A novel palladium-catalyzed cross-coupling of thiomethylated alkynes with functionalized organozinc reagents

Article abstract of DOI:10.1055/s-0029-1218734

A range of methylthio-substituted acetylenes undergo smooth palladium-catalyzed cross-coupling reactions with functionalized aryl-, heteroaryl-, and alkylzinc reagents using the Pd(OAc)₂/DPE-Phos catalytic system at 25 or 50 C without the need for copper salts. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1218734

PAPER
2085
A Novel Palladium-Catalyzed Cross-Coupling of Thiomethylated Alkynes
with Functionalized Organozinc Reagents
C
ross-Coupling
a
of (Methy
u
lthio)acetylen
r
es
w
ith
i
Organo
n
zinc Reagents Melzig, Jérémy Stemper, Paul Knochel*
Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, Haus F, 81377 München, Germany
Fax +49(89)218077680; E-mail: Paul.Knochel@cup.uni-muenchen.de
Received 20 February 2010; revised 15 March 2010
(Table 1, entry 1). Also heteroarylzinc reagents like 6-
methylpyridin-2-ylzinc iodide (2b) reacted smoothly at
50 °C for four hours with thioalkyne 1a leading to 2-
methyl-6-(phenylethynyl)pyridine (MPEP, 3b), a glutamate
receptor antagonist,12 in 73% yield (entry 2). This method
could also be applied to alkylzinc derivatives. The trifluo-
romethyl-substituted alkyne 1b underwent cross-coupling
with 3-cyanopropylzinc bromide (2c) at 50 °C for four
hours to give hexyne 3c in 66% yield (entry 3). 1-Chloro-
4-[(methylthio)ethynyl]benzene (1c), reacted with 4-cy-
anophenylzinc iodide (2d), providing alkyne 3d in 84%
yield (entry 4). This electrophile also reacted smoothly
with cyclohexylzinc bromide (2e) at 50 °C within 10
hours providing ethynylcyclohexane 3e in 70% yield (en-
try 5). Similarly, the 4-fluoro-substituted ethynylbenzene
1d could be functionalized with zinc reagent 2f, giving
4-chloro-2-[(4-fluorophenyl)ethynyl]-1-methoxybenzene
(3f) in 74% yield (entry 6). Thioalkyne 1d also underwent
a steady cross-coupling with benzofuran-2-ylzinc iodide
(2g) leading to the substituted benzofuran 3g in 82% yield
(entry 7). 1-[(Methylthio)ethynyl]cyclohexene (1e) could
be reacted with the electron-poor arylzinc reagent 2h at 50
°C for six hours to provide (cyclohexenylethynyl)benzene
3h in 76% (entry 8). Similarly, alkylated (methyl-
thio)acetylenes also underwent the cross-coupling. Thus,
the alkynyl thioether 1f was smoothly functionalized with
4-methoxyphenylzinc iodide (2a) at room temperature for
three hours, furnishing hexynylbenzene 3i in 64% (entry
9). Heteroaryl-substituted acetylenes like the pyridine de-
rivative 1g were also suitable for this protocol; reaction of
1g with 2-thienylzinc iodide (2i) at 50 °C for six hours
provided the bis(heteroaryl)acetylene 3j in 72% yield (en-
try 10).
Abstract: A range of methylthio-substituted acetylenes undergo
smooth palladium-catalyzed cross-coupling reactions with func-
tionalized aryl-, heteroaryl-, and alkylzinc reagents using the
Pd(OAc)2/DPE-Phos catalytic system at 25 or 50 °C without the
need for copper salts.
Key words: alkynes, cross-coupling, organometallic reagents, pal-
ladium, zinc
Alkynes are important building blocks in organic synthe-
sis,1 materials science,2 and polymer chemistry.3 Al-
though a variety of preparative approaches are known,4
there is a demand for new synthetic methods. Liebeskind
published an improvement of the Suzuki cross-coupling
protocol which uses thioalkylated acetylenes with a palla-
dium catalyst.5 Similar cross-coupling methods with func-
tionalized organozinc reagents, which are now easily
prepared,6 have recently been described by us.7 Herein we
report a palladium-catalyzed cross-coupling reaction of
substituted organozinc compounds with thiomethylated
alkynes used as electrophiles with Pd(OAc)2/bis[2-
(diphenylphosphino)phenyl] ether (DPE-Phos)8 as the
catalytic system.
The (methylthio)acetylenes could easily be prepared from
terminal alkynes and dimethyl disulfide9 or S-methyl
methanethiosulfonate in good yields.10 All organozinc re-
agents were obtained from the corresponding halides ac-
cording to recent methods.11 The cross-coupling reactions
were performed with Pd(OAc)2 (2.5 mol%) and DPE-
Phos (5.0 mol%) in tetrahydrofuran at 25 or 50 °C for 2–
10 hours (Scheme 1).
R2ZnX⋅LiCl
R1
SMe
R1
R2
64–91%
Interestingly, bis(methylthio)acetylene (1h) could be
cross-coupled using 3.0 equivalents of the organozinc
compound. This is especially useful since the correspond-
ing dihaloacetylenes are known to be explosive, toxic, and
carcinogenic and, hence, not practical substrates.13 Thus,
1h was functionalized with 4-(dimethylamino)phenylzinc
iodide (2j) at room temperature for eight hours giving
4,4¢-ethyne-1,2-diylbis(N,N-dimethylaniline) (3k) in 81%
yield (entry 11). Also 2,4-dichlorophenylzinc iodide (2k)
and the benzofuran derivative 2g could be employed pro-
viding the symmetric diarylacetylenes 3l and 3m in 78%
and 74% yield, respectively (entries 12 and 13).
Pd(OAc)2 (2.5 mol%)
DPE-Phos (5.0 mol%)
THF, 25–50 °C
2–10 h
R1, R2 = aryl, hetaryl, alkyl
Scheme 1 Palladium-catalyzed cross-coupling of thiomethylated
alkynes with functionalized organozinc reagents
Thus, [(methylthio)ethynyl]benzene (1a) was treated with
4-methoxyphenylzinc iodide (2a) at room temperature for
two hours to give the diarylacetylene 3a in 91% yield
SYNTHESIS 2010, No. 12, pp 2085–2091
Advanced online publication: 12.04.2010
DOI: 10.1055/s-0029-1218734; Art ID: T04410SS
x
x.
x
x
.
2
0
1
0
Finally, to show further advantages of this protocol, we
prepared the (methylthio)ethynyl-substituted steroid 1i
© Georg Thieme Verlag Stuttgart · New York

2086
L. Melzig et al.
PAPER
Table 1 Cross-Coupling Reactions of Thiomethylated Alkynes 1 with Functionalized Organozinc Reagents 2
En- Thioalkyne
try
Organozinc reagent
Product
Temp Yielda
time (%)
25°C,
91
OMe
SMe
SMe
MeO
ZnI⋅LiCl
1
2 h
1a
3a
2a
N
N
50°C,
73
ZnI⋅LiCl
2
4 h
1a
2b
3b
F3C
3c
Cl
NC
ZnBr⋅LiCl
F3C
SMe
CN
50°C,
66
3
4 h
2c
1b
Cl
SMe
NC
ZnI⋅LiCl
CN
50°C,
84
4
4 h
1c
3d
Cl
2d
ZnBr⋅LiCl
Cl
SMe
SMe
50°C,
70
5
10 h
1c
2e
3e
OMe
ZnI⋅LiCl
MeO
F
F
50°C,
74
6
4 h
1d
Cl
Cl
2f
3f
O
O
ZnI⋅LiCl
F
F
SMe
50°C,
82
7
6 h
1d
2g
3g
CO2Et
EtO2C
2h
ZnI⋅LiCl
SMe
50°C,
76
8
6 h
1e
3h
Bu
SMe
MeO
ZnI⋅LiCl
Bu
OMe
25°C,
64
9
10
11
3 h
1f
2a
3i
N
N
S
S
50°C,
72
SMe
ZnI⋅LiCl
6 h
2i
1g
3j
MeS
SMe
Me2N
2j
ZnI⋅LiCl Me2N
NMe2
25°C,
81
8 h,
1h
3k
Cl
Cl
Cl
MeS
SMe
SMe
50°C,
78
12
13
Cl
ZnI⋅LiCl
Cl
Cl
4 h
1h
3l
2k
O
O
ZnI⋅LiCl
MeS
50°C,
74
O
3 h
1h
3m
2g
OMOM
OMOM
NMe2
SMe
Me2N
ZnI⋅LiCl
25°C,
75
14
8 h
2j
MOMO
MOMO
1i
3n
a Yield of analytically pure product.
Synthesis 2010, No. 12, 2085–2091 © Thieme Stuttgart · New York

PAPER
Cross-Coupling of (Methylthio)acetylenes with Organozinc Reagents
2087
(3 × 25 mL). The combined organic layers were dried (Na2SO4) and
the solvent was removed in vacuo. The product was purified by
flash column chromatography.
from commercially available ethynylestradiol. This was
readily functionalized using 4-(dimethylamino)phenyl-
zinc iodide (2j) at room temperature within eight hours
and generated the protected ethynylestradiol derivative 3n
in 75% yield (entry 14).
Preparation of Zinc Reagents 2
All aryl- and alkylzinc reagents were prepared according to the lit-
erature.11
In summary, we have developed a novel palladium-cata-
lyzed cross-coupling reaction that uses the commercially
available Pd(OAc)2/DPE-Phos system (2.5 and
5.0 mol%) and takes place at moderate temperatures, fur-
nishing the expected acetylene derivatives in 64–91%
yield. A wide range of functional groups are tolerated and
various classes of zinc reagents (alkyl, aryl, and hetero-
aryl) can be utilized. Further extensions of this method are
currently underway in our laboratories.
Preparation of (Methylthio)acetylenes 1a–i
[(Methylthio)ethynyl]benzene (1a)
According to GP1 using phenylacetylene (5.11 g, 30.0 mmol) in
THF (50.0 mL), 2.42 M n-BuLi in THF (22.7 mL, 55.0 mmol), and
Me2S (5.65 g, 60.0 mmol). Flash chromatographic purification
(silica gel, pentane) yielded 1a (5.89 g, 79%) as a colorless liquid.
1H NMR (300 MHz, CDCl3): d = 2.45 (s, 3 H), 7.25–7.28 (m, 3 H),
7.37–7.40 (m, 2 H).
These data match with the literature.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. Column chromatography was performed using silica gel
(0.040–0.063 mm, 230–400 mesh ASTM) from Merck. Purification
via column chromatography was performed using Merck silica gel
60 (40–63 mm 230–400 mesh ASTM from Merck). All reagents
were obtained from commercial sources. Zn and LiCl were obtained
from Fluka. Melting points were measured using a Büchi B-540 ap-
paratus and are uncorrected. NMR spectra were recorded in CDCl3.
MS spectra and HRMS were recorded using ESI except where oth-
erwise noted.
1-[(Methylthio)ethynyl]-4-(trifluoromethyl)benzene (1b)
According to GP1 using 1-ethynyl-4-(trifluoromethyl)benzene
(5.10 g, 30.0 mmol) in THF (30.0 mL), 2.42 M n-BuLi in THF
(13.6 mL, 33.0 mmol), and Me2S (3.39 g, 36.0 mmol). Flash chro-
matographic purification (silica gel, pentane) yielded 1b (3.24 g,
51%) as a colorless liquid.
IR (ATR): 2932 (vw), 2167 (m), 1613 (m), 1405 (w), 1318 (vs),
1242 (w), 1163 (s), 1120 (s), 1104 (s), 1064 (vs), 1016 (m), 978 (w),
957 (w), 837 (s), 766 (w), 666 (w) cm–1.
1H NMR (300 MHz, CDCl3): d = 2.49 (s, 3 H), 7.45–7.48 (d, J = 8.3
Hz, 2 H), 7.52–7.55 (d, J = 8.3 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 19.3 (CH3), 84.4, 90.8, 123.9 (q,
J = 272.0 Hz, CF3), 125.2 (q, J = 3.9 Hz, CH), 127.2 (q, J = 1.4 Hz),
129.5 (q, J = 32.7 Hz), 131.2 (CH).
(Methylthio)acetylenes 1a–c,e; General Procedure 1
In a dry argon-flushed Schlenk flask equipped with a septum and a
magnetic stirring bar, the acetylene (20.0 mmol) was dissolved in
THF (20.0 mL). The soln was cooled to –78 °C and n-BuLi
(21.0 mmol) was added dropwise. The mixture was stirred at –78 °C
for 10 min, Me2S (22.0 mmol) was added, and the soln was allowed
to warm to r.t. and stirred for 1 h. The mixture was quenched with
sat. aq NH4Cl soln and extracted with EtOAc (3 × 50 mL). The
combined organic layers were dried (Na2SO4) and the solvent was
removed in vacuo. The product was purified by flash column chro-
matography.
MS (EI, 70 eV): m/z (%) = 216 (100), 202 (9), 201 (71), 181 (12),
157 (50), 137 (9), 132 (8), 45 (8), 44 (17), 43 (11).
HRMS (EI): m/z [M]+ calcd for C10H7F332S: 216.0221; found:
216.0217.
1-Chloro-4-[(methylthio)ethynyl]benzene (1c)
According to GP1 using 1-chloro-4-ethynylbenzene (4.10 g,
30.0 mmol) in THF (30.0 mL), 2.42 M n-BuLi in THF (13.6 mL,
33.0 mmol), and Me2S (3.39 g, 36.0 mmol). Flash chromatographic
purification (silica gel, pentane) yielded 1c (4.83 g, 88%) as a col-
orless liquid.
(Methylthio)acetylenes 1d,f,g,i; General Procedure 2
In a dry argon-flushed Schlenk flask equipped with a septum and a
magnetic stirring bar, the acetylene (20.0 mmol) was dissolved in
THF (20.0 mL). The soln was cooled to 0 °C and i-PrMgCl·LiCl
(21.0 mmol) was added dropwise. The mixture was stirred at 0 °C
for 10 min, S-methyl methanethiosulfonate (22.0 mmol) was added,
and the soln was allowed to warm to r.t. and stirred for 1 h. The mix-
ture was quenched with sat. aq NH4Cl soln and extracted with
EtOAc (3 × 50 mL). The combined organic layers were dried
(Na2SO4) and the solvent was removed in vacuo. The product was
purified by flash column chromatography.
IR (ATR): 2927 (w), 2166 (w), 1899 (vw), 1739 (vw), 1590 (vw),
1485 (s), 1432 (w), 1420 (w), 1398 (w), 1312 (w), 1243 (w), 1088
(s), 1013 (m), 976 (m), 957 (w), 867 (w), 823 (vs), 709 (w), 688
cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 2.46 (s, 3 H), 7.24–7.27 (d, J = 8.8
Hz, 2 H), 7.31–7.34 (d, J = 8.8 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 19.3 (CH3), 82.2, 90.7, 121.9,
128.6 (CH), 132.6 (CH), 134.0.
MS (EI, 70 eV): m/z (%) = 185 (3), 184 (33), 183 (9), 182 (100), 169
(25), 168 (6), 167 (72), 132 (12), 125 (7), 123 (20).
HRMS (EI): m/z [M]+ calcd for C9H735Cl32S: 181.9957; found:
181.9949.
Palladium-Catalyzed Cross-Coupling Reaction; General Proce-
dure 3
In a dry argon-flushed Schlenk flask equipped with a septum and a
magnetic stirring bar, the (methylthio)acetylene (1.00 mmol),
Pd(OAc)2 (5.6 mg, 2.5 mol%), and DPE-Phos (27 mg, 5.0 mol%)
were dissolved in THF (1.00 mL). The mixture was stirred for 10
min, the zinc reagent [1.50 mmol (3.00 mmol for products 3k–m)]
was added dropwise, and the mixture was stirred for the given time
at the given temperature (Table 1) until GC analysis of a hydrolyzed
aliquot showed full conversion of the electrophile. The mixture was
quenched with sat. aq. NH4Cl soln and extracted with EtOAc
1-Fluoro-4-[(methylthio)ethynyl]benzene (1d)
According to GP2 using 1-ethynyl-4-fluorobenzene (2.40 g,
20.0 mmol) in THF (20.0 mL), 1.19 M i-PrMgCl·LiCl in THF
(18.5 mL, 22.0 mmol), and S-methyl methanethiosulfonate (3.03 g,
24.0 mmol). Flash chromatographic purification (silica gel, pen-
tane) yielded 1d (2.77 g, 83%) as a yellow liquid.
Synthesis 2010, No. 12, 2085–2091 © Thieme Stuttgart · New York

2088
L. Melzig et al.
PAPER
IR (ATR): 2928 (w), 2170 (w), 1739 (w), 1600 (m), 1501 (vs), 1434
(w), 1423 (w), 1313 (w), 1230 (s), 1217 (s), 1155 (m), 1092 (w),
1013 (w), 977 (w), 957 (w), 873 (w), 831 (vs), 794 (s), 692 cm–1
(vw).
1H NMR (300 MHz, CDCl3): d = 2.46 (s, 3 H), 6.95–7.01 (m, 2 H),
7.36–7.41 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 19.3 (CH3), 80.59, 90.7, 115.5 (d,
J = 22.2 Hz, CH), 119.5 (d, J = 3.4 Hz), 133.5 (d, J = 8.5 Hz, CH),
162.4 (d, J = 249.5 Hz, CF).
Bis(methylthio)acetylene (1h)
Thioether 1h was prepared according to Brandsma et al.16 from 18%
sodium acetylide in xylene (53.4 g, 200 mmol) dissolved in THF
(100 mL). The soln was cooled to 0 °C and methyl thiocyanate
(14.6 g, 200 mmol) was added slowly. The mixture was stirred at
r.t. for 1 h and then the reaction was quenched with sat. aq K2CO3
soln (200 mL) and extracted with Et2O (2 × 200 mL). Fractional
distillation (15 mbar) yielded 1h (6.44 g, 55%) as a colorless liquid.
1H NMR (300 MHz, CDCl3): d = 2.36 (s, 6 H).
These data match with the literature.16
MS (EI, 70 eV): m/z (%) = 166 (100), 152 (11), 151 (74), 107 (84),
69 (10), 57 (14), 55 (12), 44 (17), 43 (20), 41 (12).
HRMS (EI): m/z [M]+ calcd for C9H7F32S: 166.0252; found:
166.0246.
3,17b-Bis(methoxymethoxy)-17a-[(methylthio)ethynyl]estra-
1(10),2,4-triene (1i)
According to GP2 using MOM-protected ethynylestradiol17 (2.11 g,
5.48 mmol) in THF (10.0 mL), 1.19 M i-PrMgCl·LiCl in THF
(5.07 mL, 6.03 mmol), and S-methyl methanethiosulfonate
(830 mg, 6.58 mmol). Flash chromatographic purification (silica
gel, pentane–Et2O, 10:1) yielded 1i (1.96 g, 83%) as a colorless oil.
1-[(Methylthio)ethynyl]cyclohexene (1e)
According to GP1 using 1-ethynylcyclohexene (3.18 g, 30.0 mmol)
in THF (30.0 mL), 2.42 M n-BuLi in THF (13.6 mL, 33.0 mmol),
and Me2S (3.39 g, 36.0 mmol). Flash chromatographic purification
(silica gel, pentane) yielded 1e (3.90 g, 85%) as a colorless liquid.
IR (ATR): 2928 (m), 2162 (vw), 1739 (vw), 1497 (m), 1440 (w),
1241 (m), 1231 (m), 1150 (s), 1094 (m), 1076 (m), 1033 (s), 1015
(vs), 920 (m), 871 (w), 819 (w), 735 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 0.90 (s, 3 H), 1.35–1.51 (m, 4 H),
1.71–1.83 (m, 4 H), 1.85–1.89 (m, 1 H), 2.11–2.17 (m, 1 H), 2.20–
2.25 (m, 2 H), 2.30–2.35 (m, 1 H), 2.40 (s, 3 H), 2.84–2.86 (m, 2 H),
3.40 (s, 3 H), 3.47 (s, 3 H), 4.79 (d, J = 6.5 Hz, 1 H), 5.02 (d, J = 6.5
Hz, 1 H), 5.14 (s, 2 H), 6.77 (d, J = 2.6 Hz, 1 H), 6.83 (dd, J = 8.4,
2.6 Hz, 1 H), 7.20 (d, J = 8.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 13.1 (CH3), 19.4 (CH3), 23.0
(CH2), 26.3 (CH2), 27.2 (CH2), 29.7 (CH2), 33.3 (CH2), 37.5 (CH2),
39.1 (CH), 43.6 (CH), 48.2, 48.9 (CH), 55.7 (CH3), 55.8 (CH3),
79.7, 86.1, 93.4 (CH2), 93.5, 94.4 (CH2), 113.7 (CH), 116.1 (CH),
126.3 (CH), 133.8, 138.0, 155.0.
IR (ATR): 2925 (vs), 2857 (m), 2830 (m), 1739 (w), 1626 (vw),
1446 (m), 1434 (s), 1348 (m), 1311 (m), 1136 (w), 1077 (w), 1045
(w), 975 (m), 956 (m), 918 (s), 840 (s), 802 (m), 797 (m), 706 cm–1
(w).
1H NMR (300 MHz, CDCl3): d = 1.51–1.65 (m, 4 H), 2.04–2.13 (m,
4 H), 2.37 (s, 3 H), 6.05–6.09 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 19.6 (CH3), 21.5 (CH2), 22.3
(CH2), 25.7 (CH2), 29.2 (CH2), 77.5, 93.7, 120.9, 134.9 (CH).
MS (EI, 70 eV): m/z (%) = 152 (51), 137 (61), 109 (100), 105 (43),
104 (39), 103 (56), 97 (50), 93 (54), 91 (59), 77 (39).
HRMS (EI): m/z [M]+ calcd for C9H1232S: 152.0660; found:
152.0653.
MS (EI, 70 eV): m/z (%) = 416 (13), 415 (45), 385 (12), 383 (38),
339 (15), 272 (12), 173 (10), 17 (11), 85 (13), 45 (100).
HRMS (EI): m/z [M]+ calcd for C25H34O432S: 430.2178; found:
430.2178.
1-(Methylthio)hex-1-yne (1f)
According to GP2 using hex-1-yne (1.64 g, 20.0 mmol) in THF
(20.0), 1.19 M i-PrMgCl·LiCl in THF (18.5 mL, 22.0 mmol), and S-
methyl methanethiosulfonate (3.03 g, 24.0 mmol). Flash chromato-
graphic purification (silica gel, pentane) yielded 1f (2.33 g, 91%) a
colorless liquid.
1H NMR (300 MHz, CDCl3): d = 0.88 (t, J = 6.8 Hz, 3 H), 1.32–1.50
(m, 4 H), 2.26 (t, J = 6.8 Hz, 2 H), 2.35 (s, 3 H).
Preparation of Substituted Acetylenes 3a–n
1-Methoxy-4-(phenylethynyl)benzene (3a)
According to GP3 using thioether 1a (148 mg, 1.00 mmol) in THF
(1.00 mL) and 0.93 M 4-methoxyphenylzinc iodide (2a) in THF
(1.29 mL, 1.50 mmol). Flash chromatographic purification (silica
gel, pentane–Et2O, 40:1) yielded 3a (189 mg, 91%) as a white solid;
mp 70.8–72.5 °C.
These data match with the literature.15
2-[(Methylthio)ethynyl]pyridine (1g)
IR (ATR): 3010 (w), 2838 (w), 2360 (m), 2341 (m), 2213 (w), 1604
(m), 1592 (m), 1507 (s), 1457 (m), 1439 (m), 1286 (m), 1246 (vs),
1174 (s), 1137 (m), 1107 (m), 1025 (s), 836 (vs), 779 (m), 752 (vs),
688 (s), 668 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 3.82 (s, 3 H), 6.86–6.89 (d, J = 8.9
Hz, 2 H), 7.28–7.33 (m, 3 H), 7.46 (d, J = 8.9 Hz, 2 H), 7.48–7.50
(m, 2 H).
13C NMR (75 MHz, CDCl3): d = 55.3 (CH3), 88.1, 89.4, 114.0 (CH),
115.4, 123.6, 127.9 (CH), 128.3 (CH), 131.4 (CH), 133.0 (CH),
159.6.
According to GP2 using 2-ethynylpyridine (3.09 g, 30.0 mmol) in
THF (30.0 mL), 1.19 M i-PrMgCl·LiCl in THF (27.7 mL,
33.0 mmol), and S-methyl methanethiosulfonate (4.55 g,
36.0 mmol). Flash chromatographic purification (silica gel. pen-
tane–Et2O, 2:1) yielded 1g (2.12 g, 47%) as a colorless liquid.
IR (ATR): 3040 (w), 3002 (w), 2926 (w), 2170 (m), 2131 (w), 1739
(w), 1638 (w), 1579 (s), 1560 (m), 1508 (m), 1459 (s), 1424 (s),
1312 (m), 1258 (m), 1148 (m), 1080 (m), 988 (m), 823 (w), 773
(vs), 738 (m), 664 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 2.48 (dd, J = 1.1, 0.4 Hz, 3 H),
7.13–7.18 (m, 1 H), 7.31–7.34 (m, 1 H), 7.56–7.62 (m, 1 H), 8.50–
8.52 (m, 1 H).
MS (EI, 70 eV): m/z (%) = 208 (100), 194 (10), 193 (64), 165 (46),
164 (12), 163 (11), 139 (11), 69 (9), 57 (11), 43 (22).
HRMS (EI): m/z [M]+ calcd for C15H12O: 208.0888; found:
208.874.
13C NMR (75 MHz, CDCl3): d = 19.0 (CH3), 83.0, 91.6, 122.3 (CH),
126.2 (CH), 136.1 (CH), 143.18, 149.7 (CH).
MS (EI, 70 eV): m/z (%) = 149 (92), 148 (100), 134 (55), 83 (33),
69 (42), 57 (41), 55 (44), 44 (56), 43 (36), 40 (35).
HRMS (EI): m/z [M]+ calcd for C8H7N32S: 149.0299; found:
149.0283.
2-Methyl-6-(phenylethynyl)pyridine (3b)
According to GP3 using thioether 1a (148 mg, 1.00 mmol) in THF
(1.00 mL) and 0.44 M 6-methylpyridin-2-ylzinc iodide (2b) in THF
Synthesis 2010, No. 12, 2085–2091 © Thieme Stuttgart · New York

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Cross-Coupling of (Methylthio)acetylenes with Organozinc Reagents
2089
(3.41 mL, 1.50 mmol). Flash chromatographic purification (silica
HRMS (EI): m/z [M]+ calcd for C14H1535Cl: 218.0862; found:
gel, pentane–Et2O, 8:2) yielded 3b (141 mg, 73%) as a clear oil.
218.0859.
1H NMR (300 MHz, CDCl3): d = 2.55 (s, 3 H), 7.03–7.09 (m, 1 H),
4-Chloro-2-[(4-fluorophenyl)ethynyl]-1-methoxybenzene (3f)
According to GP3 using thioether 1d (166 mg, 1.00 mmol) in THF
(1.00 mL) and 0.84 M 5-chloro-2-methoxyphenylzinc iodide (2f) in
THF (1.79 mL, 1.50 mmol). Flash chromatographic purification
(silica gel, pentane) yielded 3f (192 mg, 74%) as a yellow oil.
7.30–7.37 (m, 4 H), 7.52–7.61 (m, 3 H).
These data match with the literature.18
6-[4-(Trifluoromethyl)phenyl]hex-5-ynenitrile (3c)
According to GP3 using thioether 1b (216 mg, 1.00 mmol) in THF
(1.00 mL) and 1.02 M 3-cyanopropylzinc bromide (2c) in THF
(1.47 mL, 1.50 mmol). Flash chromatographic purification (silica
gel, pentane–Et2O, 9:1) yielded 3c (156 mg, 66%) as a clear oil.
IR (ATR): 2939 (w), 2844 (vw), 2360 (vw), 1738 (w), 1591 (w),
1508 (vs), 1486 (s), 1462 (m), 1397 (m), 1282 (s), 1263 (m), 1242
(s), 1224 (vs), 1154 (m), 1122 (s), 1024 (s), 896 (m), 833 (vs), 804
(s), 769 (m), 676 cm–1 (w).
IR (ATR): 2942 (vw), 2361 (vw), 2248 (w), 2166 (m), 1740 (vw),
1612 (m), 1598 (w), 1491 (m), 1444 (w), 1431 (w), 1346 (w), 1321
(vs), 1102 (s), 1070 (w), 1026 (vw), 917 (w), 758 (vs), 690 (vs), 669
cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 1.97 (dt, J = 6.8, 7.2 Hz, 2 H), 2.55
(t, J = 7.2 Hz, 2 H), 2.62 (t, J = 6.8 Hz, 2 H), 7.48 (d, J = 8.5 Hz, 2
H), 7.55 (d, J = 8.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 16.3 (CH2), 18.5 (CH2), 24.4
(CH2), 81.2, 89.7, 123.9 (q, J = 272.1 Hz, CF3), 119.0, 125.2 (q,
J = 3.9 Hz, CH), 127.0 (q, J = 1.6 Hz), 129.8 (q, J = 32.6 Hz), 131.8
(CH).
1H NMR (300 MHz, CDCl3): d = 3.88 (s, 3 H), 6.81 (d, J = 8.9 Hz,
1 H), 6.99–7.01 (m, 2 H), 7.24 (dd, J = 8.9, 2.7 Hz, 1 H), 7.44 (d,
J = 2.7 Hz, 1 H), 7.48–7.55 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 56.1 (CH3), 84.1, 93.3, 111.9 (CH),
113.9, 115.6 (d, J = 22.2 Hz, CH), 119.2 (d, J = 3.6 Hz), 125.2,
129.5 (CH), 132.8 (CH), 133.6 (d, J = 8.5 Hz, CH), 158.6, 162.6 (d,
J = 250.0 Hz, CF).
MS (EI, 70 eV): m/z (%) = 261 (31), 260 (81), 259 (55), 217 (72),
197 (32), 196 (57), 182 (74), 181 (100), 167 (33), 165 (91).
HRMS (EI): m/z [M]+ calcd for C15H1035ClFO: 260.0404; found:
260.0384.
MS (EI, 70 eV): m/z (%) = 237 (100), 236 (45), 218 (26), 197 (25),
196 (61), 183 (96), 177 (58), 168 (35), 133 (24), 43 (94).
HRMS (EI): m/z [M]+ calcd for C13H10F3N: 237.0765; found:
237.0754.
2-[(4-Fluorophenyl)ethynyl]benzofuran (3g)
According to GP3 using thioether 1d (166 mg, 1.00 mmol) in THF
(1.00 mL) and 0.70 M benzofuran-2-ylzinc iodide (2g) in THF
(2.14 mL, 1.50 mmol). Flash chromatographic purification (silica
gel, pentane) yielded 3g (194 mg, 82%) as a white solid; mp 94.8–
96.2 °C.
4-[(4-Chlorophenyl)ethynyl]benzonitrile (3d)
According to GP3 using thioether 1c (182 mg, 1.00 mmol) in THF
(1.00 mL) and 0.71 M 4-cyanophenylzinc iodide (2d) in THF
(2.11 mL, 1.50 mmol). Flash chromatographic purification (silica
gel, pentane–Et2O, 20:1) yielded 3d (198 mg, 84%) as a white solid;
mp 179.4–180.5 °C.
IR (ATR): 2360 (w), 1896 (w), 1739 (w), 1598 (w), 1564 (m), 1498
(m), 1469 (m), 1448 (m), 1440 (m), 1346 (w), 1302 (w), 1256 (w),
1210 (m), 1168 (m), 1155 (m), 948 (m), 835 (vs), 812 (vs), 749 (vs),
736 cm–1 (s).
1H NMR (300 MHz, CDCl3): d = 7.00 (d, J = 1.0 Hz, 1 H), 7.04–
7.11 (m, 2 H), 7.23–7.29 (m, 1 H), 7.31–7.38 (m, 1 H), 7.46–7.50
(m, 1 H), 7.53–7.60 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 79.4, 93.9, 111.2 (CH), 111.6
(CH), 115.9 (d, J = 22.17 Hz, CH), 118.0 (d, J = 3.6 Hz), 121.2
(CH), 123.3 (CH), 125.6 (CH), 127.7, 133.7 (d, J = 8.8 Hz, CH),
138.6, 154.9, 162.0 (d, J = 251.3 Hz, CF).
IR (ATR): 2229 (m), 2216 (w), 1739 (m), 1604 (m), 1590 (w), 1498
(m), 1484 (m), 1406 (m), 1398 (m), 1366 (m), 1229 (m), 1217 (m),
1090 (m), 1080 (m), 1012 (m), 827 (vs), 770 (w), 679 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 7.32–7.37 (m, 2 H), 7.44–7.49 (m,
2 H), 7.57–7.60 (m, 2 H), 7.62–7.65 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 88.6, 92.5, 111.7, 118.4, 120.7,
127.9, 128.9 (CH), 132.0 (CH), 132.1 (CH), 133.0 (CH), 135.3.
MS (EI, 70 eV): m/z (%) = 239 (31), 238 (18), 237 (100), 202 (11),
201 (25), 176 (9), 175 (16), 119 (5), 87 (10), 42 (6).
HRMS (EI): m/z [M]+ calcd for C15H835ClN: 237.345; found:
237.0333.
MS (EI, 70 eV): m/z (%) = 238 (2), 237 (15), 236 (100), 208 (6), 207
(36), 206 (3), 187 (2), 182 (2), 104 (1), 44 (3).
HRMS (EI): m/z [M]+ calcd for C16H9FO: 236.0637; found:
236.0643.
1-Chloro-4-(cyclohexylethynyl)benzene (3e)
Ethyl 4-(Cyclohex-1-enylethynyl)benzoate (3h)
According to GP3 using thioether 1c (182 mg, 1.00 mmol) in THF
(1.00 mL) and 0.95 M cyclohexylzinc bromide (2e) in THF
(1.58 mL, 1.50 mmol). Flash chromatographic purification (silica
gel, pentane) yielded 3e (153 mg, 70%) as a yellow oil.
According to GP3 using thioether 1e (152 mg, 1.00 mmol) in THF
(1.00 mL) and 0.63 M 4-(ethoxycarbonyl)phenylzinc iodide (2h) in
THF (2.38 mL, 1.50 mmol). Flash chromatographic purification
(silica gel, pentane–Et2O, 9:1) yielded 3h (194 mg, 76%) as a white
solid; mp 80.1–82.2 °C.
IR (ATR): 2931 (m), 2855 (m), 2230 (vw), 1899 (vw), 1738 (w),
1592 (vw), 1489 (s), 1447 (m), 1398 (w), 1304 (w), 1089 (s), 1028
(w), 1014 (m), 952 (w), 933 (w), 826 (vs), 798 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 1.30–1.41 (m, 2 H), 1.46–1.57 (m,
4 H), 1.69–1.79 (m, 2 H), 1.83–1.91 (m, 2 H), 2.52–2.61 (m, 1 H),
7.21–7.25 (m, 2 H), 7.29–7.33 (m, 2 H).
IR (ATR): 2937 (w), 2196 (w), 1714 (vs), 1601 (m), 1403 (m), 1367
(m), 1283 (s), 1272 (vs), 1238 (m), 1176 (m), 1129 (m), 1104 (m),
1094 (m), 1028 (m), 1016 (m), 856 (m), 766 (s), 694 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 1.38 (t, J = 7.1 Hz, 3 H), 1.57–1.72
(m, 4 H), 2.12–2.24 (m, 4 H), 4.36 (q, J = 7.1 Hz, 2 H), 6.24–6.27
(m, 1 H), 7.43–7.47 (m, 2 H), 7.94–7.98 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 14.3 (CH3), 21.5 (CH2), 22.3
(CH2), 25.8 (CH2), 29.7 (CH2), 61.0 (CH2), 86.2, 94.3, 120.5, 128.5,
129.4 (CH), 131.3 (CH), 136.4 (CH), 166.2 (CH).
13C NMR (75 MHz, CDCl3): d = 24.9 (CH2), 25.9(CH2), 29.7 (CH),
32.6 (CH2), 79.5, 95.5, 122.7, 128.4 (CH), 132.8 (CH), 133.3.
MS (EI, 70 eV): m/z (%) = 218 (90), 189 (52), 183 (50), 175 (66),
155 (54), 141 (100), 136 (36), 129 (49), 127 (40), 125 (74).
Synthesis 2010, No. 12, 2085–2091 © Thieme Stuttgart · New York

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L. Melzig et al.
PAPER
MS (EI, 70 eV): m/z (%) = 254 (100), 226 (10), 209 (24), 182 (9),
HRMS (EI): m/z [M]+ calcd for C18H20N2: 264.1626; found:
181 (49), 180 (8), 166 (30), 165 (21), 153 (11), 152 (16).
264.1617.
HRMS (EI): m/z [M]+ calcd for C17H18O2: 254.1307; found:
254.1298.
1,1¢-Ethyne-1,2-diylbis(2,4-dichlorobenzene) (3l)
According to GP3 using thioether 1h (118 mg, 1.00 mmol) in THF
(1.00 mL) and 0.63 M 2,4-dichlorophenylzinc iodide (2k) in THF
(4.76 mL, 3.00 mmol). Flash chromatographic purification (silica
gel, pentane) yielded 3l (246 mg, 78%) as a white solid; mp 132.4–
133.8 °C.
1-(Hex-1-ynyl)-4-methoxybenzene (3i)
According to GP3 using thioether 1f (128 mg, 1.00 mmol) in THF
(1.00 mL) and 0.93 M 4-methoxyphenylzinc iodide (2a) in THF
(1.29 mL, 1.50 mmol). Flash chromatographic purification (silica
gel, pentane–Et2O, 50:1) yielded 3i (120 mg, 64%) as a yellow oil.
IR (ATR): 1739 (w), 1722 (w), 1587 (w), 1544 (w), 1487 (s), 1471
(m), 1462 (m), 1426 (w), 1378 (m), 1230 (w), 1217 (w), 1141 (w),
1096 (s), 1051 (m), 873 (w), 859 (s), 816 (vs), 810 (vs), 737 cm–1
(s).
1H NMR (300 MHz, CDCl3): d = 7.24 (dd, J = 2.2, 8.4 Hz, 2 H),
7.46 (d, J = 2.2 Hz, 2 H), 7.51 (d, J = 8.4 Hz, 2 H).
IR (ATR): 2957 (w), 2932 (m), 1739 (w), 1607 (m), 1508 (s), 1464
(m), 1442 (w), 1378 (w), 1288 (m), 1242 (vs), 1218 (w), 1171 (m),
1106 (w), 1033 (s), 829 (s), 809 (m), 800 (w), 794 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 0.94 (t, J = 7.2 Hz, 3 H), 1.41–1.63
(m, 4 H), 2.38 (t, J = 6.9 Hz, 2 H), 3.78 (s, 3 H), 6.78–6.82 (m, 2 H),
7.30–7.34 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 13.6 (CH3), 19.1 (CH2), 22.0
(CH2), 31.0 (CH2), 55.2 (CH3), 80.2, 88.7, 113.8 (CH), 116.3, 132.8
(CH), 159.0.
13C NMR (75 MHz, CDCl3): d = 91.0, 121.3, 127.1 (CH), 129.5
(CH), 134.0 (CH), 135.2, 136.8.
MS (EI, 70 eV): m/z (%) = 314 (100), 246 (18), 245 (6), 244 (31),
174 (8), 158 (11), 157 (8), 123 (8), 122 (11), 104 (7).
MS (EI, 70 eV): m/z (%) = 188 (100), 187 (19), 173 (56), 159 (44),
HRMS (EI): m/z [M]+ calcd for C14H635Cl4: 313.9224; found:
158 (33), 146 (15), 145 (30), 144 (15), 115 (18), 102 (16).
313.9216.
HRMS (EI): m/z [M]+ calcd for C13H16O: 188.1201; found:
188.1193.
2,2¢-Ethyne-1,2-diylbis(benzofuran) (3m)
According to GP3 using thioether 1h (118 mg, 1.00 mmol) in THF
(1.00 mL) and 0.70 M benzofuran-2-ylzinc iodide (2g) in THF
(4.29 mL, 3.00 mmol). Flash chromatographic purification (silica
gel, pentane–CH2Cl2, 40:1) yielded 3m (191 mg, 74%) as a white
solid; mp 138.6–140.1 °C.
2-(2-Thienylethynyl)pyridine (3j)
According to GP3 using thioether 1g (149 mg, 1.00 mmol) in THF
(1.00 mL) and 0.79 M 2-thienylzinc iodide (2i) in THF (1.90 mL,
1.50 mmol). Flash chromatographic purification (silica gel, pen-
tane–Et2O, 7:3) yielded 3j (133 mg, 72%) as a yellow solid; mp
55.4–56.8 °C.
IR (ATR): 1739 (w), 1450 (m), 1442 (m), 1349 (m), 1296 (m), 1254
(m), 1200 (m), 1160 (m), 1142 (m), 1104 (w), 1012 (w), 960 (m),
931 (m), 885 (w), 833 (m), 826 (m), 799 (m), 746 (vs), 735 (s), 692
cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 7.13 (s, 1 H), 7.25–7.40 (m, 2 H),
7.50 (d, J = 7.4 Hz, 1 H), 7.60 (d, J = 7.2 Hz, 1 H).
IR (ATR): 3103 (w), 2204 (m), 1739 (w), 1578 (m), 1560 (m), 1459
(m), 1432 (m), 1416 (m), 1276 (w), 1212 (m), 1152 (m), 1125 (w),
1045 (w), 987 (w), 853 (m), 835 (m), 776 (s), 738 (w), 706 (vs), 669
cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 7.03 (dd, J = 5.2, 3.6 Hz, 1 H),
7.27–7.30 (m, 1 H), 7.35 (dd, J = 5.2, 1.1 Hz, 1 H), 7.41 (dd, J = 3.6,
1.1 Hz, 1 H), 7.51–7.54 (m, 1 H), 7.73 (ddd, J = 7.9, 7.7, 1.9 Hz, 1
H), 8.61–8.63 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 87.8, 91.5, 121.9, 122.9 (CH),
127.1 (CH), 127.3 (CH), 128.7 (CH), 133.7 (CH), 136.9 (CH),
142.6, 149.3 (CH).
13C NMR (75 MHz, CDCl3): d = 85.2, 111.4 (CH), 113.2 (CH),
121.5 (CH), 123.5 (CH), 126.2 (CH), 127.4, 137.6, 155.2.
MS (EI, 70 eV): m/z (%) = 260 (2), 259 (17), 258 (100), 234 (4), 229
(5), 202 (5), 201 (4), 200 (5), 129 (3), 88 (2).
HRMS (EI): m/z [M]+ calcd for C18H10O2: 258.0681; found:
258.0675.
MS (EI, 70 eV): m/z (%) = 185 (100), 184 (9), 159 (8), 158 (5), 152
(5), 141 (7), 140 (8), 114 (4), 113 (4), 79 (6).
4-{[3,17b-Bis(methoxymethoxy)estra-1(10),2,4-trien-17a-
yl]ethynyl}-N,N-dimethylaniline (3n)
According to GP3 using thioether 1i (152 mg, 1.00 mmol) in THF
(1.00 mL) and 0.99 M 4-(dimethylamino)phenylzinc iodide (2j) in
THF (1.52 mL, 1.50 mmol). Flash chromatographic purification
(silica gel, pentane–Et2O, 7:3) yielded 3n (377 mg, 75%) as a yel-
low oil.
HRMS (EI): m/z [M]+ calcd for C11H7N32S: 185.0299; found:
185.0284.
4,4¢-Ethyne-1,2-diylbis(N,N-dimethylaniline) (3k)
According to GP3 using thioether 1h (118 mg, 1.00 mmol) in THF
(1.00 mL) and 0.99 M 4-(dimethylamino)phenylzinc iodide (2j) in
THF (3.03 mL, 3.00 mmol). Flash chromatographic purification
(silica gel, pentane–CH2Cl2, 6:4) yielded 3k (215 mg, 81%) as a
yellow solid; mp 232.2–234.0 °C.
IR (ATR): 2928 (m), 2360 (w), 2213 (vw), 1739 (w), 1607 (s), 1520
(s), 1497 (m), 1444 (m), 1357 (m), 1230 (m), 1150 (s), 1075 (s),
1061 (m), 1014 (vs), 972 (m), 945 (m), 919 (m), 871 (w), 815 (s),
784 (w), 730 cm–1 (m).
IR (ATR): 2890 (w), 2807 (w), 2361 (w), 1739 (w), 1608 (s), 1526
(s), 1480 (m), 1444 (m), 1352 (s), 1321 (m), 1227 (s), 1190 (s), 1164
(m), 1137 (m), 1062 (m), 941 (m), 827 (m), 816 (vs) cm–1.
1H NMR (300 MHz, CDCl3): d = 2.97 (s, 12 H), 6.63–6.68 (m, 4 H),
7.36–7.41 (m, 4 H).
13C NMR (75 MHz, CDCl3): d = 40.3 (CH3), 88.1, 111.2, 111.9
(CH), 132.3 (CH), 149.7.
1H NMR (600 MHz, CDCl3): d = 0.97 (s, 3 H), 1.36–1.56 (m, 4 H),
1.83–1.92 (m, 4 H), 2.03–2.08 (m, 1 H), 2.20–2.28 (m, 2 H), 2.34–
2.39 (m, 2 H), 2.84–2.89 (m, 2 H), 2.97 (s, 6 H), 3.45 (s, 3 H), 3.49
(s, 3 H), 4.89 (d, J = 6.3 Hz, 1 H), 5.14 (d, J = 6.3 Hz, 1 H), 5.16 (s,
2 H), 6.63–6.66 (m, 2 H), 6.79 (d, J = 2.7 Hz, 1 H), 6.85 (dd, J = 8.8,
2.7 Hz, 1 H), 7.24 (d, J = 8.8 Hz, 1 H), 7.34–7.36 (m, 2 H).
13C NMR (150 MHz, CDCl3): d = 13.1 (CH3), 23.0 (CH2), 26.4
(CH2), 27.2 (CH2), 29.8 (CH2), 33.4 (CH2), 37.7 (CH2), 39.2 (CH),
40.2 (CH3), 43.6 (CH), 48.1, 49.0 (CH), 55.7 (CH3), 55.8 (CH3),
85.9, 87.6, 89.0, 93.6 (CH2), 94.4 (CH2), 111.8, 113.6 (CH), 116.1
MS (EI, 70 eV): m/z (%) = 265 (19), 264 (100), 263 (6), 250 (5), 249
(20), 248 (12), 247 (4), 233 (4), 132 (5), 131 (6).
Synthesis 2010, No. 12, 2085–2091 © Thieme Stuttgart · New York

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Cross-Coupling of (Methylthio)acetylenes with Organozinc Reagents
2091
(CH), 126.3 (CH), 132.7 (CH), 132.8 (CH), 134.0, 138.0, 150.0,
154.9.
Schade, M. A.; Knochel, P. Org. Lett. 2008, 10, 1107.
(e) Dong, Z.; Clososki, G. C.; Wunderlich, S. H.; Unsinn, A.;
Li, J.; Knochel, P. Chem. Eur. J. 2009, 15, 457. (f) Mosrin,
M.; Monzon, G.; Bresser, T.; Knochel, P. Chem. Commun.
2009, 5615. (g) Piller, F. M.; Metzger, A.; Schade, M. A.;
Haag, B. A.; Gavryushin, A.; Knochel, P. Chem. Eur. J.
2009, 15, 7192. (h) Metzger, A.; Argyo, C.; Knochel, P.
Synthesis 2010, 882.
MS (EI, 70 eV): m/z (%) = 460 (22), 459 (69), 458 (32), 443 (46),
442 (46), 441 (100), 201 (20), 200 (40), 148 (50), 45 (21).
HRMS (EI): m/z [M]+ calcd for C32H41NO4: 503.3036; found:
503.3035.
(7) Metzger, A.; Melzig, L.; Despotopoulou, C.; Knochel, P.
Acknowledgment
Org. Lett. 2009, 11, 4228.
(8) Kranenburg, M.; van der Burgt, Y. E. M.; Kamer, P. C. J.;
Goubitz, K.; Fraanje, J.; van Leeuwen, P. W. N. M.
Organometallics 1995, 14, 3081.
(9) Woodgate, P. D.; Sutherland, H. S.; Rickard, C. E. F.
J. Organomet. Chem. 2001, 627, 206.
We thank the DFG and the European Research Council (ERC) for
financial support. We thank Chemetall GmbH (Frankfurt) and
BASF SE (Ludwigshafen) for the generous gift of chemicals.
(10) Kopp, F.; Sklute, G.; Polborn, K.; Marek, I.; Knochel, P.
References
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(11) Krasovskiy, A.; Malakhov, V.; Gavryushin, A.; Knochel, P.
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(4) Preparative Acetylenic Chemistry; Brandsma, L., Ed.;
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Synthesis 2010, No. 12, 2085–2091 © Thieme Stuttgart · New York