.3 Hz, 2H), ness-of-fit on F2 = 1.059, final R indices [I > 2σ(I)] R1 = 0.0353,
3.74 (dt, J = 12.9, 6.5 Hz, 2H), 6.18 (t, J = 7.5 Hz, 1H), 7.36–7.55 wR2 = 0.0740, R indices (all data) R1 = 0.0682, wR2 = 0.0815,
(m, 6H), 7.60–7.82 (m, 4H); 13C NMR (CDCl3, 150 MHz) δ 14.6, largest diff peak and hole 0.573 and −0.371 e Å−3. CCDC
19.2, 26.8, 27.2, 34.0, 62.7, 127.7, 128.6, 129.7, 133.7, 134.7, 902936 (3s) contains the supplementary crystallographic data
135.6; HRMS (ESI) calcd for C22H29ClOSSi (M+) 404.1397, for this paper.
found 404.1396.
Compound 3t. 75% yield (104 mg), colorless oil; 1H NMR
Compound 3n. 91% yield (100 mg), colorless oil, E/Z = 94/6; (CDCl3, 400 MHz) δ 1.30 (t, J = 7.4 Hz, 3H), 2.94 (q, J = 7.4 Hz,
1H NMR (CDCl3, 400 MHz) δ 0.87 (q, J = 7.3 Hz, 6H), 1.15–1.55 2H), 7.25 (s, 1H), 7.32 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.4 Hz,
(m, 11H), 2.46–2.61 (m, 1H), 2.82 (q, J = 7.3 Hz, 2H), 5.79 (d, 2H); 13C NMR (CDCl3, 100 MHz) δ 14.6, 30.5, 120.3, 128.4,
J = 10.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 11.8, 14.0, 14.7, 130.4, 133.6, 134.2, 138.0; MS (EI, m/z) 280 (11), 278 (40), 276
22.8, 27.2, 28.2, 29.5, 34.7, 42.6, 126.6, 142.8; MS (EI, m/z) (M+, 54), 214 (60), 212 (63); HRMS (EI) calcd for C10H10BrClS,
222 (3), 220 (M+, 8), 171 (10), 169 (26), 134 (100); HRMS (EI) (M+) 275.9375, found 275.9379.
calcd for C11H21ClS (M+) 220.1052, found 220.1055.
Compound 3u. 80% yield (106 mg), colorless oil; 1H NMR
Compound 3o. 94% yield (196 mg), colorless oil, E/Z = 89/11; (CDCl3, 400 MHz) δ 1.31 (t, J = 7.4 Hz, 3H), 2.36 (s, 3H), 2.94
1H NMR (CDCl3, 400 MHz) δ 0.99–1.10 (m, 12H), 1.23–1.28 (q, J = 7.4 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 7.30 (s, 1H), 7.48 (d,
(m, 3H), 2.77–2.88 (m, 2H), 2.92–3.08 (m, 1H), 3.57 (dd, J = J = 8.0 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 14.5, 21.4, 30.4,
15.1, 5.9 Hz, 2H), 5.98 (d, J = 9.7 Hz, 1H), 7.35–7.52 (m, 6H), 118.5, 129.0, 129.1, 133.0, 138.0, 139.6; MS (EI, m/z) 258 (36),
7.69 (d, J = 7.0 Hz, 4H); 13C NMR (CDCl3, 100 MHz) δ 14.6, 256 (M+, 34), 229 (7), 227 (8), 188 (70); HRMS (EI) calcd for
16.7, 19.3, 26.9, 27.2, 38.4, 67.8, 127.7, 129.6, 133.7, 135.6, C11H13BrS (M+) 255.9921, found 255.9920.
135.7, 140.9; HRMS (ESI) calcd for C23H31ClOSSi (M+)
418.1553, found 418.1560.
Compound 3v. 91% yield (120 mg), colorless oil, E/Z = 91/9;
1H NMR (CDCl3, 400 MHz) δ 0.85–0.90 (m, 6H), 1.05–1.54 (m,
Compound 3p.6b 92% yield (104 mg), colorless oil, E/Z = 11H), 2.52–2.59 (m, 1H), 2.80 (q, J = 7.3 Hz, 2H), 6.06 (d, J =
90/10; 1H NMR (CDCl3, 600 MHz) δ 0.93–1.01 (m, 3H), 1.36–1.52 10.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 11.9, 14.1, 14.6,
(m, 4H), 2.42 (dd, J = 14.8, 7.5 Hz, 2H), 6.30–6.38 (m, 1H), 22.8, 28.0, 28.9, 29.5, 34.6, 43.8, 116.0, 147.9; MS (EI, m/z)
7.28–7.32 (m, 1H), 7.34–7.47 (m, 4H); 13C NMR (CDCl3, 266 (9), 264 (M+, 10), 237 (11), 235 (12), 208 (10), 206 (10);
150 MHz) δ 13.9, 22.3, 30.8, 31.1, 125.3, 127.1, 129.1, 129.6, HRMS (EI) calcd for C11H21BrS (M+) 264.0547, found 264.0546.
133.3, 141.4; MS (EI, m/z) 228 (7), 226 (M+, 20), 191 (12),
183 (23), 181 (72). 1H NMR and 13C NMR spectra data are in 1H NMR (CDCl3, 400 MHz) δ 1.0 (d, J = 6.8 Hz, 3H), 1.14 (s,
good agreement with those obtained by Jin’s method.6b
9H), 1.28 (t, J = 7.4 Hz, 3H), 2.83 (q, J = 7.4 Hz, 2H), 3.01–3.20
Compound 3w. 86% yield (199 mg), colorless oil, E/Z = 94/6;
Compound 3q. 80% yield (82 mg), colorless oil; 1H NMR (m, 1H), 3.58–3.61 (m, 2H), 6.31 (d, J = 9.6 Hz, 1H), 7.43–7.49
(CDCl3, 400 MHz) δ 1.35 (t, J = 7.6 Hz, 3H), 2.99 (q, J = 7.4 Hz, (m, 6H), 7.73–7.76 (m, 4H); 13C NMR (CDCl3, 100 MHz) δ 14.6,
2H), 6.98–7.03 (m, 1H), 7.13–7.16 (m, 1H), 7.23 (s, 1H), 16.6, 19.4, 26.9, 28.9, 39.5, 67.6, 117.0, 127.8, 129.7, 133.7,
7.31–7.35 (m, 1H); 13C NMR (CDCl3, 100 MHz) δ 14.6, 28.5, 135.7, 146.0; HRMS (ESI) calcd for C23H31BrOSSi (M+)
126.1, 126.3, 127.0, 129.8, 129.9, 138.1; HRMS (EI) calcd for 462.1048, found 462.1051.
C8H9ClS2 (M+) 203.9834, found 203.9839.
Compound 3x.6b 90% yield (122 mg), colorless oil, E/Z = 91/
Compound 3r. 78% yield (94 mg), colorless oil; 1H NMR 9; 1H NMR (CDCl3, 600 MHz) δ 0.96–1.10 (m, 3H), 1.40–1.50
(CDCl3, 400 MHz) δ 1.30 (t, J = 7.4 Hz, 3H), 2.94 (q, J = 7.4 Hz, (m, 4H), 2.39–2.42 (m, 2H), 6.62–6.64 (m, 1H), 7.31–7.33 (m,
2H), 7.30–7.38 (m, 4H), 7.57 (d, J = 7.6 Hz, 2H); 13C NMR 1H), 7.37–7.41 (m, 4H); 13C NMR (CDCl3, 150 MHz) δ 13.9,
(CDCl3, 100 MHz) δ 14.5, 30.4, 119.6, 128.0, 128.2, 129.2, 22.3, 30.9, 31.9, 113.3, 127.1, 129.1, 129.4, 134.1, 146.4.
135.8, 139.4; MS (EI, m/z) 244 (12), 242 (M+, 11), 215 (43), 1H NMR and 13C NMR spectra data are in good agreement
213 (45); HRMS (EI) calcd for C10H11BrS (M+) 241.9765, with those obtained by Jin’s method.6b
found 241.9767.
Compound 3y. 77% yield (95 mg), colorless oil; 1H NMR
Compound 3s. 74% yield (107 mg), white solid, mp (CDCl3, 600 MHz) δ 1.31 (t, J = 7.4 Hz, 3H), 2.94 (q, J = 7.4 Hz,
117–118 °C; 1H NMR (CDCl3, 400 MHz) δ 7.33–7.46 (m, 8H), 2H), 6.97 (dd, J = 5.0, 3.7 Hz, 1H), 7.13 (d, J = 3.4 Hz, 1H), 7.32
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(d, J = 5.0 Hz, 1H), 7.45 (s, 1H); 13C NMR (CDCl3, 150 MHz) 2.49 (q, J = 7.4 Hz, 2H), 6.86 (s, 1H), 7.23–7.25 (m, 2H),
δ 14.5, 30.3, 115.5, 126.2, 127.3, 130.3, 134.3, 139.0; HRMS (EI) 7.36–7.38 (m, 1H), 7.41–7.45 (m, 2H), 7.64–7.69 (m, 4H);
calcd for C8H9BrS2 (M+) 247.9329, found 247.9336.
13C NMR (CDCl3, 100 MHz) δ 15.0, 21.4, 26.9, 127.7, 128.3,
128.4, 128.8, 129.6, 132.3, 134.4, 136.6, 137.0, 141.3; MS (EI,
m/z) 254 (M+, 100), 225 (63), 210 (58), 192 (14), 178 (12); HRMS
General procedure for the Suzuki coupling of 3
To a mixture of 4a (79 mg, 0.65 mmol), Pd(OAc)2 (5.6 mg, (EI) calcd for C17H18S (M+) 254.1129, found 254.1127.
0.025 mmol), Cs2CO3 (244 mg, 0.75 mmol), and PPh3
Compound 5g. 90% yield (133 mg), colorless oil; 1H NMR
(13.1 mg, 0.05 mmol) in 2 mL of THF was added 3a (99 mg, (CDCl3, 400 MHz) δ 1.13 (t, J = 7.4 Hz, 3H), 1.38 (s, 9H), 2.48
0.5 mmol) under a nitrogen atmosphere. After stirring at 40 °C (q, J = 7.4 Hz, 2H), 6.84 (s, 1H), 7.35–7.37 (m, 1H), 7.40–7.46
for 5 h, the reaction mixture was quenched with water, (m, 4H), 7.62–7.65 (m, 2H), 7.74 (d, J = 8.4 Hz, 2H); 13C NMR
extracted with ethyl acetate, washed with brine, dried over (CDCl3, 100 MHz) δ 15.0, 27.0, 31.3, 34.7, 125.0, 127.7, 128.3,
Na2SO4, and concentrated. Column chromatography on silica 128.3, 128.4, 129.4, 132.2, 134.3, 141.4, 150.2; MS (EI, m/z) 296
gel (petroleum ether/EtOAc = 50/1) gave 109 mg (91%) of 5a as (M+, 74), 281 (86), 239 (40); HRMS (EI) calcd for C20H24S (M+)
a colorless oil. 5a could also be prepared from 3r in 87% yield 296.1599, found 296.1592.
1
(104 mg). H NMR (CDCl3, 400 MHz) δ 1.13 (t, J = 7.4 Hz, 3H),
Compound 5h. 89% yield (120 mg), colorless oil; 1H NMR
2.49 (q, J = 7.4 Hz, 2H), 6.87 (s, 1H), 7.28–7.37 (m, 1H), (CDCl3, 400 MHz) δ 1.15 (t, J = 7.4 Hz, 3H), 2.50 (q, J = 7.4 Hz,
7.39–7.46 (m, 5H), 7.65 (d, J = 9.2 Hz, 2H), 7.76 (d, J = 8.0 Hz, 2H), 3.87 (s, 3H), 6.85 (s, 1H), 6.98 (d, J = 8.8 Hz, 2H),
2H); 13C NMR (CDCl3, 100 MHz) δ 14.9, 26.9, 127.1, 127.8, 7.36–7.40 (m, 1H), 7.41–7.45 (m, 2H), 7.65–7.67 (m, 2H), 7.78
128.0, 128.2, 128.3, 129.6, 132.1, 137.1, 137.6, 141.1; MS (EI, (d, J = 8.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 14.9, 26.8,
m/z) 240 (M+, 96), 211 (100), 178 (66), 164 (11); HRMS (EI) 55.1, 113.3, 127.5, 128.1, 128.2, 129.8, 130.9, 131.9, 135.0,
calcd for C16H16S (M+) 240.0973, found 240.0976.
141.3, 158.6; MS (EI, m/z) 270 (M+, 100), 241 (56), 226 (34), 210
1
Compound 5b.18 84% yield (121 mg), colorless oil; H NMR (15); HRMS (EI) calcd for C17H18OS (M+) 270.1078, found
(CDCl3, 400 MHz) δ 7.08–7.11 (m, 1H), 7.15–7.22 (m, 2H), 270.1083.
7.25–7.40 (m, 7H), 7.45 (dd, J = 10.5, 4.7 Hz, 2H), 7.71–7.78 (m,
Compound 5i. 94% yield (141 mg), colorless oil; 1H NMR
2H), 7.84 (d, J = 7.5 Hz, 2H); 13C NMR (CDCl3, 100 MHz) (CDCl3, 400 MHz) δ 1.12 (t, J = 7.4 Hz, 3H), 2.47 (q, J = 7.4 Hz,
δ 125.9, 127.9, 128.0, 128.1, 128.3, 128.3, 128.8, 129.2, 129.6, 2H), 3.91 (s, 3H), 3.95 (s, 3H), 6.79 (s, 1H), 6.89 (d, J = 8.4 Hz,
134.8, 135.3, 135.8, 136.8, 141.0.
1H), 7.25–7.34 (m, 2H), 7.39 (t, J = 7.2 Hz, 2H), 7.56–7.63 (m,
Compound 5c. 87% yield (112 mg), colorless oil; 1H NMR 3H); 13C NMR (CDCl3, 100 MHz) δ 15.1, 27.0, 55.9, 55.9, 110.7,
(CDCl3, 400 MHz) δ 1.10 (t, J = 7.4 Hz, 3H), 2.46 (q, J = 7.4 Hz, 112.6, 123.1, 127.7, 128.3, 128.4, 130.2, 132.2, 135.3, 141.4,
2H), 6.79 (s, 1H), 7.06–7.11 (m, 2H), 7.35–7.40 (m, 1H), 148.3, 148.3; MS (EI, m/z) 300 (M+, 70), 271 (66), 240 (100), 225
7.41–7.43 (m, 2H), 7.60–7.62 (m, 2H), 7.70–7.74 (m, 2H); (44); HRMS (EI) calcd for C18H20O2S (M+) 300.1184, found
13C NMR (CDCl3, 100 MHz) δ 15.0, 26.9, 115.0 (d, J = 21.2 Hz), 300.1186.
127.9, 128.3, 128.4, 131.0, 131.3 (d, J = 7.9 Hz), 133.2 (d, J =
Compound 5j. 82% yield (119 mg), colorless oil; 1H NMR
3.3 Hz), 137.3, 141.0, 161.7 (d, J = 245.9 Hz); MS (EI, m/z) (CDCl3, 400 MHz) δ 1.19 (t, J = 7.4 Hz, 3H), 2.56 (q, J = 7.4 Hz,
258 (M+, 100), 229 (54), 196 (30), 183 (8); HRMS (EI) calcd for 2H), 7.07 (s, 1H), 7.42–7.55 (m, 5H), 7.73–7.75 (m, 2H),
C16H15FS (M+) 258.0878, found 258.0883.
7.90–7.95 (m, 3H), 8.02 (d, J = 8.8 Hz, 1H), 8.22 (s, 1H);
Compound 5d. It was prepared from 3d and 3s in respective 13C NMR (CDCl3, 100 MHz) δ 15.1, 27.1, 126.1, 126.2, 127.5,
yields of 86% (118 mg) and 83% (114 mg) as a colorless oil; 127.7, 127.7, 128.0, 128.3, 128.4, 128.5, 129.0, 132.3, 132.6,
1H NMR (CDCl3, 400 MHz) δ 1.12 (t, J = 7.4 Hz, 3H), 2.48 (q, J = 133.4, 134.8, 138.2, 141.3; HRMS (ESI) calcd for C20H18S (M+)
7.4 Hz, 2H), 6.79 (s, 1H), 7.36–7.39 (m, 3H), 7.44 (t, J = 6.8 Hz, 290.1129, found 290.1134.
2H), 7.63 (d, J = 7.6 Hz, 2H), 7.70 (d, J = 8.4 Hz, 2H); 13C NMR
Compound 5k. 85% yield (122 mg), colorless oil, Z/E > 95/5;
(CDCl3, 100 MHz) δ 15.0, 27.0, 128.0, 128.1, 128.2, 128.4, 1H NMR (CDCl3, 400 MHz) δ 0.93 (t, J = 6.7 Hz, 3H), 1.10 (t, J =
130.7, 130.9, 132.6, 135.5, 138.5, 140.9; MS (EI, m/z) 276 (2), 7.3 Hz, 3H), 1.29–1.43 (m, 14H), 2.41 (q, J = 7.3 Hz, 2H), 2.49
274 (M+, 7), 247 (48), 245 (100), 210 (11); HRMS (EI) calcd for (q, J = 7.2 Hz, 2H), 6.04 (t, J = 7.2 Hz, 1H), 7.29 (t, J = 7.4 Hz,
C16H15ClS (M+) 274.0583, found 274.0583.
1H), 7.36 (dd, J = 10.2, 4.6 Hz, 2H), 7.51–7.59 (m, 2H); 13C
Compound 5e. 79% yield (126 mg), colorless oil; 1H NMR NMR (CDCl3, 100 MHz) δ 14.2, 15.1, 22.7, 26.1, 29.0, 29.4, 29.5,
(CDCl3, 400 MHz) δ 1.10 (t, J = 7.4 Hz, 3H), 2.46 (q, J = 7.4 Hz, 29.6, 29.7, 30.6, 32.0, 127.3, 127.9, 128.2, 135.4, 136.4, 140.7;
2H), 6.75 (s, 1H), 7.36–7.40 (m, 1H), 7.41–7.42 (m, 2H), HRMS (ESI) calcd for C19H30S (M+) 290.2068, found 290.2072.
7.50–7.53 (m, 2H), 7.59–7.63 (m, 4H); 13C NMR (CDCl3,
Compound 5l. 89% yield (123 mg), colorless oil, E/Z > 95/5;
100 MHz) δ 15.0, 27.0, 120.9, 128.1, 128.3, 128.5, 130.8, 131.1, 1H NMR (CDCl3, 400 MHz) δ 0.86–0.95 (m, 6H), 1.06 (t, J =
131.2, 136.0, 138.7, 140.9; MS (EI, m/z) 320 (1), 318 (M+, 1), 7.3 Hz, 3H), 1.23–1.41 (m, 6H), 1.44–1.56 (m, 2H), 2.36 (q, J =
291 (8), 289 (11), 210 (100); HRMS (EI) calcd for C16H15BrS 7.3 Hz, 2H), 2.75–2.95 (m, 1H), 5.72 (d, J = 9.8 Hz, 1H),
(M+) 318.0078, found 318.0072.
7.24–7.31 (m, 1H), 7.35 (t, J = 7.4 Hz, 2H), 7.48–7.60 (m, 2H);
Compound 5f. It was prepared from 3f and 3t in respective 13C NMR (CDCl3, 100 MHz) δ 12.0, 14.1, 15.2, 22.9, 26.0, 28.7,
yields of 85% (108 mg) and 87% (110 mg) as a colorless oil; 1H 29.7, 35.2, 41.8, 127.3, 127.9, 128.2, 135.5, 140.7, 141.7; HRMS
NMR (CDCl3, 400 MHz) δ 1.13 (t, J = 7.4 Hz, 3H), 2.42 (s, 3H), (ESI) calcd for C17H26S (M+) 262.1755, found 262.1750.
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Compound 5m. 71% yield (94 mg), colorless oil; 1H NMR
Organic & Biomolecular Chemistry
Compound 5t. 81% yield (117 mg), colorless oil; 1H NMR
(CDCl3, 600 MHz) δ 1.24 (t, J = 7.6 Hz, 3H), 2.76 (q, J = 7.6 Hz, (CDCl3, 400 MHz) δ 1.12 (t, J = 7.3 Hz, 3H), 2.49 (q, J = 7.3 Hz,
2H), 7.02 (d, J = 15.5 Hz, 1H), 7.07 (s, 1H), 7.25 (d, J = 15.5 Hz, 2H), 6.99 (s, 1H), 7.26–7.56 (m, 6H), 7.79–7.96 (m, 5H), 8.08 (s,
1H), 7.31–7.36 (m, 2H), 7.39–7.48 (m, 4H), 7.56 (d, J = 7.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 15.1, 27.1, 126.2, 126.4,
2H), 7.88 (d, J = 7.8 Hz, 2H); 13C NMR (CDCl3, 150 MHz) δ 126.5, 127.1, 127.3, 127.7, 128.0, 128.1, 128.2, 129.7, 132.7,
14.8, 27.9, 126.7, 127.6, 127.7, 128.0, 128.7, 129.9, 131.4, 131.6, 133.0, 133.4, 137.2, 137.6, 138.7; HRMS (ESI) calcd for
133.8, 136.5, 136.7, 137.0; HRMS (ESI) calcd for C18H18S (M+) C20H18S, (M+) 290.1129, found 290.1134.
266.1129, found 266.1125.
Compound 5u. 76% yield (93 mg), colorless oil; 1H NMR
Compound 5n. 93% yield (118 mg), colorless oil; 1H NMR (CDCl3, 600 MHz) δ 1.30 (t, J = 7.4 Hz, 3H), 2.78 (q, J = 7.3 Hz,
(CDCl3, 400 MHz) δ 1.16 (t, J = 7.4 Hz, 3H), 2.43–2.56 (m, 5H), 2H), 7.11–7.18 (m, 1H), 7.26 (s, 1H), 7.37–7.40 (m, 2H),
6.88 (s, 1H), 7.21–7.37 (m, 3H), 7.45 (t, J = 7.7 Hz, 2H), 7.58 (d, 7.43–7.54 (m, 3H), 7.91 (d, J = 7.4 Hz, 2H); 13C NMR (CDCl3,
J = 8.0 Hz, 2H), 7.80 (d, J = 7.6 Hz, 2H); 13C NMR (CDCl3, 150 MHz) δ 14.8, 27.9, 125.4, 125.4, 127.3, 127.4, 128.0, 129.0,
100 MHz) δ 15.1, 21.3, 27.0, 127.1, 128.1, 128.2, 129.2, 129.7, 129.6, 132.1, 136.5, 146.3; MS (EI, m/z) 247 (3), 246 (M+, 26),
131.6, 137.3, 137.6, 137.7, 138.3; MS (EI, m/z) 255 (30), 254 217 (25), 185 (39); HRMS (EI) calcd for C14H14S2 (M+) 246.0537,
(M+, 100), 226 (25), 225 (98), 193 (26); HRMS (EI) calcd for found 246.0539.
C17H18S (M+) 254.1129, found 254.1126.
Compound 5v. 75% yield (86 mg), yellow oil; 1H NMR
Compound 5o. 86% yield (109 mg), colorless oil; 1H NMR (CDCl3, 600 MHz) δ 1.23 (t, J = 7.6 Hz, 3H), 2.75 (q, J = 7.6 Hz,
(CDCl3, 400 MHz) δ 1.33 (t, J = 7.4 Hz, 3H), 2.45–2.50 (m, 5H), 2H), 6.52 (d, J = 1.7 Hz, 1H), 6.77 (d, J = 5.2 Hz, 1H), 7.34 (t, J =
6.85 (s, 1H), 7.19 (d, J = 7.3 Hz, 1H), 7.29–7.32 (m, 2H), 7.4 Hz, 1H), 7.42–7.47 (m, 3H), 7.51 (s, 1H), 7.91 (d, J = 7.8 Hz,
7.40–7.46 (m, 4H), 7.76 (d, J = 7.4 Hz, 2H); 13C NMR (CDCl3, 2H); 13C NMR (CDCl3, 151 MHz) δ 14.7, 28.2, 109.4, 111.6,
100 MHz) δ 15.0, 21.5, 27.0, 125.5, 127.1, 128.1, 128.3, 128.7, 124.0, 127.6, 128.0, 129.8, 131.2, 136.3, 142.5, 154.5; HRMS
129.0, 129.7, 131.9, 137.2, 137.7, 138.0, 141.1; MS (EI, m/z) 255 (EI) calcd for C14H14OS (M+) 230.0765, found 230.0758.
(3), 254 (M+, 21), 226 (4), 225 (31), 193 (6); HRMS (EI) calcd for
C17H18S (M+) 254.1129, found 254.1122.
Compound 5w. 66% yield (59 mg), colorless oil; 1H NMR
(CDCl3, 400 MHz) δ 1.30 (t, J = 7.4 Hz, 3H), 2.27 (s, 3H), 2.85
Compound 5p. 62% yield (79 mg), colorless oil; 1H NMR (q, J = 7.4 Hz, 2H), 6.52 (s, 1H), 7.23 (t, J = 7.2 Hz, 1H), 7.37 (t,
(CDCl3, 600 MHz) δ 1.11 (t, J = 7.4 Hz, 3H), 2.31 (q, J = 7.4 Hz, J = 7.5 Hz, 2H), 7.55 (d, J = 7.8 Hz, 2H); 13C NMR (CDCl3,
2H), 2.48 (s, 3H), 6.50 (s, 1H), 7.22–7.35 (m, 5H), 7.43 (t, J = 100 MHz) δ 15.1, 24.7, 25.2, 126.4, 127.3, 128.0, 129.1, 132.7,
7.7 Hz, 2H), 7.69 (d, J = 7.7 Hz, 2H); 13C NMR (CDCl3, 137.2; MS (EI, m/z) 179 (1), 178 (M+, 11), 150 (5), 149 (15), 117
150 MHz) δ 14.8, 19.8, 26.4, 125.6, 126.8, 127.7, 128.1, 128.6, (22); HRMS (EI) calcd for C11H14S (M+) 178.0816, found
129.3, 129.6, 130.2, 136.3, 137.0, 137.7, 140.2; MS (EI, m/z) 255 178.0818.
(14), 254 (M+, 100), 226 (17), 225 (100), 193 (14); HRMS (EI)
General procedure for the Negishi coupling of 3a
calcd for C17H18S (M+) 254.1129, found 254.1129.
Compound 5q. 89% yield (120 mg), colorless oil; 1H NMR To a solution of 3a (99 mg, 0.5 mmol) and Pd(PPh3)4 (29 mg,
(CDCl3, 400 MHz) δ 1.14 (t, J = 7.2 Hz, 3H), 2.50 (dd, J = 14.4, 0.025 mmol) in anhydrous THF (1 mL) and NMP (1 mL) was
7.2 Hz, 2H), 3.88 (s, 3H), 6.83 (s, 1H), 6.98 (d, J = 8.3 Hz, 2H), added PhZnBr (0.75 mmol) at room temperature. After stirring
7.30 (t, J = 7.0 Hz, 1H), 7.43 (t, J = 7.3 Hz, 2H), 7.60 (d, J = at 50 °C for 3 h, the reaction mixture was quenched with
8.3 Hz, 2H), 7.78 (d, J = 7.5 Hz, 2H); 13C NMR (CDCl3, water, extracted with EtOAc, washed with brine, dried over
100 MHz) δ 15.1, 27.0, 55.4, 113.8, 127.0, 128.1, 129.5, 129.6, Na2SO4 and concentrated. Column chromatography on silica
131.2, 133.6, 137.2, 137.4, 159.5; HRMS (ESI) calcd for gel (petroleum ether/EtOAc = 50/1) gave 86 mg (72%) of 5a as a
C17H18OS (M+) 270.1078, found 270.1079.
colorless oil. The spectra data are in good agreement with
Compound 5r. 86% yield (129 mg), colorless oil; 1H NMR those obtained above.
(CDCl3, 400 MHz) δ 1.11 (t, J = 7.4 Hz, 3H), 2.48 (q, J = 7.4 Hz,
General procedure for the Sonogashira coupling of 3a
2H), 3.90–395 (m, 6H), 6.81 (s, 1H), 6.89 (d, J = 8.3 Hz, 1H),
7.15–7.40 (m, 5H), 7.73 (d, J = 8.3 Hz, 2H); 13C NMR (CDCl3, To a mixture of 3a (99 mg, 0.5 mmol), PdCl2 (4.4 mg,
100 MHz) δ 15.1, 27.0, 55.9, 56.0, 110.8, 111.4, 120.7, 127.0, 0.025 mmol), CuI (9.5 mg, 0.05 mmol), PPh3 (13.1 mg,
128.0, 129.6, 131.2, 134.0, 137.2, 137.3, 148.7, 148.9; HRMS 0.05 mmol), and Cs2CO3 (326 mg, 1.0 mmol) in 2 mL of THF
(ESI) calcd for C18H20O2S (M+) 300.1184, found 300.1188.
was added phenylacetylene (102 mg, 1.0 mmol). After stirring
Compound 5s. 80% yield (103 mg), colorless oil; 1H NMR at room temperature for 8 h, the reaction mixture was
(CDCl3, 600 MHz) δ 1.15 (t, J = 7.4 Hz, 3H), 2.49 (q, J = 7.3 Hz, quenched with water, extracted with EtOAc, washed with
2H), 6.85 (s, 1H), 7.15 (t, J = 8.6 Hz, 2H), 7.33 (t, J = 7.3 Hz, brine, dried over Na2SO4 and concentrated. Column chromato-
1H), 7.45 (t, J = 7.7 Hz, 2H), 7.64 (dd, J = 8.3, 5.6 Hz, 2H), 7.79 graphy on silica gel (petroleum ether/EtOAc = 50/1) gave
(d, J = 7.8 Hz, 2H); 13C NMR (CDCl3, 150 MHz) δ 15.0, 27.0, 111 mg (84%) of 5x as a colorless oil. 1H NMR (CDCl3,
115.3 (d, J = 21.2 Hz), 127.3, 128.1, 129.7, 129.9 (d, J = 7.9 Hz), 400 MHz) δ 1.47 (t, J = 7.4 Hz, 3H), 3.18 (q, J = 7.4 Hz, 2H), 7.15
132.4, 136.5, 137.0, 137.3 (d, J = 3.0 Hz), 162.5 (d, J = 246.0 Hz); (s, 1H), 7.33–7.35 (m, 1H), 7.41–7.47 (m, 5H), 7.57–7.60 (m,
MS (EI, m/z) 259 (11), 258 (M+, 61), 230 (15), 229 (76), 228 (14); 2H), 7.71 (d, J = 8.0 Hz, 2H); 13C NMR (CDCl3, 100 MHz)
HRMS (EI) calcd for C16H15FS (M+) 258.0878, found 258.0878.
δ 15.5, 27.8, 87.3, 92.1, 119.1, 123.0, 127.7, 128.3, 128.5, 128.6,
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129.7, 131.6, 134.8, 136.2; MS (EI, m/z): 264 (M+, 12), 235 (15), 179 (100), 165 (74), 152 (51); HRMS (EI) calcd for C17H18O2
215 (86), 202 (40), 189 (100); HRMS (EI) calcd for C18H16S (M+) (M+) 254.1307, found 254.1305.
264.0973, found 264.0976.
Compound 7g. 78% yield (48 mg), white solid, mp
Compound 5y. 81% yield (105 mg), colorless oil; 1H NMR 112–113 °C; H NMR (CDCl3, 400 MHz) δ 2.41 (s, 3H), 7.04 (s,
(CDCl3, 400 MHz) δ 0.28 (s, 9H), 1.35 (t, J = 7.4 Hz, 3H), 3.02 1H), 7.35–7.37 (m, 1H), 7.44 (t, J = 7.6 Hz, 2H), 7.51–7.56 (m,
(q, J = 7.4 Hz, 2H), 7.01 (s, 1H), 7.18–7.30 (m, 1H), 7.37 (t, J = 3H), 7.62 (d, J = 7.2 Hz, 2H), 7.87–7.89 (m, 4H); 13C NMR
7.8 Hz, 2H), 7.52–7.62 (m, 2H); 13C NMR (CDCl3, 100 MHz) (CDCl3, 100 MHz) δ 17.7, 125.8, 126.1, 126.1, 126.1, 127.3,
δ −0.1, 15.5, 27.7, 97.3, 101.8, 119.0, 127.6, 128.2, 129.6, 135.1, 127.7, 127.8, 127.8, 128.0, 128.4, 128.4, 132.2, 133.4, 135.9,
136.0; HRMS (ESI) calcd for C15H20SSi (M+), 260.1055, found 137.9, 144.0; MS (EI, m/z) 244 (M+, 14), 229 (18), 215 (31), 165
1
260.1048.
(100); HRMS (EI) calcd for C19H16 (M+) 244.1252, found
244.1258.
General procedure for the synthesis of 7
Compound 7h. 71% yield (43 mg), yellow oil; 1H NMR
To a mixture of 5a (60 mg, 0.25 mmol) and Ni(PPh3)2Cl2 (CDCl3, 600 MHz) δ 0.91 (t, J = 7.0 Hz, 3H), 1.21–1.47 (m, 14H),
(16.3 mg, 0.025 mmol) in 2 mL of THF was added the 6a 2.05 (s, 3H), 2.19–2.23 (m, 2H), 5.79–5.82 (m, 1H), 7.24 (d, J =
(0.75 mmol) under a nitrogen atmosphere. After stirring for 7.3 Hz, 1H), 7.31–7.34 (m, 2H), 7.40–7.41 (m, 2H); 13C NMR
12 h at room temperature, the reaction mixture was quenched (CDCl3, 150 MHz) δ 14.1, 15.8, 22.7, 28.8, 29.3, 29.4, 29.6, 29.6,
with water, extracted with EtOAc, washed with brine, dried 29.6, 31.9, 125.6, 126.4, 128.1, 128.9, 134.5, 144.1; MS (EI, m/z)
over Na2SO4 and concentrated. Column chromatography on 245 (2), 244 (M+, 8), 132 (13), 131 (100), 130 (8), 129 (15), 118
silica gel (petroleum ether/Et2O = 100/1) gave 42 mg (86%) of (93); HRMS (EI) calcd for C18H28 (M+) 244.2191, found
7a22 as a white solid, mp 81–82 °C. It was also prepared from 244.2198.
5b in 76% yield (37 mg) as a white solid; 1H NMR (CDCl3,
Compound 7i.26 89% yield (46 mg), white solid, mp
400 MHz) δ 2.35 (s, 3H), 6.91 (s, 1H), 7.31–7.37 (m, 2H), 72–73 °C; 1H NMR (CDCl3, 400 MHz) δ 2.25 (d, J = 1.3 Hz, 3H),
7.42–7.45 (m, 6H), 7.58–7.60 (m, 2H); 13C NMR (CDCl3, 2.35 (s, 3H), 6.81 (d, J = 1.0 Hz, 1H), 7.16 (d, J = 8.0 Hz, 2H),
100 MHz) δ 17.5, 126.0, 126.5, 127.2, 127.8, 128.2, 128.4, 129.2, 7.20–7.23 (m, 1H), 7.34 (d, J = 4.6 Hz, 4H), 7.41 (d, J = 8.2 Hz,
137.5, 138.4, 144.0.
Compound 7b.24 75% yield (40 mg), white solid, mp 127.0, 128.2, 129.1, 129.2, 137.0, 137.3, 138.6, 141.2.
2H); 13C NMR (CDCl3, 100 MHz) δ 17.5, 21.2, 126.0, 126.4,
85–86 °C; 1H NMR (CDCl3, 400 MHz) δ 2.29 (d, J = 1.2 Hz, 3H),
Compound 7j. 75% yield (39 mg), white solid, mp 65–67 °C;
6.82 (s, 1H), 7.10 (t, J = 8.8 Hz, 2H), 7.33–7.43 (m, 5H), 7.56 (d, 1H NMR (CDCl3, 400 MHz) δ 2.29 (s, 3H), 2.41 (s, 3H), 6.84 (s,
J = 9.2 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 17.5, 115.1 (d, J = 1H), 7.10–7.14 (m, 1H), 7.26–7.33 (m, 2H), 7.35–7.40 (M, 6H);
21.1 Hz), 126.0, 126.6, 127.3, 128.4, 130.7 (d, J = 7.8 Hz), 134.4 13C NMR (CDCl3, 100 MHz) δ 17.6, 21.6, 123.2, 126.4, 126.8,
(d, J = 3.4 Hz), 137.4, 143.8, 161.4 (d, J = 244.5 Hz).
127.5, 127.9, 128.1, 128.2, 129.2, 137.6, 137.9, 138.4, 144.0;
Compound 7c.25 80% yield (42 mg), white solid, mp HRMS (ESI) calcd for C16H16 (M+) 208.1252, found 208.1255.
48–50 °C; 1H NMR (CDCl3, 400 MHz) δ 2.32 (d, J = 1.2 Hz, 3H),
Compound 7k.27 82% yield (46 mg), white solid, mp
2.40 (s, 3H), 6.85 (s, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.30–7.33 (m, 95–96 °C; 1H NMR (CDCl3, 400 MHz) δ 2.28 (s, 3H), 3.85 (s,
3H), 7.40 (t, J = 7.2 Hz, 2H), 7.54–7.57 (m, 2H); 13C NMR 3H), 6.80 (s, 1H), 6.88–6.98 (m, 2H), 7.21–7.30 (m, 1H),
(CDCl3, 100 MHz) δ 17.5, 21.2, 126.0, 127.1, 127.7, 128.3, 7.35–7.42 (m, 4H), 7.44–7.52 (m, 2H); 13C NMR (CDCl3,
128.9, 129.1, 135.5, 136.2, 136.7, 144.2.
Compound 7d. 81% yield (51 mg), white solid, mp 136.4, 136.8, 138.6, 159.0.
73–74 °C; 1H NMR (CDCl3, 400 MHz) δ 1.45 (s, 9H), 2.40 (s,
Compound 7l. 80% yield (51 mg), yellow solid, mp
100 MHz) δ 17.5, 55.4, 113.7, 126.2, 126.3, 127.1, 128.2, 129.1,
1
3H), 6.92 (s, 1H), 7.41–7.51 (m, 7H), 7.62 (t, J = 7.6 Hz, 2H); 134–136 °C; H NMR (CDCl3, 400 MHz) δ 2.28 (s, 3H), 3.92 (s,
13C NMR (CDCl3, 100 MHz) δ 17.6, 31.5, 34.6, 125.2, 126.1, 3H), 3.96 (s, 3H), 6.81 (s, 1H), 6.89 (d, J = 8.0 Hz, 1H),
127.1, 127.7, 128.4, 129.0, 135.6, 136.9, 144.3, 149.5; MS (EI, 7.09–7.11 (m, 2H), 7.26–7.27 (m, 1H), 7.37–7.39 (m, 4H); 13C
m/z) 250 (M+, 39), 235 (100), 193 (11), 178 (18), 115 (30); HRMS NMR (CDCl3, 100 MHz) δ 17.6, 55.9, 56.0, 109.4, 111.0, 118.4,
(EI) calcd for C19H22 (M+) 250.1722, found 250.1718.
126.4, 126.6, 128.2, 129.1, 136.9, 137.1, 138.5, 148.5, 148.7; MS
Compound 7e.26 80% yield (45 mg), white solid, mp (EI, m/z) 254 (M+, 100), 224 (57), 179 (61), 165 (47), 152 (39);
85–86 °C; 1H NMR (CDCl3, 400 MHz) δ 2.29 (s, 3H), 3.85 (s, HRMS (EI) calcd for C17H18O2 (M+) 254.1307, found 254.1310.
3H), 6.79 (s, 1H), 6.93 (d, J = 8.4 Hz, 2H), 7.26–7.40 (m, 5H),
Compound 7m.26 87% yield (53 mg), white solid, mp
7.53 (d, J = 7.6 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 17.5, 146–148 °C; H NMR (CDCl3, 400 MHz) δ 2.42 (d, J = 1.2 Hz,
1
55.3, 113.6, 126.0, 127.0, 127.3, 128.3, 130.4, 131.0, 135.9, 3H), 7.04 (s, 1H), 7.23–7.35 (m, 1H), 7.42–7.51 (m, 6H),
144.2, 158.2.
7.73–7.76 (m, 1H), 7.85–7.90 (m, 3H), 7.97 (s, 1H); 13C NMR
Compound 7f. 84% yield (53 mg), white solid, mp (CDCl3, 100 MHz) δ 17.5, 124.4, 124.7, 125.8, 126.2, 126.6,
1
153–154 °C; H NMR (CDCl3, 400 MHz) δ 2.32 (s, 3H), 3.92 (s, 127.6, 127.8, 128.2, 128.2, 128.3, 129.3, 132.7, 133.5, 137.2,
6H), 6.80 (s, 1H), 6.91–6.96 (m, 3H), 7.36–7.38 (m, 3H), 7.53 (d, 138.4, 141.1.
J = 7.2 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 17.6, 55.9, 55.9,
Compound 7n. 61% yield (51 mg), yellow oil; 1H NMR
111.0, 112.5, 121.7, 126.0, 127.0, 127.5, 128.3, 131.3, 136.3, (CDCl3, 400 MHz) δ 0.90 (t, J = 7.1 Hz, 3H), 1.24–1.36 (m, 14H),
144.1, 147.8, 148.6; MS (EI, m/z) 254 (M+, 78), 224 (17), 2.14 (q, J = 7.3 Hz, 2H), 3.88 (s, 3H), 6.05 (t, J = 7.4 Hz, 1H),
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6.92 (d, J = 8.3 Hz, 2H), 7.11 (d, J = 8.3 Hz, 2H), 7.21–7.28 (m,
5H); 13C NMR (CDCl3, 150 MHz) δ 14.1, 22.7, 29.3, 29.3, 29.5,
29.6, 29.8, 30.0, 31.9, 55.2, 113.5, 126.7, 127.3, 128.0, 130.2,
131.1, 132.7, 141.0, 143.4, 158.5; HRMS (ESI) calcd for C24H32O
(M+) 336.2453, found 336.2459.
4 (a) H. M. Weiss, K. M. Touchette, S. Angell and J. Khan,
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Compound 7o.23 71% yield (34 mg), white solid, mp
48–49 °C; 1H NMR (CDCl3, 400 MHz) δ 2.25 (s, 3H), 6.51 (s,
1H), 6.98 (d, J = 7.2 Hz, 2H), 7.09–7.15 (m, 3H), 7.22 (d, J =
7.6 Hz, 2H), 7.28–7.33 (m, 3H); 13C NMR (CDCl3, 100 MHz)
δ 27.2, 126.1, 126.6, 126.9, 127.9, 128.2, 128.5, 129.0, 137.6,
138.8, 142.1.
Compound 7p. 65% yield (49 mg), white solid, mp
211–213 °C; 1H NMR (CDCl3, 600 MHz) δ 3.89 (s, 3H),
6.91–6.97 (m, 3H), 7.06 (t, J = 8.7 Hz, 2H), 7.14–7.23 (m, 7H),
7.35–7.38 (m, 2H); 13C NMR (CDCl3, 150 MHz) δ 55.2, 114.2,
115.1 (d, J = 21.5 Hz), 126.7, 127.7, 128.1, 129.4 (d, J = 8.2 Hz),
129.5, 131.7, 132.4, 137.6, 140.0 (d, J = 2.8 Hz), 141.3, 159.2,
162.5 (d, J = 245.8 Hz); MS (EI, m/z) 305 (22), 304 (M+, 100), 203
5 P. J. Stang and K. A. Roberts, J. Org. Chem., 1987, 52, 5213
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(M+) 304.1263, found 304.1266.
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1
190–192 °C; H NMR (CDCl3, 600 MHz) δ 2.47 (s, 3H), 6.97 (s,
130.
1H), 7.04–7.10 (m, 2H), 7.13–7.25 (m, 9H), 7.36–7.41 (m, 2H); 12 For a review, see: E. Negishi, Z. Huang, G. Wang, S. Mohan,
13C NMR (CDCl3, 150 MHz) δ 21.4, 115.0, 115.2, 126.8, 127.8,
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(16); HRMS (EI) calcd for C21H17F (M+) 288.1314, found
288.1316.
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Acknowledgements
We acknowledge financial support from the National Natural
Science Foundation of China (Nos 20902084 and 21172199),
the Natural Science Foundation of Zhejiang Province
(LR12B02001), the Program for Changjiang Scholars and Inno-
vative Research Team in Chinese Universities (IRT0980), and
Zhejiang Normal University.
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