Stereoselective synthesis of polyfunctional tetrasubstituted alkenyl sulfides via a carbocupration of alkynyl sulfides with aryl and benzylic diorganozincs

Article abstract of DOI:10.1055/s-0030-1260210

A general method for the synthesis of tetrasubstituted alkenyl sulfides has been developed by the carbocupration of alkynyl sulfides with functionalized diorganozinc reagents in the presence of CuCN·2LiCl. The intermediate alkenylcopper reagents readily r

Full text of DOI:10.1055/s-0030-1260210

PAPER
3453
Stereoselective Synthesis of Polyfunctional Tetrasubstituted Alkenyl Sulfides
via a Carbocupration of Alkynyl Sulfides with Aryl and Benzylic
Diorganozincs
S
ynthesis of Tetr
o
r
A
lkenyl
a
Sulfides Dunst,a Albrecht Metzger,a Elena A. Zaburdaeva,a,b Paul Knochel*a
a
Ludwig-Maximilians-Universität München, Department Chemie, Butenandtstr. 5-13, Haus F, 81377 München, Germany
Fax +49(89)218077680; E-mail: paul.knochel@cup.uni-muenchen.de
Lobachevsky State University of Nizhni Novgorod, Chemistry Department, 23 Prospekt Gagarina, 603950, Nizhni Novgorod,
b
Russian Federation
Fax +7(831)4623085; E-mail: zaea4@rambler.ru
Received 29 July 2011
nesium insertion into aryl bromides of type 4 in the
presence of zinc chloride (0.55 equiv; method A)7d,e or by
I/Mg-exchange using isopropylmagnesium chloride–lith-
ium chloride9 as in the case of the aryl iodides 5a and 5b
Abstract: A general method for the synthesis of tetrasubstituted
alkenyl sulfides has been developed by the carbocupration of alkyn-
yl sulfides with functionalized diorganozinc reagents in the pres-
ence of CuCN·2LiCl. The intermediate alkenylcopper reagents
readily react with various electrophiles furnishing a broad range of followed by transmetalation with zinc chloride (0.55
highly functionalized alkenes with excellent stereoselectivity (E/Z
93:7–99:1).
equiv; method B). The resulting alkenylcopper reagents
3a–h reacted with various electrophiles affording alkenyl
sulfides 6a–p in 57–91% yield and E/Z ratios >93:7. Some
loss of stereoselectivity was however observed during the
quenching step.
Key words: alkynyl sulfides, copper, zinc, carbometalation, olefins
The stereoselective synthesis of tetrasubstituted olefins is
of high interest, since these carbon fragments are present
in many natural products and drugs like Tamoxifen.1 The
carbometalation of substituted alkynes constitutes an ex-
cellent stereoselective synthesis of such unsaturated mol-
ecules.2 A variety of carbometalation reactions using
copper, magnesium, boron, and tin reagents have been re-
ported.3 Recently, the stereoselective carbometalation of
alkynes using organozinc reagents and catalytic amounts
of cobalt dibromide was also described.4 Organometallic
zinc compounds are important reagents in organic synthe-
sis, due to their high functional group compatibility.5 Fur-
thermore, they can be transmetalated with copper(I) salts
providing organocopper reagents that readily undergo
carbometalation reactions.6
method A:
R
R
Mg (2.5 equiv)
LiCl (0.75 equiv)
ZnCl2 (0.55 equiv)
THF, 25 °C
2
Zn·2MgX2·LiCl
Br
4: R = Cl, NMe2, OMe
2a,c,d,g,h
X = Cl, Br
method B:
EtO2C
1) i-PrMgCl·LiCl (1.1 equiv)
THF, –20 °C, 30 min
EtO2C
2) ZnCl2 (0.55 equiv)
–20 °C, 30 min
2
I
Zn·2MgX2·2LiCl
5a: 3-CO2Et
5b: 4-CO2Et
2e: 3-CO2Et
2f: 4-CO2Et
Herein, we wish to report a new approach to the stereose-
lective carbocupration of alkynes using highly functional-
ized aryl or benzylic diorganozinc reagents7 and
stoichiometric amounts of copper(I) cyanide–di(lithium
chloride) (CuCN·2LiCl).8 Various functional groups can
be tolerated in the alkynyl side chain, such as cyanide,
dimethylamino group, or bromide. Thus, the readily pre-
pared alkynyl sulfides 1a–h undergo smooth carbocupra-
tion with copper–zinc reagents ArCu(CN)ZnAr, prepared
by mixing Ar2Zn 2a–h with CuCN·2LiCl (1.5 equiv) at 25
°C for 3–17 hours leading to the expected alkenylcopper
compounds 3a–h (Scheme 1) with excellent diastereose-
lectivity (E/Z > 99:1) as shown by GC-analysis of the
crude hydrolyzed reaction mixture. The functionalized di-
arylzinc reagents of type 2 were prepared either by mag-
R1
Ar2Zn 2a–h
(1.5 equiv)
R1
Ar
R1
Ar
E
E+ (3 equiv)
R2S
Cu
R2S
CuCN·2LiCl
(1.5 equiv)
THF, 25 °C
3–24 h
SR2
1a–h
3a–h
E/Z > 99:1
6a–p: 57-91
E/Z > 93:7
R1,R2 = alkyl, aryl
Scheme 1 Preparation of diarylzinc reagents and their use in carbo-
cupration reactions of alkynyl sulfides
Thus, the reaction of bis(4-chlorophenyl)zinc (2a) with
the alkynyl sulfide 1a in the presence of CuCN·2LiCl8
(1.5 equiv) provided the alkenylcopper intermediate 3a at
25 °C within 16 hours. Its subsequent quenching with wa-
ter led to the alkenyl sulfide 6a in 80% yield; E/Z 97:3
(Table 1, entry 1). Similarly, the hydrolysis of the alkenyl-
copper compound 3b, obtained after carbocupration with
diphenylzinc (2b) and CuCN·2LiCl (1.5 equiv), afforded
SYNTHESIS 2011, No. 21, pp 3453–3462
x
x.
x
x
.
2
0
1
1
Advanced online publication: 07.09.2011
DOI: 10.1055/s-0030-1260210; Art ID: T74911SS
© Georg Thieme Verlag Stuttgart · New York

3454
C. Dunst et al.
PAPER
the sulfide 6b in 70% yield; E/Z 99:1 (entry 2).10 Iodolysis with allyl bromide or ethyl (2-bromomethyl)acrylate11
of the copper compounds 3a,c–e led to the alkenyl iodides furnishing the allylated alkenes 6k–m in 65–87% yield;
6c–f in 65–82% yield with excellent E/Z ratios > 99:1 (en- E/Z 93:7 (entries 11–13). Trapping the carbometalated
tries 3–6). The allylated sulfides 6g–j were obtained by alkenes 3d,h with cyclohex-2-enone in the presence of tri-
the reaction of the alkenylcopper intermediates 3e,f with methylsilyl chloride12 afforded the Michael adducts 6n,o
allyl bromide in 57–91% yield; E/Z 99:1 (entries 7–10). in 60–80% yield with an excellent E/Z ratio of 99:1 (en-
Furthermore, the alkynes 1d,g underwent smooth car- tries 14, 15). Finally, alkyne 1f was carbocuprated with
bocupration at 25 °C within eight hours with meta- or bis(3-fluorophenyl)zinc (2h) in the presence of
para-substituted organocopper reagents bearing an ester CuCN·2LiCl within eight hours at 25 °C. Its subsequent
or a methoxy group, obtained after transmetalation of the acylation with 4-chlorobenzoyl chloride gave the desired
diorganozinc reagents 2c,e,f with CuCN·2LiCl (1.5 ketone 6p in 66% yield; E/Z 93:7 (entry 16).
equiv). The resulting copper intermediates 3d,g reacted
Table 1 Carbocupration of Alkynes 1 and Reaction with Electrophiles
Entry Alkyne 1 (time)a
Zinc reagentb
Copper intermediate 3
Electrophile
H2O
Product, yield (ratio)c
Cl
Cl
Cl
SMe
Cu
H
1
NC
2
Zn
2a
1a (16 h)
SMe
SMe
NC
NC
6a: 80% (E/Z 97:3)
3a
Ph
Cu
S
Ph
H
Me2N
Ph2Zn
2
H2O
Me2N
Me2N
S
S
2b
1b (17 h)
6b: 70% (E/Z 99:1)
3b
Ph
Cu
S
Ph
I
OMe
Hex
3
2b
2b
I2
Hex
S
OMe
Hex
OMe
S
1c (15 h)
3c
6c: 80% (E/Z 99:1)
Ph
Cu
S
Ph
I
NC
4
I2
S
S
NC
NC
1d (8 h)
3d
6d: 65% (E/Z 99:1)
Cl
Cl
Cu
5
1a (16 h)
2a
I2
I
SMe
SMe
NC
NC
3a
6e: 70% (E/Z 99:1)
MeO
MeO
OMe
S
I
Cu
6
7
I2
Br
2
Zn
OMe
S
OMe
S
OMe
Br
Br
2c
1e (6 h)
6f: 82% (E/Z 99:1)
3e
Cl
Cl
Ph
SMe
2a
2c
Br
Cu
SMe
1f (8 h)
Ph
Ph
SMe
3f
6g: 57% (E/Z 99:1)
MeO
MeO
8
1f (8 h)
Br
Cu
SMe
SMe
Ph
Ph
3f
6h: 76% (E/Z 99:1)
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Synthesis of Tetrasubstituted Alkenyl Sulfides
3455
Table 1 Carbocupration of Alkynes 1 and Reaction with Electrophiles (continued)
Entry Alkyne 1 (time)a
Zinc reagentb
Copper intermediate 3
Electrophile
Product, yield (ratio)c
OMe
OMe
MeO
OMe
MeO
MeO
9
1f (8 h)
Br
Cu
SMe
2
Zn
Ph
Ph
SMe
2d
3f
6i: 70% (E/Z 99:1)
MeO
MeO
Cu
S
10
1e (6 h)
2c
Br
OMe
S
OMe
Br
Br
6j: 91% (E/Z 99:1)
3e
CO2Et
CO2Et
OMe
CO2Et
Cu
11
12
13
Br
2
S
OMe
S
OMe
NC
S
Zn
2e
1g (8 h)
NC
NC
6k: 87% (E/Z 93:7)
3g
EtO2C
EtO2C
CO2Et
CO2Et
CO2Et
Br
Cu
1d (8 h)
S
2
NC
S
Zn
NC
2f
3d
6l: 65% (E/Z 93:7)
MeO
MeO
CO2Et
Cu
CO2Et
Br
1g (8 h)
2c
S
OMe
S
OMe
NC
NC
3g
6m: 80% (E/Z 93:7)
O
O
Hex
Cu
S
14
15
2b
S
Hex
S
Hex
1h (16 h)
6n: 80% (E/Z 99:1)d
Me2N
3h
Me2N
NMe2
O
O
Cu
S
1d (8 h)
2
S
Zn
NC
NC
2g
6o: 60% (E/Z 99:1)d
3d
F
Cl
F
F
O
Cu
SMe
Cl
O
16
1f (8 h)
2
Zn
Ph
Ph
SMe
Cl
2h
3f
6p: 66% (E/Z 93:7)
a Reaction time for the carbometalation at 25 °C. First, the zinc reagent (1.5 equiv) was transmetalated using CuCN·2LiCl (1.5 equiv, –20 °C, 30 min).
b 2 MgX2·2LiCl has been omitted for the sake of clarity; X = Cl, Br.
c Isolated yield of analytically pure product. E/Z ratio determined by 2D NMR.
d TMSCl (7.5 equiv) was used.
Synthesis 2011, No. 21, 3453–3462 © Thieme Stuttgart · New York

3456
C. Dunst et al.
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Besides arylzincs, it was also possible to use bis(ben-
zyl)zinc reagents.4 Thus, bis(4-fluorobenzyl)zinc (2i,
1.5 equiv) was obtained by magnesium insertion to 4-
fluorobenzyl chloride (7) in the presence of zinc chloride
(0.55 equiv).13 The carbometalation reaction of the result-
ing diorganozinc reagent 2i with the alkynyl sulfide 1i in
the presence of CuCN·2LiCl (1.5 equiv) provided the alk-
enylcopper intermediate 3i at 25 °C in 16 hours. Its subse-
quent hydrolysis led to the benzylic sulfide 6q in 83%
yield; E/Z 99:1 (Scheme 2).
Table 2 Palladium-Catalyzed Cross-Coupling Reaction of Alkenyl
Iodides 6c,d with Zinc Reagents 8a,b at 25 °C
Entry
1
Alkenyl Zinc reagent (time) Product, yield (ratio)a
iodide
6c
Ph
Ph
Hex
S
OMe
OMe
ZnCl
8a (6 h)b
9a: 77% (E/Z 98:2)
Ph
p-Tol
S
2
6c
F
F
Hex
Mg (2.5 equiv)
LiCl (0.75 equiv)
9b: 54% (E/Z 97:3)
ZnI
ZnCl2 (0.55 equiv)
THF, 25 °C
8b (5 h)c
8a (6 h)c
Ph
Ph
3
4
6d
6d
Zn·2MgCl2·LiCl
2
Cl
7
2i
S
NC
9c: 76% (E/Z 99:1)
8b (5 h)c
Ph
p-Tol
F
Cu
S
2i (1.5 equiv)
Hex
S
CuCN·2LiCl
(1.5 equiv)
25 °C, 16 h
Hex
NC
S
9d: 82% (E/Z 99:1)
1i
3i
a Isolated yield of analytically pure product. E/Z ratio determined by
2D NMR.
H2O
b 2% Pd(OAc)2 and 4% SPhos were used.
c 3% Pd(dba)2 and 6% P(o-furyl)3 were used.
F
H
Hex
S
9b was obtained by using 3% bis(dibenzylideneacet-
one)palladium(0) [Pd(dba)2], 6% tri(2-furyl)phosphine,17
and p-tolylzinc iodide (8b) within five hours at 25 °C in
54% yield; E/Z 97:3 (entry 2). The cross-coupling reac-
tion of 6d with benzylzinc chloride (8a) or p-tolylzinc io-
dide (8b) led exclusively to the alkenes 9c,d in 76–82%
yield (E/Z 99: 1, entries 3 and 4).
6q 83%
E/Z = 99:1
Scheme 2 Preparation of the dibenzylzinc reagent 2i and carbocu-
pration of alkynyl sulfide 1i
In summary, we have reported a new copper(I)-mediated
carbometalation reaction of alkenyl sulfides with func-
tionalized aryl or benzylic diorganozinc reagents. Trap-
ping reactions with various electrophiles yielded highly
stereoselectively tetrasubstituted sulfides (E/Z 93:7 up to
99:1).
The resulting alkenyl iodides 6c–d, obtained by a car-
bocupration–iodolysis sequence, can be further used as
electrophiles in palladium-catalyzed cross-coupling reac-
tions (Scheme 3).14
All reactions were carried out under an argon atmosphere in flame-
dried glassware. Syringes which were used to transfer anhydrous
solvents or reagents were purged with argon prior to use. THF was
continuously refluxed and freshly distilled from Na benzophenone
ketyl under N2. Yields refer to isolated yields of compounds esti-
mated to be >95% pure as determined by 1H NMR (25 °C) and cap-
illary GC. Purification via column chromatography was performed
using silica gel 60 (40–63 mm 230–400 mesh ASTM); petroleum
ether = PE. All reagents were obtained from commercial sources.
Melting points were measured using a Büchi B-540 apparatus and
are uncorrected. NMR spectra were recorded in CDCl3, DMSO-d6,
acetone-d6, or C6D6. Mass spectra and HRMS were recorded using
electrospray ionization except where otherwise noted.
R3
I
Pd(0)
R3 ZnX (8a
,b)
R1
SR2
R1
SR2
25 °C, 5–6 h
6c
,
d
9a
–d: 54–82%
E/Z > 97:3
R1 = alkyl
R2 = aryl
Scheme 3 Palladium-catalyzed cross-coupling reaction of the alk-
enyl iodides 6c,d
Negishi cross-coupling15 reaction of the alkenyl iodide 6c
using 2% palladium(II) acetate, 4% 2-(dicyclohexylphos-
phino)-2¢,6¢-dimethoxybiphenyl (SPhos),16 and benzyl-
zinc chloride (8a, 1.5 equiv) afforded the alkenyl sulfide
9a in 77% yield; E/Z 98:2 (Table 2, entry 1). The sulfide
Alkynyl Sulfides 1; General Procedure 1 (GP1)
A dry and argon-flushed Schlenk-flask, equipped with a magnetic
stirring bar and septum, was charged with the alkyne dissolved in
THF (1 mL per mmol) and cooled to –78 °C. Then, n-BuLi in hex-
Synthesis 2011, No. 21, 3453–3462 © Thieme Stuttgart · New York

PAPER
Synthesis of Tetrasubstituted Alkenyl Sulfides
3457
ane (1.1 equiv) was added at –78 °C and the mixture was stirred un-
til deprotonation was complete. Then, the disulfide (1.2 equiv) was
added at this temperature, and the resulting mixture was warmed to
25 °C overnight. The mixture was quenched with sat. Na2CO3
(10 mL per mmol) and extracted with Et2O (3 × 10 mL per mmol).
The combined organic layers were dried (MgSO4), filtered, and
concentrated under reduced pressure. Purification by flash chroma-
tography (silica gel) yielded the desired alkynyl sulfide 1.
6-[(4-Methylphenyl)thio]hex-5-ynenitrile (1d)
Prepared according to GP1 from hex-5-ynenitrile (2.9 g, 30 mmol)
in THF (15 mL) (metalation conditions: –78 °C, 1.5 h). Purification
by flash chromatography (pentane) yielded 1d (3.2 g, 50%) as an
orange oil.
IR (diamond-ATR, neat): 2942 (w), 2248 (w), 1491 (m), 1425 (m),
1210 (w), 1182 (w), 1117 (w), 1084 (m), 1016 (w), 803 cm–1 (vs).
1H NMR (400 MHz, DMSO-d6): d = 7.34–7.30 (m, 2 H), 7.23–7.19
(m, 2 H), 2.60–2.56 (m, 4 H), 2.28 (s, 3 H), 1.86–1.79 (m, 2 H).
13C NMR (100 MHz, DMSO-d6): d = 136.2, 130.1, 128.5, 125.8,
120.0, 98.0, 66.0, 24.0, 20.5, 18.8, 15.6.
MS (EI, 70 eV): m/z (%) = 215 (M+, 100), 161 (41), 117 (44), 91
(14).
6-(Methylthio)hex-5-ynenitrile (1a)
Prepared according to GP1 from hexyne-5-nitrile (2.3 g, 25 mmol)
in THF (13 mL) (metalation conditions: –78 °C, 1.5 h). Purification
by flash chromatography (pentane–Et2O, 50:1) yielded 1a (1 g,
30%) as a yellow oil.
IR (diamond-ATR, neat): 2928 (m), 2247 (m), 1735 (w), 1452 (m),
1424 (vs), 1312 (s), 978 (s), 960 (m), 765 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 2.52–2.45 (m, 4 H), 2.36–2.35 (m,
3 H), 1.90–1.81 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 119.2, 89.9, 72.6, 24.6, 19.2, 19.1,
16.2.
MS (EI, 70 eV): m/z (%) = 139 (M+, 65), 124 (21), 97 (28), 85 (100),
84 (33), 45 (14).
HRMS (EI): m/z [M]+ calcd for C13H13NS: 215.0769; found:
215.0762.
1-Bromo-2-{[(4-methoxyphenyl)thio]ethynyl}benzene (1e)
To 1-bromo-2-ethynylbenzene (958 mg, 5.29 mmol) in THF (5 mL)
was added MeMgCl (1.77 mL, 5.29 mmol) at 25 °C and the mixture
was stirred for 1 h. Then, S-(4-methoxyphenyl)benzenesulfonothio-
ate (1.48 g, 5.29 mmol) in THF (5 mL) was added at –40 °C and the
resulting mixture was slowly warmed to 0 °C over 12 h. Purification
according to GP1 yielded 1e (1.48g, 86%) as a yellow oil.
HRMS (EI): m/z [M]+ calcd for C7H9NS: 139.0456; found:
139.0450.
IR (diamond-ATR, neat): 2169 (w), 1590 (m), 1491 (s), 1290 (m),
1243 (vs), 1174 (s), 1025 (s), 820 (s), 749 (s), 681 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 7.60–7.55 (m, 1 H), 7.53–7.44 (m,
3 H), 7.28–7.22 (m, 1 H), 7.18–7.11 (m, 1 H), 6.94–6.88 (m, 2 H),
3.80 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 159.1, 133.0, 132.4, 129.2, 129.0,
127.0, 125.3, 125.0, 122.5, 115.1, 95.0, 82.4, 55.4.
MS (EI, 70 eV): m/z (%) = 318 (M+, 90), 305 (23), 239 (100), 195
(34), 152 (21), 140 (19), 43 (11).
HRMS: m/z [M]+ calcd for C15H11BrOS: 317.9714; found:
317.9709.
N,N-Dimethyl-3-[(4-methylphenyl)thio]prop-2-yn-1-amine (1b)
Prepared according to GP1 from N,N-dimethylprop-2-yn-1-amine
(2.5 g, 30 mmol) in THF (15 mL) (metalation conditions: –78 °C, 1
h). Purification by flash chromatography (pentane–Et2O, 1:50 + 2
vol% Et3N) yielded 1b (4 g, 65%) as an orange oil.
IR (diamond-ATR, neat): 2972 (w), 1492 (m), 1451 (m), 1354 (m),
1322 (m), 1260 (w), 1084 (m), 1038 (s), 1016 (m), 1009 (m), 837
(m), 801 (vs), 670 cm–1 (w).
1H NMR (400 MHz, DMSO-d6): d = 7.34–7.31 (m, 2 H), 7.24–7.20
(m, 2 H), 3.49 (s, 2 H), 2.27 (s, 3 H), 2.19 (m, 6 H).
13C NMR (100 MHz, DMSO-d6): d = 136.3, 130.1, 128.4, 125.9,
[(Methylthio)ethynyl]benzene (1f)
95.3, 70.0, 48.4, 43.6, 20.5.
Prepared according to the literature procedure.18
MS (EI, 70 eV): m/z (%) = 205 (M+, 69), 204 (53), 172 (39), 162
(38), 161 (100), 147 (45), 117 (60114 (30), 91 (46).
HRMS (EI): m/z [M]+ calcd for C12H15NS: 205.0925; found:
205.0922.
4-{[(4-Methoxyphenyl)thio]ethynyl}benzonitrile (1g)
A dry and argon-flushed Schlenk-flask, equipped with a magnetic
stirring bar and a septum, was charged with 4-ethynylbenzonitrile
(1.3 g, 10 mmol) in THF (15 mL) and cooled to –78 °C. Then, i-
PrMgCl·LiCl (8.8 mL, 11 mmol) was slowly added at –78 °C and
the resulting mixture was stirred for 30 min. S-(4-Methoxyphe-
nyl)benzenesulfonothioate (3.1 g, 11 mmol) in THF (10 mL) was
added at this temperature, and the resulting mixture was allowed to
warm up to 25 °C overnight. Purification according to GP1 and
flash chromatography (pentane + 2 vol% Et3N) yielded 1g (1.72 g,
65%) as a yellow solid; mp 88–90 °C.
1-Methoxy-4-(oct-1-ynylthio)benzene (1c)
Prepared according to GP1 from oct-1-yne (2.2 g, 20 mmol) in THF
(15 mL) (metalation conditions: –78 °C, 2 h). Purification by flash
chromatography (pentane + 2 vol% Et3N) yielded 1c (3 g, 60%) as
a colorless oil.
IR (diamond-ATR, neat): 2929 (m), 1593 (w), 1492 (vs), 1462 (m),
1289 (m), 1243 (vs), 1174 (m), 1032 (s), 1006 (w), 820 (s), 623
cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 7.38–7.33 (m, 2 H), 6.91–6.86 (m,
2 H), 3.81 (s, 3 H), 2.41 (t, J = 7.1 Hz, 2 H), 1.63–1.30 (m, 8 H),
0.93–0.88 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 158.7, 128.3, 124.0, 114.9, 98.4,
66.0, 55.4, 31.3, 28.6, 28.6, 22.5, 20.3, 14.0.
MS (EI, 70 eV): m/z (%) = 248 (M+, 100), 140 (44), 139 (21), 133
(44).
IR (diamond-ATR, neat): 2844 (w), 2224 (m), 2168 (m), 1590 (m),
1570 (m), 1492 (s), 1466 (m), 1458 (m), 1442 (m), 1408 (m), 1288
(m), 1244 (s), 1172 (s), 1120 (m), 1106 (m), 1022 (s), 850 (m), 828
(vs), 808 (s), 622 cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 7.59–7.57 (m, 2 H), 7.50–7.47 (m,
2 H), 7.44–7.40 (m, 2 H), 6.94–6.90 (m, 2 H), 3.81 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 159.4, 132.0, 131.4, 129.7, 127.9,
121.7, 118.5, 115.2, 111.1, 94.5, 83.6, 55.4.
MS (EI, 70 eV): m/z (%) = 265 (M+, 100), 250 (48), 222 (14).
HRMS (EI): m/z [M]+ calcd for C16H11NOS: 265.0561; found:
HRMS (EI): m/z [M]+ calcd for C15H20OS: 248.1234; found:
243.1231.
265.0556.
Synthesis 2011, No. 21, 3453–3462 © Thieme Stuttgart · New York

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PAPER
1-Methyl-4-(oct-1-ynylthio)benzene (1h)
IR (diamond-ATR, neat): 2970 (w), 2814 (m), 2764 (m), 1491 (s),
1454 (m), 1442 (m), 1176 (m), 1092 (m), 1041 (m), 1015 (m), 852
(m), 823 (m), 803 (s), 748 (vs), 694 cm–1 (s).
1H NMR (400 MHz, DMSO-d6): d = 7.52–7.49 (m, 2 H), 7.34–7.29
(m, 4 H), 7.25–7.16 (m, 3 H), 6.74 (s, 1 H), 3.44 (s, 2 H), 2.28 (s, 3
H), 2.15 (s, 6 H).
Prepared according to GP1 from oct-1-yne (2.8 g, 25 mmol) in THF
(25 mL) (metalation conditions: –78 °C, 2 h). Purification by flash
chromatography (pentane) yielded 1h (3.2g, 55%) as a colorless oil.
IR (diamond-ATR, neat): 2955 (m), 2927 (m), 2857 (m), 1492 (m),
1465 (w), 1456 (w), 1017 (w), 801 (vs), 725 cm–1 (w).
1H NMR (400 MHz, DMSO-d6): d = 7.31–7.27 (m, 2 H), 7.21–7.17
(m, 2 H), 2.45 (t, J = 7.0 Hz, 2 H), 2.27 (s, 3 H), 1.54–1.47 (m, 2 H),
1.40–1.33 (m, 2 H), 1.29–1.22 (m, 4 H), 0.87–0.83 (m, 3 H).
13C NMR (100 MHz, DMSO-d6): d = 136.0, 130.0, 128.9, 125.5,
100.2, 64.4, 30.7, 28.0, 27.9, 22.0, 20.4, 19.5, 13.9.
13C NMR (100 MHz, DMSO-d6): d = 140.0, 137.0, 136.3, 132.0,
130.0, 129.0, 128.2, 127.0, 126.0, 125.7, 58.7, 44.7, 20.6.
MS (EI, 70 eV): m/z (%) = 283 (M+, 54), 161 (13), 160 (100), 158
(15), 58 (80).
HRMS (EI): m/z [M]+ calcd for C18H21NS: 283.1395; found:
283.1399.
MS (EI, 70 eV): m/z (%) = 232 (M+, 100), 163 (53), 161 (73), 130
(38), 124 (50), 117 (63), 91 (42), 67 (45).
1-{[(1Z)-1-Iodo-2-phenyloct-1-enyl]thio}-4-methoxybenzene
(6c); Typical Procedure (TP1)
HRMS (EI): m/z [M]+ calcd for C15H20S: 232.1286; found:
232.1266.
Prepared according to GP2 from 1c (994 mg, 4 mmol) and Ph2Zn
(2b, prepared by transmetalation of freshly titrated PhMgCl (1.43 M
in THF; 8.4 mL, 12 mmol) with ZnCl2/LiCl (6 mL, 6 mmol) at 25
°C for 10 min) (carbometalation conditions: 25 °C, 15 h). Then, the
mixture was cooled to –40 °C and 1 M I2 (5 g, 20 mmol) in THF
soln was added. The soln was stirred for 10 min at this temperature.
The reaction was quenched with sat. Na2S2O3 (150 mL) and the re-
sulting mixture was extracted with Et2O (3 × 150 mL). The com-
bined organic layers were dried (MgSO4), filtered, and concentrated
under reduced pressure. Purification by flash chromatography (pen-
tane + 2 vol% Et3N) yielded 6c (1.44 g, 80%, E/Z 99:1) as a yellow
oil.
Carbocupration of Alkynes with Functionalized Diorganozinc
Reagents; General Procedure (GP2)
A dry and argon-flushed Schlenk-flask, equipped with a magnetic
stirring bar and a septum, was charged with the diorganozinc re-
agent of type R2Zn·2MgX2·LiCl (1.5 equiv) and cooled to –20 °C.
CuCN·2LiCl (1.5 equiv) was added dropwise and the resulting mix-
ture was stirred for 30 min. Then, the alkynyl sulfide of type 1 was
added, warmed to 25 °C and stirred for the indicated time. The car-
bocupration progress was monitored by GC analysis of reaction al-
iquots, which were quenched with sat. NH4Cl soln using dodecane
as internal standard.
IR (diamond-ATR, neat): 2924 (m), 1592 (m), 1491 (s), 1452 (m),
1440 (m), 1286 (m), 1242 (s), 1179 (m), 1171 (m), 1031 (m), 825
(s), 773 (m), 746 (m), 698 (vs), 639 (m), 621 cm–1 (m).
Purification of Tetrasubstituted Alkenes; General Procedure
(P1)
The reaction mixture was quenched with sat. NH4Cl–25% NH3 in
H2O (4:1, 10 mL per mmol) and the resulting mixture was extracted
with Et2O (3 × 10 mL per mmol). The combined organic layers
were dried (MgSO4), filtered, and concentrated under reduced pres-
sure.
1H NMR (400 MHz, DMSO-d6): d = 7.40–7.36 (m, 2 H), 7.33–7.28
(m, 3 H), 7.18–7.16 (m, 2 H), 7.02–6.98 (m, 2 H), 3.77 (s, 3 H), 2.83
(d, J = 7.2 Hz, 2 H), 1.30–1.17 (m, 8 H), 0.81–0.77 (m, 3 H).
13C NMR (100 MHz, DMSO-d6): d = 159.6, 158.3, 146.0, 132.5,
128.7, 128.1, 128.0, 126.6, 115.5, 90.4, 55.7, 37.3, 31.4, 28.5, 27.9,
22.4, 14.3.
MS (EI, 70 eV): m/z (%) = 452 (M+, 16), 241 (31), 185 (100), 139
(82), 121 (19), 91 (17), 43 (12).
HRMS (EI): m/z [M]+ calcd for C21H25IOS: 452.0671; found:
452.0673.
(5E)-5-(4-Chlorophenyl)-6-(methylthio)hex-5-enenitrile (6a)
Prepared according to GP2 from 1a (209 mg, 1.5 mmol) and bis(4-
chlorophenyl)zinc (2a; 0.4 M in THF; 5.7 mL, 2.3 mmol) (carbo-
metalation conditions: 25 °C, 16 h). Purification according to P1
and flash chromatography (pentane–Et2O, 9:1 + 2 vol% Et3N)
yielded 6a (201 mg, 80%, E/Z 97:3) as a yellow oil.
IR (diamond-ATR, neat): 2924 (w), 1491 (m), 1424 (m), 1398 (w),
1091 (m), 1010 (m), 803 (vs), 646 cm–1 (w).
(5Z)-6-Iodo-6-[(4-methylphenyl)thio]-5-phenylhex-5-enenitrile
(6d)
1H NMR (400 MHz, CDCl3): d = 7.30–7.26 (m, 2 H), 7.24–7.20 (m,
2 H), 6.28 (s, 1 H), 2.72–2.69 (m, 2 H), 2.38 (s, 3 H), 2.31 (t, J = 7.2
Hz, 2 H), 1.81–1.73 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 138.7, 134.5, 132.9, 128.8, 128.4,
126.8, 119.4, 30.3, 23.6, 17.4, 16.7.
MS (EI, 70 eV): m/z (%) = 251 (M+, 100), 199 (20), 197 (51), 195
(30), 163 (16), 149 (24), 115 (11).
HRMS (EI): m/z [M]+ calcd for C13H14ClNS: 251.0535; found:
251.0534.
Prepared according to TP1 from 1d (431 mg, 2 mmol) and Ph2Zn
(2b, prepared by transmetalation of freshly titrated PhMgCl (1.43 M
in THF; 4.2 mL, 6 mmol) with ZnCl2/LiCl (3 mL, 3 mmol) at 25 °C
for 10 min) (carbometalation conditions: 25 °C, 8 h). Purification by
flash chromatography (pentane–Et2O, 1:1 + 2 vol% Et3N) yielded
6d (273 mg, 65%, E/Z 99:1) as a white solid; mp 75–77 °C.
IR (diamond-ATR, neat): 2927 (w), 1489 (m), 1453 (w), 1074 (w),
831 (m), 802 (s), 762 (m), 752 (m), 729 (w), 700 (vs), 675 cm–1 (w).
1H NMR (400 MHz, DMSO-d6): d = 7.43–7.32 (m, 3 H), 7.29–7.24
(m, 6 H), 2.94–2.46 (m, 2 H), 2.52–2.46 (m, 2 H), 2.30 (s, 3 H),
1.59–1.51 (m, 2 H).
13C NMR (100 MHz, DMSO-d6): d = 157.4, 144.9, 136.9, 131.9,
130.0, 129.5, 128.3, 127.8, 127.7, 120.1, 89.2, 35.7, 23.5, 20.7,
15.7.
MS (EI, 70 eV): m/z (%) = 419 (M+, 12), 293 (20), 292 (100), 275
(27), 225 (27), 224 (67), 103 (10).
HRMS (EI): m/z [M]+ calcd for C19H18INS: 419.0205; found:
419.0198.
Dimethyl{(2Z)-3-[(4-methylphenyl)thio]-2-phenylprop-2-
enyl}amine (6b)
Prepared according to GP2 from 1b (205 mg, 1.0 mmol) and Ph2Zn
(2b, prepared by transmetalation of freshly titrated PhMgCl (1.43 M
in THF; 4.2 mL, 6 mmol) with ZnCl2/LiCl (3 mL, 3 mmol) at 25 °C
for 10 min) (carbometalation conditions: 25 °C, 17 h). Purification
according to P1 and flash chromatographical purification (pentane–
Et2O, 5:1 + 2 vol% Et3N) yielded 6b (198 mg, 70%, E/Z 99:1) as a
colorless oil.
Synthesis 2011, No. 21, 3453–3462 © Thieme Stuttgart · New York

PAPER
Synthesis of Tetrasubstituted Alkenyl Sulfides
3459
(5Z)-5-(4-Chlorophenyl)-6-iodo-6-(methylthio)hex-5-enenitrile
(6e)
MS (EI, 70 eV): m/z (%) = 300 (M+, 100), 253 (20), 252 (20), 246
(18), 244 (59), 218 (20), 217 (26), 125 (16), 91 (14).
Prepared according to TP1 from 1a (209 mg, 1.5 mmol) and bis(4-
chlorophenyl)zinc (2a; 0.4 M in THF; 5.7 mL, 2.3 mmol) (carbo-
metalation conditions: 25 °C, 16 h). Purification by flash chroma-
tography (pentane–Et2O, 5:1 + 2 vol% Et3N) yielded 6e (264 mg,
70%, E/Z 99:1) as a yellow oil.
HRMS (EI): m/z [M]+ calcd for C18H17ClS: 300.0739; found:
300.0740.
1-Methoxy-4-[(1Z)-2-(methylthio)-1-phenylpenta-1,4-di-
enyl]benzene (6h)
IR (diamond-ATR, neat): 2918 (w), 1482 (s), 1452 (m), 1421 (m),
1395 (m), 1167 (w), 1088 (s), 1013 (s), 969 (m), 835 (vs), 809 (s),
784 (m), 719 (m), 649 (m), 618 cm–1 (m).
1H NMR (400 MHz, CDCl3): d = 7.35 (d, J = 8.2 Hz, 2 H), 7.05 (d,
J = 8.2 Hz, 2 H), 2.92–2.88 (m, 2 H), 2.35 (s, 3 H), 2.31 (t, J = 7.2
Hz, 2 H), 1.72–1.64 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 151.2, 143.8, 133.8, 129.4, 128.8,
119.0, 96.9, 36.1, 23.7, 22.7, 16.6.
MS (EI, 70 eV): m/z (%) = 377 (M+, 12), 252 (39), 251 (19), 250
(100), 175 (26), 167 (21), 137 (12).
Prepared according to TP2 from 1f (373 mg, 2 mmol) and bis(4-
methoxyphenyl)zinc (2c; 0.37 M in THF; 8.11 mL, 3 mmol) (carbo-
metalation conditions: 25 °C, 8 h). Purification by flash chromato-
graphy (pentane + 2 vol% Et3N) yielded 6h (451 mg, 76%, E/Z
99:1) as a yellow oil.
IR (diamond-ATR, neat): 2969 (w), 1739 (s), 1604 (m), 1506 (vs),
1440 (m), 1365 (m), 1281 (m), 1242 (vs), 1217 (s), 1172 (m), 1031
(m), 832 (s), 799 (m), 774 (m), 740 (m), 697 cm–1 (vs).
1H NMR (300 MHz, C6D6): d = 7.45–7.41 (m, 2 H), 7.21–7.12 (m,
4 H), 7.08–7.02 (m, 1 H), 6.72–6.67 (m, 2 H), 6.05–5.92 (m, 1 H),
5.27–5.20 (m, 1 H), 5.13–5.08 (m, 1 H), 3.27 (s 3 H), 3.17–3.14 (m,
2 H), 1.84 (s, 3 H).
13C NMR (75 MHz, C6D6): d = 159.0, 143.4, 140.7, 136.7, 135.4,
133.2, 130.7, 130.3, 128.3, 127.0, 116.0, 113.9, 54.7, 37.3, 15.2.
MS (EI, 70 eV): m/z (%) = 297 (17), 296 (M+, 100), 249 (13), 248
HRMS (EI): m/z [M]+ calcd for C13H13ClINS: 376.9502; found:
376.9490.
1-Bromo-2-{(E)-2-iodo-1-(4-methoxyphenyl)-2-[(4-methoxy-
phenyl)thio]vinyl}benzene (6f)
Prepared according to TP1 from 1e (638 mg, 2 mmol) and bis(4-
methoxyphenyl)zinc (2c; 0.37 M in THF; 8.11 mL, 3 mmol) (carbo-
metalation conditions: 25 °C, 6 h). Purification by flash chromato-
graphy (pentane–Et2O, 3:1 + 2 vol% Et3N) yielded 6f (908 mg,
82%, E/Z 99:1) as a yellow oil.
(10), 240 (53), 225 (13).
HRMS (EI): m/z [M]+ calcd for C19H20OS: 296.1235; found:
296.1227.
1,3-Dimethoxy-5-[(1E)-2-(methylthio)-1-phenylpenta-1,4-di-
enyl]benzene (6i)
Prepared according to TP2 from 1f (373 mg, 2 mmol) and bis(3,5-
dimethoxyphenyl)zinc (2d; 0.54 M in THF; 5.5 mL, 3 mmol) (car-
bometalation conditions: 25 °C, 7 h). Purification by flash chroma-
tography (pentane + 2 vol% Et3N) yielded 6i (457 mg, 70%, E/Z
99:1) as a yellow oil.
IR (diamond-ATR, neat): 2956 (w), 1590 (m), 1504 (m), 1492 (s),
1462 (m), 1440 (m), 1288 (m), 1244 (vs), 1172 (s), 1028 (s), 826 (s),
770 (m), 742 (s), 708 (w), 640 cm–1 (w).
1H NMR (400 MHz, acetone-d6): d = 7.63 (dd, J = 8.1 Hz, 1.1 Hz,
1 H), 7.51 (dd, J = 7.6, 1.8 Hz, 1 H), 7.45–7.37 (m, 5 H), 7.27–7.21
(m, 1 H), 6.99–6.93 (m, 2 H), 6.91–6.86 (m, 2 H), 3.82 (s, 3 H), 3.78
(s, 3 H).
13C NMR (100 MHz, acetone-d6): d = 161.1, 160.3, 152.4, 143.2,
136.7, 135.1, 133.7, 131.4, 131.0, 130.1, 128.6, 127.6, 122.9, 115.5,
114.0, 97.7, 55.7, 55.5.
MS (EI, 70 eV): m/z (%) = 552 (M+, 14), 473 (24), 427 (69), 346
(100), 331 (24), 139 (24).
HRMS (EI): m/z [M]+ calcd for C22H18BrIO2S: 551.9256; found:
551.9249.
IR (diamond-ATR, neat): 1581 (s), 1449 (m), 1418 (m), 1342 (m),
1264 (m), 1201 (s), 1148 (vs), 1064 (m), 1047 (m), 908 (m), 849
(m), 836 (s), 813 (m), 706 (vs), 694 (s), 664 cm–1 (m).
1H NMR (400 MHz, C6D6): d = 7.48–7.46 (m, 2 H), 7.14–7.12 (m,
2 H), 7.03–6.99 (m, 1 H), 6.58 (d, J = 2.3 Hz, 2 H), 6.45 (t, J = 2.2
Hz, 1 H), 5.99–5.89 (m, 1 H), 5.23–5.18 (m, 1 H), 5.07–5.03 (m, 1
H), 3.24 (s, 6 H), 3.16–3.14 (m, 2 H), 1.79 (s, 3 H).
13C NMR (100 MHz, C6D6): d = 161.3, 145.0, 142.6, 140.6, 136.7,
134.0, 130.0, 128.4, 127.1, 116.0, 107.7, 99.6, 54.8, 37.3, 15.0.
1-Chloro-4-[(1Z)-2-(methylthio)-1-phenylpenta-1,4-dienyl]ben-
zene (6g); Typical Procedure (TP2)
MS (EI, 70 eV): m/z (%) = 326 (M+, 100), 311 (25), 279 (44), 278
(86), 270 (42), 264 (25), 203 (14), 139 (13), 91 (11).
Prepared according to GP2 from 1f (373 mg, 2 mmol) and bis(4-
chlorophenyl)zinc (2a; 0.55 M in THF; 5.4 mL, 3 mmol) (carbomet-
alation conditions: 25 °C, 3 h). Then, the mixture was cooled to
–40 °C and allyl bromide (0.58 mL, 6 mmol) was added. The soln
was stirred for 30 min at this temperature followed by 30 min at 0
°C. Purification according to P1 and flash chromatographical puri-
fication (pentane + 2 vol% Et3N) yielded 6g (343 mg, 57%, E/Z
99:1) as a white solid; mp 55–56 °C.
HRMS (EI): m/z [M]+ calcd for C20H22O2S: 326.1341; found:
326.1338.
1-Bromo-2-{(1Z)-1-(4-methoxyphenyl)-2-[(4-methoxyphe-
nyl)thio]penta-1,4-dienyl}benzene (6j)
Prepared according to TP2 from 1e (318 mg, 1 mmol) and bis(4-
methoxyphenyl)zinc (2c; 0.37 M in THF; 4.05 mL, 1.5 mmol) (car-
bometalation conditions: 25 °C, 6 h). Purification by flash chroma-
tography (pentane–Et2O, 12:1 + 2 vol% Et3N) yielded 6j (426 mg,
91%, E/Z 99:1) as a yellow oil.
IR (diamond-ATR, neat): 2982 (w), 1485 (s), 1440 (m), 1426 (m),
1391 (m), (m), 1087 (s), 1070 (m), 1013 (s), 989 (m), 915 (vs), 836
(vs), 825 (m), 779 (s), 759 (vs), 721 (s), 701 (vs), 618 (m), 608
cm–1 (m).
1H NMR (400 MHz, C6D6): d = 7.32–7.29 (m, 2 H), 7.18–7.13 (m,
2 H), 7.06–7.00 (m, 3 H), 6.94–6.91 (m, 2 H), 5.90–5.80 (m, 1 H),
5.18–5.12 (m, 1 H), 5.08–5.04 (m, 1 H), 2.97–2.95 (m, 2 H), 1.78
(s, 3 H).
IR (diamond-ATR, neat): 1592 (m), 1508 (m), 1492 (s), 1462 (m),
1440 (m), 1284 (m), 1242 (vs), 1172 (s), 1104 (m), 1028 (s), 914
(m), 828 (s), 800 (m), 766 (m), 742 (s), 626 cm–1 (w).
1H NMR (400 MHz, acetone-d6): d = 7.63–7.59 (m, 1 H), 7.47–7.43
(m, 1 H), 7.42–7.36 (m, 3 H), 7.34–7.28 (m, 2 H), 7.22–7.16 (m, 1
H), 6.93–6.84 (m, 4 H), 5.89–5.78 (m, 1 H), 5.06–4.97 (m, 2 H),
3.79 (s, 3 H), 3.76 (s, 3 H), 3.01–2.96 (m, 2 H).
13C NMR (100 MHz, C6D6): d = 142.5, 141.3, 139.0, 136.2, 134.7,
133.0, 130.9, 130.2, 128.6, 128.4, 127.2, 116.2, 36.9, 15.0.
Synthesis 2011, No. 21, 3453–3462 © Thieme Stuttgart · New York

3460
C. Dunst et al.
PAPER
Ethyl (4E)-5-(4-Cyanophenyl)-5-(4-methoxyphenyl)-4-[(4-
methoxyphenyl)thio]-2-methylenepent-4-enoate (6m)
Prepared according to TP3 from 1g (265 mg, 1 mmol) and bis(4-
methoxyphenyl)zinc (2c; 0.37 M in THF; 4 mL, 1.5 mmol) (carbo-
metalation conditions: 25 °C, 8 h). Purification by flash chromato-
graphy (pentane–Et2O, 1:1 + 2 vol% Et3N) yielded 6m (388 mg,
80%, E/Z 93:7) as a yellow oil.
13C NMR (100 MHz, acetone-d6): d = 160.7, 159.8, 144.7, 141.6,
136.5, 136.0, 135.7, 133.6, 133.0, 132.1, 131.1, 129.5, 128.4, 124.6,
124.1, 116.6, 115.4, 114.2, 55.6, 55.5, 36.1.
MS (EI, 70 eV): m/z (%) = 466 (M+, 6), 387 (100), 346 (39), 279 (1),
215 (2), 139 (2).
HRMS (EI): m/z [M]+ calcd for C25H23BrO2S: 466.0602; found:
466.0600.
IR (diamond-ATR, neat): 2836 (w), 1712 (s), 1604 (m), 1592 (m),
1508 (m), 1492 (s), 1462 (m), 1284 (m), 1242 (vs), 1172 (s), 1136
(s), 1106 (m), 1028 (s), 828 (s), 808 (m), 618 cm–1 (w).
1H NMR (400 MHz, DMSO-d6): d = 7.81–7.78 (m, 2 H), 7.49–7.48
(m, 2 H), 7.26–7.11 (m, 2 H), 6.91–6.87 (m, 4 H), 6.20 (d, J = 0.9
Hz, 1 H), 5.71 (d, J = 0.9 Hz, 1 H), 3.98 (q, J = 7.2 Hz, 2 H), 3.73
(s, 3 H), 3.71 (s, 3 H), 3.09 (s, 2 H), 1.09 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, DMSO-d6): d = 165.5, 159.2, 158.5, 147.0,
142.2, 136.6, 134.4, 132.6, 132.6, 132.1, 130.1, 129.6, 126.3, 122.6,
118.7, 114.7, 113.9, 109.6, 60.3, 55.2, 55.0, 33.6, 13.9.
MS (EI, 70 eV): m/z (%) = 485 (M+, 100), 346 (63), 345 (50), 317
(32), 316 (75), 272 (23), 140 (28).
HRMS (EI): m/z [M]+ calcd for C29H27NO4S: 485.1661; found:
485.1651.
Ethyl 3-{(1Z)-1-(4-Cyanophenyl)-2-[(4-methoxyphe-
nyl)thio]penta-1,4-dienyl}benzoate (6k)
Prepared according to TP2 from 1g (265 mg, 1 mmol) and
bis[3-(ethoxycarbonyl)phenyl]zinc (2e, prepared by adding
i-PrMgCl·LiCl (3 mmol) to 1.0 M ethyl 3-iodobenzoate (828 mg,
3 mmol) in THF at –20 °C and stirring for 0.5 h and further trans-
metalation with ZnCl2 (1.5 mL, 1.5 mmol) at –20 °C for 10 min)
(carbometalation conditions: 25 °C, 8 h). Purification by flash chro-
matography (pentane–Et2O, 19:1 + 2 vol% Et3N) yielded 6k
(395 mg, 87%, E/Z 93:7) as a yellow oil.
IR (diamond-ATR, neat): 1714 (s), 1592 (m), 1492 (s), 1462 (m),
1284 (s), 1244 (vs), 1222 (m), 1172 (s), 1104 (m), 1082 (m), 1026
(m), 914 (m), 826 (s), 764 (m), 740 (m), 708 (m), 628 cm–1 (w).
1H NMR (400 MHz, DMSO-d6): d = 7.88–7.85 (m, 1 H), 7.82–7.78
(m, 3 H), 7.53–7.48 (m, 4 H), 7.37–7.33 (m, 2 H), 6.95–6.91 (m, 2
H), 5.80–5.70 (m, 1 H), 5.05–5.02 (m, 1 H), 4.92–4.87 (m, 1 H),
4.28 (q, J = 7.1 Hz, 2 H), 3.74 (s, 3 H), 2.80 (d, J = 6.2 Hz, 2 H),
1.28 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, DMSO-d6): d = 165.3, 159.3, 146.5, 140.9,
140.0, 135.7, 134.7, 134.4, 133.5, 132.2, 130.3, 130.1, 129.2, 129.0,
128.2, 122.5, 118.7, 116.7, 114.9, 109.8, 60.8, 55.2, 35.9, 14.1.
MS (EI, 70 eV): m/z (%) = 456 (36), 455 (M+, 100), 140 (21), 139
(10).
3-{(1E)-1-[(4-Methylphenyl)thio]-2-phenyloct-1-enyl}cyclohex-
anone (6n); Typical Procedure (TP4)
Prepared according to GP2 from 1h (465 mg, 2 mmol) and Ph2Zn
[2b, prepared by transmetalation of freshly titrated PhMgCl (1.43 M
in THF; 4.2 mL, 6 mmol) with ZnCl2/LiCl (3 mL, 3 mmol) at 25 °C
for 10 min] (carbometalation conditions: 25 °C, 10 h). Then, the
mixture was cooled to –40 °C and a premixed soln of TMSCl (2.24
mL, 17.5 mmol) and cyclohex-2-enone (0.68 mL, 7 mmol) was
added. The soln was stirred for at this temperature and slowly
warmed to 0 °C overnight. Purification according to P1 and flash
chromatographical purification (pentane–Et2O, 5:1 + 2 vol% Et3N)
yielded 6n (651 mg, 80%, E/Z 99:1) as a colorless oil.
HRMS (EI): m/z [M]+ calcd for C28H27NO4S: 455.1555; found:
455.1563.
IR (diamond-ATR, neat): 2953 (m), 2926 (m), 2856 (m), 1712 (vs),
1490 (s), 1446 (m), 1258 (m), 1222 (m), 1117 (m), 1080 (m), 803
(s), 777 (m), 702 cm–1 (vs).
1H NMR (400 MHz, DMSO-d6): d = 7.43–7.39 (m, 2 H), 7.34–7.27
(m, 1 H), 7.21–7.18 (m, 4 H), 7.15–7.13 (m, 2 H), 2.73–2.65 (m, 1
H), 2.61–2.51 (m, 3 H), 2.25 (s, 3 H), 2.22–2.17 (m, 1 H), 1.99–1.91
(m, 2 H), 1.85–1.79 (m, 1 H), 1.73–1.66 (m, 1 H), 1.55–1.52 (m, 1
H), 1.24–1.15 (m, 1 H), 1.10–1.00 (m, 8 H), 0.74–0.71 (m, 3 H).
13C NMR (100 MHz, DMSO-d6): d = 209.7, 153.0, 144.8, 140.9,
134.4, 133.9, 130.7, 129.8, 128.5, 127.3, 127.3, 126.0, 45.8, 44.1,
37.0, 30.9, 29.5, 28.4, 26.7, 24.3, 21.8, 20.4, 13.8.
MS (EI, 70 eV): m/z (%) = 407 (27), 406 (M+, 100), 335 (19), 283
(14), 91 (12).
Ethyl 4-{(1E)-1-(3-Cyanopropyl)-4-(ethoxycarbonyl)-2-[(4-
methylphenyl)thio]penta-1,4-dienyl)}benzoate (6l); Typical
Procedure (TP3)
Prepared according to GP2 from 1d (215 mg, 1 mmol) and
bis[4-(ethoxycarbonyl)phenyl]zinc (2f, prepared by adding
i-PrMgCl·LiCl (1.96 mL, 2.95 mmol) to 1 M ethyl 4-iodobenzoate
(828 mg, 3 mmol) in THF at –20 °C and stirring for 0.5 h and further
transmetalation with ZnCl2 (1.5 mL, 1.5 mmol) at –20 °C for 10
min) (carbometalation conditions: 25 °C, 8 h), Then, the mixture
was cooled to –40 °C and ethyl 2-(bromomethyl)acrylate11 (580 mg,
3 mmol) was added. Purification according to P1 and flash chro-
matographical purification (pentane–Et2O, 1:1 + 2 vol% Et3N)
yielded 6l (273 mg, 65%, E/Z 93:7) as a yellow oil.
IR (diamond-ATR, neat): 1711 (vs), 1403 (m), 1367 (m), 1271 (vs),
1221 (m), 1176 (m), 1138 (s), 1102 (s), 1018 (s), 947 (m), 862 (m),
808 (s), 780 (m), 712 cm–1 (m).
HRMS (EI): m/z [M]+ calcd for C27H34OS: 406.2330; found:
406.2321.
1H NMR (400 MHz, DMSO-d6): d = 7.96–7.93 (m, 2 H), 7.41–7.38
(m, 2 H), 7.23–7.15 (m, 4 H), 6.09 (d, J = 0.9 Hz, 1 H), 5.51 (d, J =
1.2 Hz, 1 H), 4.30 (q, J = 7.1 Hz, 2 H), 3.94 (q, J = 7.0 Hz, 2 H),
2.89–2.85 (m, 4 H), 2.48–2.45 (m, 2 H), 2.28 (s, 3 H), 1.57–1.50 (m,
2 H), 1.30 (t, J = 7.0 Hz, 3 H), 1.09 (t, J = 7.0 Hz, 3 H).
13C NMR (100 MHz, DMSO-d6): d = 165.6, 165.3, 145.6, 145.5,
136.8, 136.6, 130.5, 129.9, 129.8, 129.2, 128.9, 128.9, 128.1, 126.1,
120.2, 60.7, 60.3, 35.0, 34.4, 23.5, 20.6, 15.9, 14.1, 13.8.
MS (EI, 70 eV): m/z (%) = 477 (M+, 20), 365 (25), 354 (51), 308
(100), 284 (35), 280 (55), 279 (33), 238 (72), 129 (15), 124 (19), 86
(18).
HRMS (EI): m/z [M]+ calcd for C28H31NO4S: 477.1974; found:
477.1970.
(5E)-5-[4-(Dimethylamino)phenyl]-6-[(4-methylphenyl)thio]-6-
(3-oxocyclohexyl)hex-5-enenitrile (6o)
Prepared according to TP4 from 1d (217 mg, 1 mmol) and bis[4-
(dimethylamino)phenyl]zinc (2g; 0.42 M in THF; 3.6 mL, 1.5
mmol) (carbometalation conditions: 25 °C, 8 h). Purification by
flash chromatography (pentane–Et2O, 1:1 + 2 vol% Et3N) yielded
6o (260 mg, 60%, E/Z 99:1) as a yellow oil.
IR (diamond-ATR, neat): 2932 (m), 2860 (m), 1708 (vs), 1608 (vs),
1518 (vs), 1490 (s), 1446 (m), 1350 (s), 1258 (m), 1222 (s), 1196
(m), 1116 (m), 1062 (m), 946 (m), 820 (s), 804 (vs), 736 cm–1 (m).
1H NMR (400 MHz, DMSO-d6): d = 7.18–7.13 (m, 4 H), 7.07–7.04
(m, 2 H), 6.76–6.72 (m, 2 H), 2.91 (s, 6 H), 2.72–2.62 (m, 2 H),
2.57–2.51 (m, 1 H), 2.29 (t, J = 7.1 Hz, 2 H), 2.26 (s, 3 H), 2.23–
Synthesis 2011, No. 21, 3453–3462 © Thieme Stuttgart · New York

PAPER
Synthesis of Tetrasubstituted Alkenyl Sulfides
3461
2.18 (m, 1 H), 2.02–1.92 (m, 2 H), 1.88–1.82 (m, 1 H), 1.77–1.67
(m, 1 H), 1.58–1.54 (m, 1 H), 1.35–1.22 (m, 4 H).
1-{[(1E)-1-Benzyl-2-phenyloct-1-enyl]thio}-4-methoxybenzene
(9a)
In a dry and argon-flushed Schlenk flask equipped with a septum
and a magnetic stirring bar, 6c (452 mg, 1 mmol) was dissolved in
THF (1 mL). Then, Pd(OAc)2 (4.5 mg, 2 mol%), SPhos16 (16.4 mg,
4 mol%), and BnZnCl (8a; 1.19 M in THF; 1.36 mL, 1.5 mmol)
were added at 0 °C and the mixture was warmed to 25 °C and stirred
at this temperature for 6 h. The mixture was quenched with sat.
NH4Cl soln (10 mL) and the resulting mixture was extracted with
Et2O (3 × 10 mL). The combined organic layers were dried
(MgSO4), filtered, and concentrated under reduced pressure. Purifi-
cation by flash chromatography (pentane + 2 vol% Et3N) yielded 9a
(112 mg, 77%, E/Z 98:2) as a colorless oil.
13C NMR (100 MHz, DMSO-d6): d = 209.9, 151.9, 149.5, 134.4,
134.0, 130.9, 129.9, 128.2, 127.1, 125.9, 120.3, 112.0, 45.9, 45.7,
44.1, 36.1, 29.5, 24.3, 23.3, 20.5, 15.8, 11.6.
MS (EI, 70 eV): m/z (%) = 433 (29), 432 (M+, 100), 309 (17), 251
(10).
HRMS (EI): m/z [M]+ calcd for C27H32N2OS: 432., 2235; found:
432.2232.
(2Z)-1-(4-Chlorophenyl)-3-(3-fluorophenyl)-2-(methylthio)-3-
phenylprop-2-en-1-one (6p)
Prepared according to GP2 from 1f (373 mg, 2 mmol) and bis(3-
fluorophenyl)zinc (2h; 0.41 M in THF; 7.3 mL, 3 mmol) (carbomet-
alation conditions: 25 °C, 8 h). Then, the mixture was cooled to –78
°C and 4-chlorobenzoyl chloride (0.77 mL, 6 mmol) was added.
The soln was slowly warmed to –20 °C overnight. Purification ac-
cording to P1 and flash chromatographical purification (pentane–
Et2O, 98:2 + 2 vol% Et3N) yielded 6p (505 mg, 66%, E/Z 93:7) as
a white solid; mp 79–82 °C.
IR (diamond-ATR, neat): 2925 (m), 1592 (m), 1492 (s), 1462 (m),
1452 (m), 1440 (m), 1286 (m), 1243 (vs), 1179 (m), 1171 (m), 1031
(m), 825 (s), 747 (m), 698 cm–1 (vs).
1H NMR (400 MHz, DMSO-d6): d = 7.37–7.32 (m, 3 H), 7.29–7.25
(m, 2 H), 7.23–7.11 (m, 7 H), 6.91–6.88 (m, 2 H), 3.73 (s, 3 H), 3.26
(s, 2 H), 2.80–2.76 (m, 2 H), 1.28–1.17 (m, 8 H), 0.81–0.78 (m, 3
H).
13C NMR (100 MHz, DMSO-d6): d = 159.0, 147.5, 141.9, 139.6,
132.8, 129.7, 128.8, 128.6, 128.5, 128.3, 127.5, 126.3, 124.9, 115.3,
55.6, 46.1, 36.6, 31.4, 28.8, 27.8, 22.4, 14.3.
IR (diamond-ATR, neat): 1660 (s), 1581 (s), 1569 (m), 1479 (m),
1426 (m), 1398 (m), 1233 (m), 1214 (s), 1167 (m), 1093 (s), 1084
(m), 1010 (m), 914 (m), 837 (m), 789 (s), 752 (m), 722 (s), 696 (vs),
680 (m), 628 (s), 610 cm–1 (m).
MS (EI, 70 eV): m/z (%) = 416 (M+, 75), 206 (15), 205 (25), 140
(22), 139 (46), 129 (14), 115 (17), 91 (100), 43 (15).
HRMS (EI): m/z [M]+ calcd for C28H32OS: 416.2174; found:
416.2167.
1H NMR (300 MHz, C6D6): d = 7.83–7.79 (m, 2 H), 7.37–7.34 (m,
2 H), 7.20–7.18 (m, 2 H), 7.12–7.08 (m, 1 H), 7.02–6.98 (m, 1 H),
6.94–6.87 (m, 3 H), 6.61–6.55 (m, 1 H), 6.45–6.40 (m, 1 H), 1.80
(s, 3 H).
1-Methoxy-4-{[(1E)-1-(4-methylphenyl)-2-phenyloct-1-
enyl]thio}benzene (9b); Typical Procedure (TP5)
13C NMR (75 MHz, C6D6): d = 191.7, 162.6 (d, J = 246.9 Hz), 142.9
(d, J = 7.5 Hz), 140.4 (d, J = 2.1 Hz), 140.0, 139.9, 134.8, 134.4,
130.9, 130.2, 129.8 (d, J = 8.3 Hz), 129.1, 128.6, 128.4, 125.9 (d,
J = 2.8 Hz), 117.0 (d, J = 21.9 Hz), 114.9 (d, J = 21.1 Hz), 15.9.
MS (EI, 70 eV): m/z (%) = 382 (M+, 100), 243 (57), 228 (69), 197
(24), 196 (28), 139 (62), 111 (23).
In a dry and argon-flushed Schlenk flask equipped with a septum
and a magnetic stirring bar, 6c (181 mg, 0.4 mmol) was dissolved in
THF (0.5 mL). Then, Pd(dba)2 (6.9 mg, 3 mol%), P(o-furyl)317 (5.6
mg, 6 mol%), and p-tolylzinc iodide (8b; 0.67 M in THF; 0.9 mL,
0.6 mmol) were added at 0 °C and the mixture was warmed to 25 °C
and stirred at this temperature for 5 h. The mixture was quenched
with sat. NH4Cl soln (10 mL) and the resulting mixture was extract-
ed with Et2O (3 × 10 mL). The combined organic layers were dried
(MgSO4), filtered, and concentrated under reduced pressure. Purifi-
cation by flash chromatography (pentane + 2 vol% Et3N) yielded 9b
(90 mg, 54%, E/Z 97:3) as a colorless oil.
HRMS (EI): m/z [M]+ calcd for C22H16ClFOS: 382.0594; found:
382.0590.
1-Fluoro-4-{2-hexyl-3-[(4-methylphenyl)thio]prop-2-enyl}ben-
zene (6q)
Prepared according to GP2 from 1i (232 mg, 1 mmol) and bis(4-
fluorobenzyl)zinc (2i; 0.38 M in THF; 3.9 mL, 1.5 mmol) (carbo-
metalation conditions: 25 °C, 16 h). Purification according to P1
and flash chromatographical purification (pentane–Et2O, 9:1 + 2
vol% Et3N) yielded 6q (284 mg, 83%, E/Z 99:1) as a colorless oil.
IR (diamond-ATR, neat): 2923 (m), 1593 (m), 1491 (s), 1462 (m),
1441 (m), 1285 (m), 1243 (vs), 1179 (m), 1172 (m), 1032 (s), 821
(s), 804 (s), 766 (m), 698 (s), 640 cm–1 (m).
1H NMR (400 MHz, DMSO-d6): d = 7.14–7.01 (m, 7 H), 6.90–6.87
(m, 2 H), 6.75–6.71 (m, 4 H), 3.63 (s, 3 H), 2.96 (t, J = 7.0 Hz, 2 H),
2.05 (s, 3 H), 1.29–1.19 (m, 8 H), 0.83–0.79 (m, 3 H).
13C NMR (100 MHz, DMSO-d6): d = 163.3, 163.3, 151.8, 147.2,
141.6, 140.5, 137.0, 135.6, 134.2, 133.0, 133.0, 131.5, 130.0, 119.6,
60.2, 44.7, 42.7, 36.2, 33.6, 33.0, 27.2, 25.7, 19.1.
MS (EI, 70 eV): m/z (%) = 417 (31), 416 (M+, 100), 237 (16), 131
(18), 117 (20), 105 (31), 91 (18).
HRMS (EI): m/z [M]+ calcd for C28H32OS: 416.2174; found:
416.2162.
IR (diamond-ATR, neat): 2954 (w), 2926 (m), 2856 (w), 1508 (vs),
1492 (m), 1466 (w), 1220 (vs), 1156 (m), 1092 (m), 1016 (w), 820
(s), 804 (s), 734 cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 7.20–7.08 (m, 6 H), 7.00–6.94 (m,
2 H), 5.89 (s, 1 H), 3.41 (s, 2 H), 2.31 (s, 3 H), 2.20–2.16 (m, 2 H),
1.42–1.23 (m, 8 H), 0.89–0.85 (m, 3 H).
13C NMR (100 MHz, CDCl3): d = 161.5 (d, J = 244.2 Hz), 143.9 (d,
J = 0.8 Hz), 135.9, 134.8 (d, J = 3.1 Hz), 133.3, 130.4 (d, J = 8.1
Hz), 129.7, 128.7, 119.5, 115.2 (d, J = 21.5 Hz), 42.4, 31.7, 31.6,
29.2, 27.7, 22.6, 20.9, 14.1.
MS (EI, 70 eV): m/z (%) = 343 (23), 342 (M+, 100), 147 (17), 135
(13), 109 (31).
HRMS (EI): m/z [M]+ calcd for C22H27FS: 342.1817; found:
342.1809.
(5E)-6-[(4-Methylphenyl)thio]-5,7-diphenylhept-5-enenitrile
(9c)
Prepared according to TP5 from 6d (105 mg, 0.25 mmol) and
BnZnCl (8a; 1.19 M in THF; 0.32 mL, 0.38 mmol) (reaction condi-
tions: 25 °C, 6 h). Purification by flash chromatography (pentane–
Et2O, 5:1 + 2 vol% Et3N) yielded 9c (73 mg, 76%, E/Z 99:1) as a
colorless oil.
Synthesis 2011, No. 21, 3453–3462 © Thieme Stuttgart · New York

3462
C. Dunst et al.
PAPER
(3) (a) Ogilvie, W. W.; Flynn, A. B. Chem. Rev. 2007, 107,
IR (diamond-ATR, neat): 3025 (w), 2921 (w), 1491 (m), 1452 (m),
1262 (w), 1210 (w), 1180 (w), 1083 (w), 806 (s), 774 (m), 748 (m),
698 (vs), 620 cm–1 (w).
1H NMR (400 MHz, DMSO-d6): d = 7.42–7.38 (m, 2 H), 7.33–7.29
(m, 3 H), 7.21–7.10 (m, 7 H), 6.90–6.87 (m, 2 H), 3.31 (s, 2 H),
2.90–2.86 (m, 2 H), 2.48–2.44 (m, 2 H), 2.28 (s, 3 H), 1.58–1.50 (m,
2 H).
13C NMR (100 MHz, DMSO-d6): d = 147.6, 141.1, 139.3, 136.5,
131.2, 130.4, 130.2, 130.1, 129.0, 128.6, 128.5, 128.5, 127.8, 126.4,
120.8, 38.6, 35.8, 24.0, 21.0, 16.4.
MS (EI, 70 eV): m/z (%) = 384 (27), 383 (M+, 100), 205 (28), 182
(15), 124 (13), 115 (11), 91 (51), 44 (11).
HRMS (EI): m/z [M]+ calcd for C26H25NS: 383.1708; found:
383.1699.
4698. (b) Itami, K.; Kamei, T.; Yoshida, J. J. Am. Chem.
Soc. 2003, 125, 14670. (c) Levin, A.; Basheer, A.; Marek, I.
Synlett 2010, 329. (d) Das, J. P.; Chechik, H.; Marek, I. Nat.
Chem. 2009, 1, 128. (e) Zhou, C.; Larock, R. C. Org. Lett.
2005, 7, 259. (f) Alonso, F.; Beletskaya, I. P.; Yus, M.
Chem. Rev. 2004, 104, 3079. (g) Gerard, J.; Hevesi, L.
Tetrahedron 2004, 60, 367. (h) Yasui, H.; Yorimitsu, H.;
Oshima, K. Bull. Chem. Soc. Jpn. 2008, 81, 373. (i) Yasui,
H.; Yorimitsu, H.; Oshima, K. Chem. Lett. 2007, 36, 32.
(j) Kanemura, S.; Kondoh, A.; Yoritmisu, H.; Oshima, K.
Org. Lett. 2007, 9, 2031. (k) Creton, I.; Marek, I.; Brasseur,
D.; Jestin, J.-L.; Normant, J.-F. Tetrahedron Lett. 1994, 35,
6873. (l) Chechik-Lankin, H.; Marek, I. Org. Lett. 2003, 5,
5087.
(4) (a) Murakami, K.; Yorimitsu, H.; Oshima, K. Chem. Eur. J.
2010, 16, 7688. (b) Murakami, K.; Yorimitsu, H.; Oshima,
K. Org. Lett. 2009, 11, 2373.
(5) (a) Knochel, P.; Singer, R. D. Chem. Rev. 1993, 93, 2117.
(b) Knochel, P.; Almena Perea, J. J.; Jones, P. Tetrahedron
1998, 54, 8275.
(6) (a) Rao, S. A.; Knochel, P. J. Am. Chem. Soc. 1991, 113,
5735. (b) Rao, S. A.; Knochel, P. J. Am. Chem. Soc. 1992,
114, 7579.
(5E)-6-(4-Methylphenyl)-6-[(4-methylphenyl)thio]-5-phenyl-
hex-5-enenitrile (9d)
Prepared according to TP5 from 6e (126 mg, 0.3 mmol) and p-
tolylzinc iodide (8b; 0.67 M in THF; 0.6 mL, 0.4 mmol) (reaction
conditions: 25 °C, 5 h). Purification by flash chromatography (pen-
tane–Et2O, 5:1 + 2 vol% Et3N) yielded 9d (94 mg, 82%, E/Z 99:1)
as a white solid; mp 70–71 °C.
IR (diamond-ATR, neat): 2922 (m), 1491 (m), 1454 (m), 1441 (m),
1019 (m), 820 (s), 804 (s), 766 (s), 753 (m), 701 (vs), 681 (m), 638
cm–1 (m).
1H NMR (400 MHz, DMSO-d6): d = 7.18–7.07 (m, 7 H), 6.99–6.94
(m, 4 H), 6.76–6.73 (m, 2 H), 3.08–3.04 (m, 2 H), 2.50–2.47 (m, 2
H), 2.15 (s, 3 H), 2.05 (s, 3 H), 1.59–1.52 (m, 2 H).
13C NMR (100 MHz, DMSO-d6): d = 146.3, 141.3, 136.3, 135.6,
135.5, 132.0, 130.8, 130.4, 129.5, 129.3, 129.1, 128.0, 127.9, 126.7,
120.4, 36.7, 23.9, 20.6, 20.5, 16.0.
MS (EI, 70 eV): m/z (%) = 383 (M+, 100), 260 (83), 219 (41), 204
(22), 69 (28), 57 (35), 43 (50), 41 (23).
HRMS (EI): m/z [M]+ calcd for C26H25NS: 383.1708; found:
383.1694.
(7) (Di)organozinc reagents were prepared according to the
literature: (a) Metzger, A.; Schade, M. A.; Manolikakes, G.;
Knochel, P. Chem. Asian J. 2008, 3, 1678. (b) Metzger, A.;
Schade, M. A.; Knochel, P. Org. Lett. 2008, 10, 1107.
(c) Piller, F. M.; Metzger, A.; Schade, M. A.; Haag, B. A.;
Gavryushin, A.; Knochel, P. Chem. Eur. J. 2009, 15, 7192.
(d) Bernhardt, S.; Metzger, A.; Knochel, P. Synthesis 2010,
3802. (e) Metzger, A.; Bernhardt, S.; Manolikakes, G.;
Knochel, P. Angew. Chem. Int. Ed. 2010, 49, 4665.
(8) (a) Knochel, P.; Yeh, M. C. P.; Berk, S. C.; Talbert, J. J. Org.
Chem. 1988, 53, 2390. (b) Dübner, F.; Knochel, P. Angew.
Chem. Int. Ed. 1999, 38, 379.
(9) Krasovskiy, A.; Knochel, P. Angew. Chem. Int. Ed. 2004, 43,
3333.
(10) Alexakis, A.; Commerçon, A.; Villiéras, J.; Normant, J. F.
Tetrahedron Lett. 1976, 17, 2313.
(11) (a) Rambaud, M.; Villiéras, J. Synthesis 1984, 406.
(b) Villiéras, J.; Rambaud, M. Org. Synth. 1988, 66, 220.
(12) (a) Nakamura, E.; Matsuzawa, S.; Horiguchi, Y.; Kuwajima,
I. Tetrahedron Lett. 1986, 27, 4029. (b) Bourgain-
Commerçon, M.; Foulon, J.-P.; Normant, J. F.
J. Organomet. Chem. 1982, 228, 321.
Acknowledgment
We thank the European Research Council (ERC) for financial sup-
port. We also thank W. C. Heraeus (Hanau), Chemetall GmbH
(Frankfurt) and BASF AG (Ludwigshafen) for the generous gift of
chemicals. E.Z. also thank German Academic Exchange Service
(DAAD) for financial support [programs ‘Michail Lomonosov –
Forschungsstipendien (B)’ (No. A0772362); ‘Forschungs- und
Arbeitsaufenthalte ausländischer Hochschullehrer und Wissen-
schaftler’ (No. A11/044/12)].
(13) Metzger, A.; Piller, F. M.; Knochel, P. Chem. Commun.
2008, 5824.
(14) Stüdemann, T.; Ibrahim-Ouali, M.; Knochel, P. Tetrahedron
1998, 54, 1299.
(15) (a) Negishi, E. Acc. Chem. Res. 1982, 15, 340. (b) Negishi,
E.; Valente, L. F.; Kobayashi, M. J. Am. Chem. Soc. 1980,
102, 3298. (c) Negishi, E.; King, A. O.; Okukado, N. J. Org.
Chem. 1977, 42, 1821.
(16) Walker, S. D.; Barder, T. E.; Martinelli, J. R.; Buchwald, S.
L. Angew. Chem. Int. Ed. 2004, 43, 1871.
(17) (a) Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113,
9585. (b) Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.;
Liebeskind, L. S. J. Org. Chem. 1994, 59, 5905.
(c) Klement, I.; Rottländer, M.; Tucker, C. E.; Majid, T. N.;
Knochel, P.; Venegas, P.; Cahiez, G. Tetrahedron 1996, 52,
7201.
References
(1) Stüdemann, T.; Knochel, P. Angew. Chem., Int. Ed. Engl.
1997, 36, 93.
(2) (a) Normant, J. F.; Alexakis, A. Synthesis 1981, 841.
(b) Robertson, D. W.; Katzenellenbogen, J. A.; Hayes, J. R.;
Katzenellenbogen, B. S. J. Med. Chem. 1982, 25, 167.
(c) Harper, M. J. K.; Walpole, A. L. Nature 1966, 212, 87.
(d) Al-Hassan, M. I. Synth. Commun. 1987, 17, 1247.
(e) Kamei, T.; Tiami, K.; Yoshida, J. Adv. Synth. Catal.
2004, 346, 1824. (f) Reiser, O. Angew. Chem. Int. Ed. 2006,
45, 2838. (g) Abramovitch, A.; Marek, I. Eur. J. Org. Chem.
2008, 4924. (h) Miller, R. B.; Al-Hassan, M. I. J. Org.
Chem. 1985, 50, 2121.
(18) Melzig, L.; Metzger, A.; Knochel, P. Chem. Eur. J. 2011, 17,
2948.
Synthesis 2011, No. 21, 3453–3462 © Thieme Stuttgart · New York