Silylcupration and copper-catalyzed carbomagnesiation of ynamides: Application to aza-Claisen rearrangement

Article abstract of DOI:10.1246/bcsj.81.373

Treatment of ynamides with silylcopper reagents resulted in silylcupration to afford (E)-ss-silylenamides, after protonolysis, in good yields with high regio- and stereoselectivity. Reaction of ynamides having an allyl group on the nitrogen with Grignard reagents in the presence of a copper catalyst resulted in carbomagnesiation across the alkynyl unit and subsequent heating provided 4-pentenenitriles via aza-Claisen rearrangement.

Full text of DOI:10.1246/bcsj.81.373

Ó 2008 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 81, No. 3, 373–379 (2008)
373
Silylcupration and Copper-Catalyzed Carbomagnesiation of Ynamides:
Application to Aza-Claisen Rearrangement
ꢀ
ꢀ
Hiroto Yasui, Hideki Yorimitsu, and Koichiro Oshima
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510
Received October 29, 2007; E-mail: yori@orgrxn.mbox.media.kyoto-u.ac.jp
Treatment of ynamides with silylcopper reagents resulted in silylcupration to afford (E)-ꢀ-silylenamides, after pro-
tonolysis, in good yields with high regio- and stereoselectivity. Reaction of ynamides having an allyl group on the nitro-
gen with Grignard reagents in the presence of a copper catalyst resulted in carbomagnesiation across the alkynyl unit and
subsequent heating provided 4-pentenenitriles via aza-Claisen rearrangement.
Ynamides are ynamines having sufficient stability to pre-
pare and handle due to the electron-withdrawing group on the
nitrogen. Since direct and convenient synthesis of ynamides
was accomplished, organic reactions of ynamides have been
studied actively.1 Among them, addition reactions of organo-
metallic reagents to ynamides have been well investigated.2
We report here highly regio- and stereoselective silylcupration
of ynamides. We also describe copper-catalyzed carbomagne-
siation reactions of ynamides having an allyl group followed
by aza-Claisen rearrangement.3
to Hsung’s method.7 Treatment of N-monosubstituted arene-
sulfonamides and 1-bromo-1-alkyne in the presence of potas-
sium carbonate and catalytic amounts of CuSO4 5H2O and
ꢁ
1,10-phenanthroline at 60 ꢂC in toluene provided the corre-
sponding ynamides 1 in good yields (Scheme 1).
Reaction of N-1-propynylamide 1a with Me3SiCu, prepared
by Me3SiLi and CuBr SMe2, furnished the corresponding
ꢁ
products 2a and 3a in 77% and 8% yields, respectively
(Scheme 2). It was revealed that the silyl group was mainly
attached to the ꢀ carbon of the ynamide. The directing effect
of the sulfonyl group of ynamides would play an important
role in determining the regiochemistry of the silylcupration.8
Reaction of N-phenylethynylamides 1b with Me3SiCu pro-
vided the desired product 2b with high regio- and stereoselec-
tivity (Scheme 3). Ynamide having an allyl group 1c under-
went reaction to furnish the silylated product 2c without dif-
ficulty. Silylcupration of 1b with dimethylphenylsilylcopper
(PhMe2SiCu) also proceeded smoothly to afford 2d.
Silylcupration of Ynamides
Vinylsilanes play an important role as synthetic building
blocks because they react with various electrophiles in the
presence or absence of Lewis acid and they are used widely
for palladium-catalyzed cross-coupling reactions.4 Silylmeta-
lation of alkynes is one of the most general methods for syn-
thesis of multi-substituted vinylsilanes.5 We report herein
silylcupration of ynamides with high regio- and stereoselec-
tivity.6
The vinylcopper generated by the silylcupration reacted
with allyl bromide to provide the corresponding product 4 in
high yield (Scheme 4).
Preparation of internal ynamides 1 was performed according
(0.20 mol. amt.)
N
N
CuSO4 5H2O (0.1 mol. amt.)
K2CO3 (2.0 mol. amt.)
SO2Ar
N
R'
SO2Ar
R'
R C C Br + H
R
C C N
toluene, 60 °C
1
Scheme 1.
Me3Si
H+
SiMe3
β
α
β α
α
β
Ts
+
Me C C N
+
Me3Si Cu
(3.0 mol. amt.)
Me
N
Ts
Me
N Ts
THF / HMPA
−60 °C, 2 h
Me
Me
2a
77% (E/Z = 97:3)
Me
3a
8%
1a
Scheme 2.
Published on the web March 13, 2008; doi:10.1246/bcsj.81.373

374 Bull. Chem. Soc. Jpn. Vol. 81, No. 3 (2008)
Copper-Mediated Addition Reactions to Ynamides
Si
H+
Ts
regio- and
+
Ph C C N
+
Si Cu
(3.0 mol. amt.)
stereoisomers
N Ts
Ph
THF / HMPA
−60 °C, 2 h
R
R
R = Me: 1b
R = allyl: 1c
2
2b
Si = SiMe3, R = Me:
89% (92% isomeric purity)
Si = SiMe3, R = allyl: 2c 75% (96% isomeric purity)
Si = SiPhMe2 , R = Me: 2d 81% (93% isomeric purity)
Scheme 3.
Br
Me3Si
Ph
Ts
regio- and
stereoisomers
Ph C C N
+
Me3Si Cu
+
THF / HMPA
−60 °C, 2 h
rt, 2 h
N
Ts
Me (3.0 mol. amt.)
Me
1b
4
95% (92% isomeric purity)
Scheme 4.
O
TiCl4
(2.0 mol. amt.)
PhMe2Si
Ph
O
+
N Ts
Cl
(2.0 mol. amt.)
Ph
N Ts
CH2Cl2
rt, 3 h
Me
Me
2d
5
47%
(96% isomeric purity)
Scheme 5.
BuMgBr (2.0 mol. amt.) BrMg
Bu
Ts
(D)H
Bu
Ts
Ts
•
CuBr Me2S (0.10 mol. amt.)
N
N
)
Ph C C N
H2O (D2O)
Et2O, −78 °C to rt
Ph
Ph
6 6-d
1c
7
(
86% (96%D)
DME/Et2O
reflux (Bath temp. 80 °C)
C
N
Bu
Ph
8a 47%
Scheme 6.
Then, Lewis acid-catalyzed reaction of (E)-ꢀ-silylenamide
with an electrophile was examined. Treatment of (E)-ꢀ-silylen-
amide 2d with acetyl chloride in the presence of titanium tetra-
chloride (TiCl4) in CH2Cl2 at room temperature afforded the
corresponding product 5 in 47% NMR yield with regio- and
stereoselectivity (Scheme 5).
The initial carbomagnesiation proceeded smoothly by using
Grignard reagents and a copper catalyst.10 Treatment of N-
allyl-N-phenylethynyl-p-toluenesulfonamide (1c) with 2.0 mo-
lar amounts of butylmagnesium bromide in the presence of
CuBr Me2S (0.1 mol. amt.) in diethyl ether at ambient temper-
ꢁ
ature afforded 6 in 86% yield after hydrolysis.11 Quenching
the reaction with deuterium oxide provided the corresponding
deuterium-labeled product 6-d (96%D). Hence, it is suggested
that intermediate 7 was formed in the reaction flask. When
organomagnesium 7 was heated in a mixed solvent of 1,2-di-
methoxyethane (DME) and diethyl ether, pentenenitrile 8a
was obtained in 47% yield, along with 34% of 6 (Scheme 6).
There are two possible mechanisms of the formation of
nitrile 8a (Scheme 7). The [3,3] sigmatropic rearrangement of
the organomagnesium 7 and subsequent elimination of magne-
sium sulfinate from 9 would afford 8a (Path A). The other
Carbomagnesiation Reactions of Ynamides Followed
by Aza-Claisen Rearrangement
The [3,3] sigmatropic rearrangement of 3-aza-1,5-hexa-
dienes is called an aza-Claisen rearrangement and plays an
important role in organic synthesis.9 We describe herein carbo-
magnesiation reactions of N-allyl-N-(phenylethynyl)arenesul-
fonamides and the subsequent aza-Claisen rearrangement.
The transformation offers a new protocol to the repertoire of
chemistry towards the synthesis of 4-pentenenitriles.

H. Yasui et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 3 (2008)
375
BrMg
SO2Ar
N
[3,3]
(Path A)
Bu
Ph
elimination
BrMg
Bu
SO2Ar
9
C N
Bu
N
Ph
Ph
Bu
Ph
8a
7
C
N
elimination
(Path B)
[3,3]
10
Scheme 7.
arrangement, 2,2,3,3-tetrasubstituted 4-pentenenitrile 8h was
obtained in the reaction of N-(3-methyl-2-butenyl)amide 1h
(Entry 4). It is difficult to synthesize such a sterically congest-
ed nitrile by conventional nitrile synthesis. The reactions of
N-2-butenyl- and N-cinnamylamides 1i and 1j afforded mix-
tures of diastereomers (Entries 5 and 6). The reactions of 1k
and 1l with butylmagnesium bromide gave the corresponding
nitriles 8k and 8l in lower yields of 33% and 34%, respectively
(Entries 7 and 8). The phenyl group at the acetylenic terminus
proved to be indispensable for the success of the reaction.
A similar reaction of N-allyl-N-1-octynyl-p-toluenesulfon-
amide resulted in formation of a complex mixture containing
6% of the anticipated nitrile and 31% of N-allyl-p-toluene-
sulfonamide. Unfortunately, silylcupration of ynamide 1c fol-
lowed by heating gave no desired aza-Claisen rearrangement
product.
H
Ts
Ts
H
∆
N
N
Bu
Ph
Bu
Ph
toluene, reflux
overnight
6
Scheme 8.
mechanism (Path B) is as follows. First, elimination of magne-
sium sulfinate from organomagnesium 7 could take place to
give ketene imine intermediate 10. Then, [3,3] sigmatropic
rearrangement of 10 could proceed to furnish nitrile 8a. The
[3,3] sigmatropic rearrangement of 3-aza-1,2,5-hexatrienes
has been known to proceed smoothly.12 It is worth noting that
heating 6 in boiling toluene resulted in complete recovery of 6
(Scheme 8).
Table 1 summarizes the results of the synthesis of 4-pentene-
nitriles starting from Grignard reagents and ynamides having
an allyl group on the nitrogen. Primary alkyl Grignard reagents
including a bulky neopentylmagnesium reagent participated
in the reaction. When phenyl and secondary alkyl Grignard
reagents were used, the yields of desired products were
much lower (Entries 4 and 7). Ynamides 1d, having a p-fluoro-
phenylsulfonyl group on the nitrogen, improved the yields
(Entries 5 and 6).
Experimental
General. 1H NMR (500 MHz) and 13C NMR (125.7 MHz)
spectra were taken on a Varian UNITY INOVA 500 spectrometer
1
unless otherwise noted. H NMR and 13C NMR spectra were ob-
tained in CDCl3 with tetramethylsilane as an internal standard.
Chemical shifts (ꢁ) are in parts per million relative to tetramethyl-
silane at 0.00 ppm for 1H and relative to CDCl3 at 77.20 ppm
for 13C unless otherwise noted. IR spectra were determined on a
SHIMADZU FTIR-8200PC spectrometer. Mass spectra were de-
termined on a JEOL Mstation 700 spectrometer. TLC analyses
were performed on commercial glass plates bearing 0.25-mm
layer of Merck Silica gel 60F254. Silica gel (Wakogel 200 mesh)
The scope of substrates was investigated (Table 2). N-(2-
Methyl-2-propenyl)amides 1e and 1f and N-(2-phenyl-2-pro-
penyl)amide 1g participated in the reaction (Entries 1–3).
Due to the inherent regiospecificity of the aza-Claisen re-
Table 1. Carbomagnesiation of Ynamides Followed by Aza-Claisen Rearrangement
SO2Ar
RMgBr
C
N
•
Ph C C N
cat. CuBr Me2S
R
Ph
DME/Et2O (A) or
THF/Et2O (B)
Et2O, −78 °C to rt
1
8
Bath temp. 80 °C
Entry
1
Ar
RMgBr
Solvent
TimeaÞ/h
8
YieldbÞ/%
1
2
3
4
5
6
7
1c
1c
1c
1c
1d
1d
1d
p-Tolyl
p-Tolyl
p-Tolyl
p-Tolyl
p-FC6H4
p-FC6H4
p-FC6H4
BuMgBr
EtMgBr
A
B
B
B
A
B
B
5
4
18
4
4
4
19
8a
8b
8c
8d
8a
8b
8e
47
47
46
27
61
50
23
tBuCH2MgBr
PhMgBr
BuMgBr
EtMgBr
iPrMgBr
a) Time for the rearrangement. b) Isolated yield.

376 Bull. Chem. Soc. Jpn. Vol. 81, No. 3 (2008)
Copper-Mediated Addition Reactions to Ynamides
Table 2. Scope and Limitation of Carbomagnesiation Followed by Aza-Claisen Rear-
rangement
SO2Ar
BuMgBr
C
N
Ar'
C
C N
Bu
Ar'
•
cat. CuBr Me2S
R1
R1
R2
Et2O, −78 °C to rt
DME/Et2O
Bath temp. 80 °C
R3
R2
R3
1
8
SO2Ar
C
N
Bu
Ar'
Ar'
C
C
N
N
R1
R1
Entry
1
8
YieldaÞ/%
R2
R3
R2
R3
SO2Ar
C
N
1
2
1e (Ar = p-tolyl)
8f
48 (from 1e)
58 (from 1f)
Bu
Ph
Ph
Ph
C
C
C
1f (Ar = p-FC6H4)
Ts
C
N
Bu
Ph
C N
3
1g
8g
37
Ph
Ph
Ts
C
C
N
Bu
Ph
Ph
Ph
Ph
C
C
C
C
C
N
4
5
1h
8h
61
57
Ts
Ts
N
Bu
Ph
N
N
1ibÞ
8icÞ
C
N
Bu
Ph
C
6
1j
8jdÞ
49
Ph
Ph
C
C
N
N
Ts
Bu
p-MeOC6H4
p-CF3C6H4
C
C
C N
7
8
1k
1l
8k
8l
33
34
p-MeOC6H4
Ts
Bu
C N
p-CF3C6H4
a) Isolated yield. b) E/Z = 4:1. c) Diastereomer ratio = 1.4:1. d) Diastereomer
ratio = 1.6:1.
was used for column chromatography. The analyses were carried
1b (114 mg, 0.40 mmol) in THF (3 mL) was added. After stirring
at ꢃ60 ꢂC for 2 h, allyl bromide (0.17 mL, 2.0 mmol) was added
and the reaction mixture was stirred at room temperature for
2 h. A saturated aqueous solution of ammonium chloride (2 mL)
was added. The organic compounds were extracted with a mixture
of ethyl acetate and hexane twice. The combined organic portion
was dried over anhydrous sodium sulfate and concentrated in
vacuo. Chromatographic purification on silica gel afforded 2b
(151 mg, 0.38 mmol, 92% isomeric purity) in 95% yield.
out at the Elemental Analysis Center of Kyoto University.
Unless otherwise noted, materials obtained from commercial
suppliers were used without further purification. THF and ether
were purchased from Kanto Chemical Co., stored under nitrogen,
and used as provided. Ynamides 1 were prepared by copper-cata-
lyzed alkynylation of amides.7 Trimethylsilyllithium and dimeth-
ylphenylsilyllithium were prepared by conventional methods.13
Typical Procedure for Silylcupration of Ynamides. A solu-
tion of methyllithium (1.1 mL, 1.1 mol Lꢃ1 diethyl ether solution,
1.2 mmol) was added to hexamethyldisilane (0.37 mL, 1.8 mmol)
in freshly distilled hexamethylphosphoric triamide (1.2 mL) at 0
ꢂC under argon. The mixture was stirred at 0 ꢂC for 15 min. After
THF (3 mL) was added, the reaction mixture was cooled to ꢃ60
Typical Procedure for Carbomagnesiation Reaction of
Ynamides Followed by Aza-Claisen Rearrangement. CuBr
ꢁ
SMe2 (6 mg, 0.03 mmol) and N-allyl-N-phenylethynyl-p-fluoro-
benzenesulfonamide (1d, 95 mg, 0.30 mmol) were placed in a 20-
mL reaction flask under argon. Diethyl ether (3 mL) was added. A
solution of butylmagnesium bromide (0.53 mL, 1.13 mol Lꢃ1 di-
ethyl ether solution, 0.60 mmol) was added at ꢃ78 ꢂC. The mix-
ꢂC. CuBr SMe2 (247 mg, 1.8 mmol) was added and the resulting
ꢁ
mixture was stirred at ꢃ60 ꢂC for 15 min. A solution of ynamide

H. Yasui et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 3 (2008)
377
ture was stirred at room temperature for 1 h. DME (5 mL) was
added, and the reaction mixture was refluxed for 4 h (bath temp,
80 ꢂC). A saturated aqueous solution of ammonium chloride (2
mL) was added. The organic compounds were extracted with a
mixture of ethyl acetate and hexane twice. The combined organic
portion was dried over anhydrous sodium sulfate and concentrated
in vacuo. Chromatographic purification on silica gel afforded 8a
(39 mg, 0.18 mmol) in 61% yield.
J ¼ 1:0 Hz, 3H), 2.44 (s, 3H), 4.05 (d, J ¼ 8:0 Hz, 2H), 5.20
(tsept, J ¼ 8:0, 1.0 Hz, 1H), 7.24–7.35 (m, 7H), 7.81–7.84 (m,
2H); 13C NMR (CDCl3) ꢁ 18.20, 21.81, 25.91, 49.80, 70.68,
83.05, 117.21, 123.26, 127.72, 127.92, 128.39, 129.80, 131.28,
135.07, 139.45, 144.65; HRMS (EI) Found: 339.1293. Calcd for
C20H21NO2S: 339.1293 [Mþ].
N-2-Butenyl-N-phenylethynyl-p-toluenesulfonamide (1i, a 8:2
Mixture of Stereoisomers): IR (neat) 2919, 2234, 1366, 1171,
1091, 937, 756, 582, 546 cmꢃ1; 1H NMR (CDCl3) ꢁ 1.65–1.68 (m,
3H), 2.43 (s, 3H), 3.96–3.98 (m, 2 ꢄ 0.8H), 4.11 (d, J ¼ 6:5 Hz,
2 ꢄ 0.2H), 5.40–5.46 (m, 1H), 5.68–5.75 (m, 1H), 7.23–7.35 (m,
7H), 7.81–7.85 (m, 2H); 13C NMR (CDCl3) (E-isomer) ꢁ 17.80,
21.71, 54.10, 71.04, 82.73, 123.10, 123.74, 127.78, 127.89,
128.34, 129.79, 131.31, 132.28, 134.96, 144.70; HRMS (FAB)
Found: 325.1138. Calcd for C19H19NO2S: 325.1136 [Mþ].
N-Phenylethynyl-N-[(E)-3-phenyl-2-propenyl]-p-toluene-
sulfonamide (1j): IR (neat) 3029, 2235, 1597, 1495, 1363, 1169,
Characterization Data. The 1H and 13C NMR spectral data of
compounds 1c,7 8a,3 and 8d14 can be found in the literature.
N-Methyl-N-1-propynyl-p-toluenesulfonamide (1a):
(nujol) 2924, 2855, 2265, 1456, 1355, 1168, 1158, 1042, 816,
677, 566, 545 cmꢃ1
IR
;
1H NMR (CDCl3) ꢁ 1.88 (s, 3H), 2.46 (s,
3H), 3.01 (s, 3H), 7.34–7.39 (m, 2H), 7.76–7.81 (m, 2H); 13C NMR
(CDCl3) ꢁ 3.39, 21.83, 39.43, 64.26, 73.90, 127.97, 129.87,
133.49, 144.64; Found: C, 59.16; H, 5.82%. Calcd for C11H13-
NO2S: C, 59.17; H, 5.87%; Mp 99–100 ꢂC.
1
N-Methyl-N-phenylethynyl-p-toluenesulfonamide (1b): IR
1090, 753, 692, 586 cmꢃ1; H NMR (CDCl3) ꢁ 2.38 (s, 3H), 4.21
(nujol) 2924, 2233, 1595, 1365, 1164, 764, 676, 546 cmꢃ1
;
(dd, J ¼ 7:0, 1.5 Hz, 2H), 6.07 (dt, J ¼ 16:0, 7.0 Hz, 1H), 6.55 (d,
J ¼ 16:0 Hz, 1H), 7.20–7.33 (m, 12H), 7.84–7.86 (m, 2H);
13C NMR (CDCl3) ꢁ 21.68, 54.34, 71.16, 82.66, 121.84, 122.86,
126.69, 127.84, 127.92, 128.20, 128.33, 128.65, 129.86, 131.37,
134.83, 135.34, 136.09, 144.85; HRMS (EI) Found: 387.1291.
Calcd for C24H21NO2S: 387.1293 [Mþ].
1H NMR (CDCl3) ꢁ 2.46 (s, 3H), 3.15 (s, 3H), 7.27–7.31 (m, 3H),
7.34–7.38 (m, 4H), 7.83–7.85 (m, 2H); 13C NMR (CDCl3) ꢁ
21.85, 39.49, 69.19, 84.11, 122.87, 128.02, 128.04, 128.44, 129.98,
131.57, 133.40, 144.97; Found: C, 67.07; H, 5.25%. Calcd for
C16H15NO2S: C, 67.34; H, 5.30%; Mp 85–86 ꢂC.
N-Phenylethynyl-N-2-propenyl-p-fluorobenzenesulfonamide
N-p-Methoxyphenylethynyl-N-2-propenyl-p-toluenesulfon-
amide (1k): IR (neat) 2935, 2839, 2237, 1606, 1512, 1363, 1250,
(1d): IR (nujol) 2925, 2855, 2235, 1492, 1367, 1181, 545 cmꢃ1
;
1H NMR (CDCl3) ꢁ 4.08 (dt, J ¼ 6:5, 1.0 Hz, 2H), 5.24–5.33 (m,
2H), 5.79 (ddt, J ¼ 16:5, 10.0, 6.5 Hz, 1H), 7.23–7.30 (m, 5H),
7.34–7.36 (m, 2H), 7.97–8.00 (m, 2H); 13C NMR (CDCl3) ꢁ
54.67, 71.30, 81.99, 116.66 (d, J ¼ 22:4 Hz), 120.51, 122.68,
128.19, 128.48, 130.74, 130.82, 131.61, 133.85, 165.93 (d, J ¼
254:8 Hz). Found: C, 64.97; H, 4.70%. Calcd for C17H14NO2FS:
C, 64.75; H, 4.47%; Mp 77.7–79.6 ꢂC.
1171, 664 cmꢃ1; H NMR (CDCl3) ꢁ 2.46 (s, 3H), 3.81 (s, 3H),
1
4.04 (dt, J ¼ 6:5, 1.5 Hz, 2H), 5.20–5.24 (m, 1H), 5.24–5.32 (m,
1H), 5.79 (ddt, J ¼ 17:0, 10.0, 6.5 Hz, 1H), 6.80–6.85 (m, 2H),
7.28–7.34 (m, 2H), 7.34–7.39 (m, 2H), 7.82–7.87 (m, 2H);
13C NMR (CDCl3) ꢁ 21.76, 54.56, 55.40, 70.61, 80.94, 114.00,
114.80, 120.05, 127.90, 129.84, 131.11, 133.47, 134.80, 144.85,
159.61; HRMS (FAB) Found: 341.1082. Calcd for C19H19NO3S:
341.1086 [Mþ].
N-2-Propenyl-N-[p-(trifluoromethyl)phenylethynyl]-p-tolu-
enesulfonamide (1l): IR (neat) 2929, 2235, 1615, 1370, 1323,
1171, 1126, 1105, 1066, 842, 664 cmꢃ1; 1H NMR (CDCl3) ꢁ 2.47
(s, 3H), 4.08 (dt, J ¼ 6:5, 1.5 Hz, 2H), 5.26–5.34 (m, 2H), 5.80
(ddt, J ¼ 17:0, 10.0, 6.5 Hz, 1H), 7.38 (d, J ¼ 8:5 Hz, 2H), 7.43
(d, J ¼ 8:5 Hz, 2H), 7.54 (d, J ¼ 8:0 Hz, 2H), 7.84–7.86 (m, 2H);
13C NMR (CDCl3) ꢁ 21.89, 54.53, 70.61, 85.19, 120.55, 124.21
(q, J ¼ 270:7 Hz), 125.41 (q, J ¼ 3:9 Hz), 127.13, 128.01, 129.47
(q, J ¼ 32:5 Hz), 130.11, 130.97, 131.21, 134.91, 145.22; HRMS
(FAB) Found: 380.0936. Calcd for C19H17NO2F3S: 380.0932
[MHþ].
N-Methyl-N-[(E)-2-(trimethylsilyl)propenyl]-p-toluenesulfon-
amide (2a): IR (neat) 2955, 1614, 1349, 1250, 1166, 839, 713
cmꢃ1 1H NMR (CDCl3): ꢁ 0.07 (s, 9H), 1.77 (s, 3H), 2.43 (s,
;
3H), 2.80 (s, 3H), 5.88 (s, 1H), 7.31 (d, J ¼ 8:0 Hz, 2H), 7.64 (d,
J ¼ 8:0 Hz, 2H); 13C NMR (CDCl3) ꢁ ꢃ2:04, 14.86, 21.69, 37.57,
127.31, 127.77, 129.56, 129.66, 132.41, 143.64; Found: C, 56.69,
7.80%. Calcd for C14H23NO2SiS: C, 56.52; H, 7.79%.
N-Methyl-N-[(E)-2-phenyl-2-(trimethylsilyl)ethenyl]-p-tolu-
enesulfonamide (2b): IR (neat) 2955, 1607, 1353, 1248, 1169,
;
838, 758, 698 cmꢃ1 1H NMR (CDCl3) ꢁ 0.06 (s, 9H), 2.42 (s,
3H), 2.47 (s, 3H), 6.69–6.71 (m, 2H), 6.73 (s, 1H), 7.09–7.16 (m,
3H), 7.35 (d, J ¼ 8:0 Hz, 2H), 7.66 (d, J ¼ 8:0 Hz, 2H); 13C NMR
(CDCl3) ꢁ ꢃ1:20, 21.77, 35.76, 125.96, 126.67, 127.23, 127.97,
128.52, 129.90, 131.48, 135.24, 140.00, 143.87; Found: C, 63.37;
H, 6.93%. Calcd for C19H25NO2SiS: C, 63.47; H, 7.01%.
N-(2-Methyl-2-propenyl)-N-phenylethynyl-p-toluenesulfon-
amide (1e): IR (neat) 2976, 2920, 2235, 1597, 1366, 1169, 756,
;
691, 589 cmꢃ1 1H NMR (CDCl3) ꢁ 1.75 (s, 3H), 2.43 (s, 3H),
3.94 (s, 2H), 4.97 (s, 2H), 7.25–7.27 (m, 3H), 7.32–7.35 (m, 4H),
7.84 (d, J ¼ 8:5 Hz, 2H); 13C NMR (CDCl3) ꢁ 19.82, 21.74,
58.05, 70.85, 82.43, 115.98, 122.95, 127.79, 127.81, 128.32,
129.86, 131.32, 134.60, 138.80, 144.81. Found: C, 69.96; H,
6.07%. Calcd for C19H19NO2S: C, 70.13; H, 5.88%.
N-(2-Methyl-2-propenyl)-N-phenylethynyl-p-fluorobenzene-
sulfonamide (1f): IR (neat) 3081, 2237, 1592, 1495, 1368, 1175,
1
1156, 837, 756, 589 cmꢃ1; H NMR (CDCl3) ꢁ 1.76 (s, 3H), 3.98
(s, 2H), 4.98 (s, 1H), 4.99 (s, 1H), 7.23–7.34 (m, 7H), 7.97–8.00
(m, 2H); 13C NMR (CDCl3) ꢁ 19.91, 58.26, 71.13, 82.05, 116.28,
116.63 (d, J ¼ 22:5 Hz), 122.76, 128.10, 128.46, 128.60, 130.71
(d, J ¼ 9:6 Hz), 131.53, 138.68, 165.89 (d, J ¼ 255:3 Hz); HRMS
(FAB) Found: 330.0958. Calcd for C18H17NO2FS: 330.0964
[MHþ].
N-Phenylethynyl-N-(2-phenyl-2-propenyl)-p-toluenesulfon-
amide (1g): IR (nujol) 2924, 2854, 2248, 1362, 1174, 915, 758,
608, 550 cmꢃ1
;
1H NMR (CDCl3) ꢁ 2.43 (s, 3H), 4.43 (s, 2H),
5.33 (s, 1H), 5.53 (s, 1H), 7.24–7.33 (m, 10H), 7.40–7.41 (m, 2H),
7.78 (d, J ¼ 8:5 Hz, 2H); 13C NMR (CDCl3) ꢁ 21.81, 55.50,
71.43, 82.29, 117.94, 122.95, 126.52, 127.84, 127.93, 128.23,
128.33, 128.56, 129.87, 131.40, 134.40, 138.16, 141.44, 144.83.
Found: C, 74.33; H, 5.43%. Calcd for C24H21NO2S: C, 74.39%;
H, 5.46%. Mp 100.7–101.0 ꢂC.
N-(3-Methyl-2-butenyl)-N-phenylethynyl-p-toluenesulfon-
amide (1h): IR (neat) 2360, 2235, 1363, 1169, 1091, 754, 691,
N-[(E)-2-Phenyl-2-(trimethylsilyl)ethenyl]-N-2-propenyl-p-
toluenesulfonamide (2c): IR (neat) 2956, 1605, 1353, 1249,
1
584 cmꢃ1; H NMR (CDCl3) ꢁ 1.68 (d, J ¼ 1:0 Hz, 3H), 1.70 (d,

378 Bull. Chem. Soc. Jpn. Vol. 81, No. 3 (2008)
Copper-Mediated Addition Reactions to Ynamides
1167, 1092, 837, 770 cmꢃ1; 1H NMR (CDCl3) ꢁ 0.06 (s, 9H), 2.46
(s, 3H), 3.53–3.55 (m, 2H), 4.77–4.81 (m, 1H), 4.91–4.93 (m, 1H),
5.29 (ddt, J ¼ 17:0, 10.5, 6.0 Hz, 1H), 6.54 (s, 1H), 6.71–6.73 (m,
2H), 7.12–7.18 (m, 3H), 7.33 (d, J ¼ 8:5 Hz, 2H), 7.68 (d, J ¼
8:5 Hz, 2H); 13C NMR (CDCl3) ꢁ ꢃ1:20, 21.73, 49.58, 117.29,
126.21, 127.32, 127.93, 128.23, 129.54, 129.80, 131.30, 132.80,
136.71, 139.73, 143.76; Found: C, 65.50; H, 7.00%. Calcd for
C21H27NO2SiS: C, 65.41; H, 7.06%.
ꢁ 0.92 (t, J ¼ 7:5 Hz, 3H), 1.94 (dq, J ¼ 14:5, 7.5 Hz, 1H), 2.08
(dq, J ¼ 14:5, 7.5 Hz, 1H), 2.67–2.69 (m, 2H), 5.10–5.15 (m,
2H), 5.65 (ddt, J ¼ 17:5, 10.5, 7.0 Hz, 1H), 7.29–7.33 (m, 1H),
7.37–7.41 (m, 4H); 13C NMR (CDCl3) ꢁ 9.75, 33.26, 45.17, 48.97,
120.04, 122.15, 126.35, 127.90, 128.99, 132.08, 137.96. Found: C,
84.17; H, 8.37%. Calcd for C13H15N: C, 84.28; H, 8.16%.
2-Neopentyl-2-phenyl-4-pentenenitrile (8c): IR (neat) 2956,
1
2909, 2236, 1642, 1601, 1449, 924, 702 cmꢃ1; H NMR (CDCl3)
N-[(E)-2-Dimethylphenylsilyl-2-phenylethenyl]-N-methyl-p-
toluenesulfonamide (2d): IR (neat) 2957, 1594, 1354, 1248,
ꢁ 0.82 (s, 9H), 1.98 (d, J ¼ 14:5 Hz, 1H), 2.06 (d, J ¼ 14:5 Hz,
1H), 2.67 (d, J ¼ 7:0 Hz, 2H), 5.09–5.14 (m, 2H), 5.56–5.64 (m,
1H), 7.29–7.32 (m, 1H), 7.36–7.40 (m, 2H), 7.46–7.48 (m, 2H);
13C NMR (CDCl3) ꢁ 31.03, 32.18, 45.97, 48.95, 52.37, 120.25,
122.78, 126.61, 127.80, 128.82, 131.83, 138.58. Found: C, 84.24;
H, 9.26%. Calcd for C16H21N: C, 84.53; H, 9.31%.
1
1168, 936, 810, 754, 702 cmꢃ1; H NMR (CDCl3) ꢁ 0.32 (s, 6H),
2.43 (s, 3H), 2.47 (s, 3H), 6.67–6.69 (m, 2H), 6.75 (s, 1H), 7.10–
7.12 (m, 3H), 7.34 (d, J ¼ 8:0 Hz, 2H), 7.38–7.44 (m, 3H), 7.51–
7.52 (m, 2H), 7.59 (d, J ¼ 8:0 Hz, 2H); 13C NMR (CDCl3) ꢁ
ꢃ2:82, 21.69, 35.67, 124.36, 126.01, 127.14, 127.86, 127.89,
128.65, 129.32, 129.83, 133.34, 134.22, 134.99, 137.59, 139.49,
143.84; Found: C, 67.97; H, 6.49%. Calcd for C24H27NO2SiS:
C, 68.37; H, 6.45%.
2-Isopropyl-2-phenyl-4-pentenenitrile (8e): IR (neat) 2967,
1
2235, 1495, 1449, 923, 761, 699 cmꢃ1; H NMR (CDCl3) ꢁ 0.81
(d, J ¼ 6:5 Hz, 3H), 1.21 (d, J ¼ 6:5 Hz, 3H), 2.18 (sept, J ¼
6:5 Hz, 1H), 2.65 (ddt, J ¼ 14:0, 7.0, 1.0 Hz, 1H), 2.86 (ddt,
J ¼ 14:0, 7.5, 1.0 Hz, 1H), 5.01–5.04 (m, 1H), 5.06–5.10 (m, 1H),
5.43–5.51 (m, 1H), 7.28–7.31 (m, 1H), 7.36–7.38 (m, 4H);
13C NMR (CDCl3) ꢁ 18.70, 18.95, 37.24, 42.26, 53.89, 119.62,
121.07, 126.89, 127.78, 128.80, 132.39, 137.74. Found: C, 84.53;
H, 8.67%. Calcd for C14H17N: C, 84.37; H, 8.60%.
N-Methyl-N-{(E)-1-[ꢀ-(trimethylsilyl)benzylidene]-3-buten-
yl}-p-toluenesulfonamide (4): IR (neat) 2954, 1600, 1344, 1251,
1
1151, 840, 718, 701 cmꢃ1; H NMR (CDCl3) ꢁ 0.13 (s, 9H), 2.39
(s, 3H), 2.57 (s, 3H), 3.38 (d, J ¼ 6:5 Hz, 2H), 4.93–4.96 (m, 1H),
4.99–5.02 (m, 1H), 5.76 (ddt, J ¼ 17:0, 10.5, 6.5 Hz, 1H), 7.01
(br, 2H), 7.18–7.19 (m, 3H), 7.24–7.28 (m, 2H), 7.47 (d, J ¼
8:5 Hz, 2H); 13C NMR (CDCl3) ꢁ 0.43, 21.51, 38.77, 40.35,
117.60, 125.68, 127.51, 127.90 (br, 2C), 129.36, 135.09, 137.45,
141.90, 142.92, 143.98, 146.09; Found: C, 65.85; H, 7.37%. Calcd
for C22H29NO2SiS: C, 66.12; H, 7.31%.
N-Methyl-N-[(E)-3-oxo-2-phenyl-1-butenyl]-p-toluenesulfon-
amide (5): IR (nujol) 2924, 2854, 1657, 1613, 1357, 1347, 1292,
1169, 1155, 971, 754, 724, 702, 664 cmꢃ1 1H NMR (CDCl3) ꢁ
;
2.16 (s, 3H), 2.46 (s, 6H), 7.00–7.02 (m, 2H), 7.27–7.29 (m,
3H), 7.37 (d, J ¼ 8:0 Hz, 2H), 7.71–7.73 (m, 2H), 8.10 (s, 1H);
13C NMR (CDCl3) ꢁ 21.83, 28.00, 35.14, 123.49, 127.43, 128.12,
128.34, 130.34, 131.01, 134.55, 135.29, 138.07, 144.99, 197.89;
HRMS (EI) Found: 329.1085. Calcd for C18H19NO3S: 329.1086
[Mþ].
2-Butyl-4-methyl-2-phenyl-4-pentenenitrile (8f): IR (neat)
3078, 2958, 2864, 2236, 1647, 1495, 1449, 900, 699 cmꢃ1
;
1H NMR (CDCl3) ꢁ 0.85 (t, J ¼ 7:5 Hz, 3H), 1.05–1.12 (m, 1H),
1.24–1.34 (m, 2H), 1.41–1.49 (m, 1H), 1.53 (s, 3H), 1.92 (dt, J ¼
13:5, 4.5 Hz, 1H), 2.01 (dt, J ¼ 12:5, 4.5 Hz, 1H), 2.60 (d, J ¼
14:0 Hz, 1H), 2.70 (d, J ¼ 14:0 Hz, 1H), 4.71 (s, 1H), 4.83 (s,
1H), 7.26–7.31 (m, 1H), 7.36–7.42 (m, 4H); 13C NMR (CDCl3) ꢁ
13.98, 22.74, 23.83, 27.42, 41.06, 47.81, 49.17, 116.65, 122.75,
126.31, 127.79, 128.89, 138.51, 140.17. Found: C, 84.76; H,
9.46%. Calcd for C16H21N: C, 84.53; H, 9.31%.
2-Butyl-2,4-diphenyl-4-pentenenitrile (8g): IR (neat) 2958,
2933, 2236, 1686, 1627, 1600, 1495, 1448, 907, 778, 698 cmꢃ1
;
1H NMR (CDCl3) ꢁ 0.79 (t, J ¼ 7:5 Hz, 3H), 1.01–1.42 (m, 4H),
1.87 (dt, J ¼ 13:5, 4.5 Hz, 1H), 1.95 (dt, J ¼ 12:0, 4.5 Hz, 1H),
3.07 (d, J ¼ 13:5 Hz, 1H), 3.16 (d, J ¼ 13:5 Hz, 1H), 5.09 (s, 1H),
5.28 (s, 1H), 7.15–7.33 (m, 10H); 13C NMR (CDCl3) ꢁ 13.88,
22.67, 27.42, 40.22, 46.50, 48.64, 118.84, 122.18, 126.38, 126.67,
127.53, 127.66, 128.26, 128.68, 138.12, 141.81, 143.72; HRMS
(FAB) Found: 290.1901. Calcd for C21H24N: 290.1908 [MHþ].
N-[(Z)-2-Phenyl-1-hexenyl]-N-2-propenyl-p-toluenesulfon-
amide (6): IR (nujol) 2924, 2855, 1347, 1159, 934, 770, 664
cmꢃ1
;
1H NMR (CDCl3) ꢁ 0.84 (t, J ¼ 7:5 Hz, 3H), 1.21–1.30
(m, 4H), 2.33 (m, 2H), 2.45 (s, 3H), 3.51 (dt, J ¼ 6:5, 1.5 Hz,
2H), 4.84–4.88 (m, 1H), 4.95–4.98 (m, 1H), 5.41 (ddt, J ¼ 17:0,
10.5, 6.5 Hz, 1H), 5.88 (s, 1H), 6.97–6.98 (m, 2H), 7.21–7.24 (m,
3H), 7.32 (d, J ¼ 8:0 Hz, 2H), 7.67 (d, J ¼ 8:0 Hz, 2H); 13C NMR
(CDCl3) ꢁ 13.93, 21.72, 22.09, 30.18, 36.25, 52.08, 118.22,
121.06, 127.46, 127.64, 128.13, 128.22, 129.72, 133.13, 136.09,
138.45, 140.79, 143.58. Found: C, 71.57; H, 7.36%. Calcd for
C22H27NO2S: C, 71.51; H, 7.36%. Mp 81.2–81.7 ꢂC.
2-Butyl-3,3-dimethyl-2-phenyl-4-pentenenitrile (8h):
IR
;
(neat) 2961, 2934, 2874, 2233, 1469, 1448, 922, 750, 703 cmꢃ1
1H NMR (CDCl3) ꢁ 0.84 (t, J ¼ 7:5 Hz, 3H), 1.02 (s, 3H), 1.17 (s,
3H), 1.27–1.39 (m, 4H), 1.94–2.00 (m, 1H), 2.05–2.12 (m, 1H),
5.02 (d, J ¼ 18:0 Hz, 1H), 5.15 (d, J ¼ 10:5 Hz, 1H), 5.89 (dd,
J ¼ 18:0, 10.5 Hz, 1H), 7.29–7.39 (m, 5H); 13C NMR (CDCl3) ꢁ
14.03, 23.03, 23.14, 24.48, 28.03, 32.39, 43.23, 56.06, 115.13,
122.71, 127.81, 127.96, 128.77, 134.95, 142.87. Found: C, 84.49;
H, 9.76%. Calcd for C17H23N: C, 84.59; H, 9.60%.
N-[(Z)-1-Deuterio-2-phenyl-1-hexenyl]-N-2-propenyl-p-tolu-
enesulfonamide (6-d): IR (nujol) 2925, 2855, 1340, 1158, 935,
822, 771, 703 cmꢃ1; 1H NMR (CDCl3) ꢁ 0.84 (t, J ¼ 7:5 Hz, 3H),
1.21–1.30 (m, 4H), 2.33 (t, J ¼ 7:5 Hz, 2H), 2.45 (s, 3H), 3.51 (dt,
J ¼ 6:5, 1.0 Hz, 2H), 4.84–4.88 (m, 1H), 4.95–4.98 (m, 1H), 5.41
(ddt, J ¼ 17:0, 10.0, 6.5 Hz, 1H), 6.95–6.97 (m, 2H), 7.21–7.23
(m, 3H), 7.32 (d, J ¼ 8:0 Hz, 2H), 7.67 (d, J ¼ 8:0 Hz, 2H);
13C NMR (CDCl3) ꢁ 13.94, 21.73, 22.09, 30.19, 36.22, 52.01,
118.20, 120.75 (t, J ¼ 26:3 Hz), 127.46, 127.63, 128.13, 128.23,
129.73, 133.16, 136.16, 138.46, 140.46, 143.58. Found: C, 71.58;
H þ D, 7.58%. Calcd for C22H26DNO2S: C, 71.31; H þ D, 7.61%.
Mp 81.1–82.3 ꢂC.
2-Butyl-3-methyl-2-phenyl-4-pentenenitrile (8i, a 59:41 Mix-
ture of Diastereomers): IR (neat) 2959, 2933, 2865, 2235, 1714,
1601, 1495, 1449, 923, 762, 701 cmꢃ1; 1H NMR (CDCl3) ꢁ 0.78–
1.52 (m, 4H), 0.80 (t, J ¼ 7:5 Hz, 3 ꢄ 0.59H), 0.84 (t, J ¼ 7:5 Hz,
3 ꢄ 0.41H), 0.87 (d, J ¼ 6:5 Hz, 3 ꢄ 0.59H), 1.21 (d, J ¼ 7:0
Hz, 3 ꢄ 0.41H), 1.71–1.82 (m, 1 ꢄ 0.59H), 1.90–1.99 (m, 1 ꢄ
0.41H), 1.99–2.12 (m, 1H), 2.52–2.60 (m, 1 ꢄ 0.59H), 2.62–
2.72 (m, 1 ꢄ 0.41H), 4.88–5.00 (m, 2 ꢄ 0.41H), 5.18–5.26 (m,
2 ꢄ 0.59H), 5.50 (ddd, J ¼ 17:0, 10.0, 8.0 Hz, 1 ꢄ 0.41H), 5.88–
5.98 (m, 1 ꢄ 0.59H), 7.20–7.39 (m, 5H); 13C NMR (CDCl3) ꢁ
13.93, 13.96, 16.37, 17.23, 22.70, 22.82, 27.59, 27.61, 37.14,
2-Ethyl-2-phenyl-4-pentenenitrile (8b):
2938, 2236, 1495, 1449, 925, 762, 699 cmꢃ1
IR (neat) 2973,
;
1H NMR (CDCl3)

H. Yasui et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 3 (2008)
379
38.87, 47.10, 48.51, 52.51, 52.62, 117.12, 117.61, 121.26, 121.97,
126.52, 127.10, 127.71, 127.74, 128.60, 128.94, 137.03, 137.93,
138.09, 139.18. Found: C, 84.65; H, 9.55%. Calcd for C16H21N:
C, 84.53; H, 9.31%.
References
Reviews on the chemistry of ynamides: a) C. A. Zificsak,
J. A. Mulder, R. P. Hsung, C. Rameshkumar, L.-L. Wei, Tetra-
hedron 2001, 57, 7575. b) J. A. Mulder, K. C. M. Kurtz, R. P.
Hsung, Synlett 2003, 1379.
1
2-Butyl-2,3-diphenyl-4-pentenenitrile (8j, a 60:40 Mixture
of Diastereomers): IR (CDCl3) 2958, 2932, 2865, 2234, 1602,
1494, 1449, 925, 724, 700 cmꢃ1; 1H NMR (CDCl3) ꢁ 0.75 (t, J ¼
7:0 Hz, 3 ꢄ 0.60H), 0.84 (t, J ¼ 7:0 Hz, 3 ꢄ 0.40H), 0.86–1.06
(m, 1H), 1.09–1.47 (m, 3H), 1.68 (ddd, J ¼ 13:5, 12.0, 4.5 Hz,
1 ꢄ 0.60H), 1.89 (ddd, J ¼ 14:0, 12.5, 4.5 Hz, 1 ꢄ 0.60H), 1.96
(ddd, J ¼ 14:0, 12.5, 4.5 Hz, 1 ꢄ 0.40H), 2.24 (ddd, J ¼ 12:5,
12.5, 4.5 Hz, 1 ꢄ 0.40H), 3.54 (d, J ¼ 9:5 Hz, 1 ꢄ 0.40H), 3.64
(d, J ¼ 8:5 Hz, 1 ꢄ 0.60H), 4.77–4.81 (m, 1 ꢄ 0.60H), 4.98–
5.01 (m, 1 ꢄ 0.60H), 5.26–5.32 (m, 2 ꢄ 0.40H), 6.05 (ddd, J ¼
17:0, 10.5, 8.5 Hz, 1 ꢄ 0.60H), 6.41 (ddd, J ¼ 16:5, 10.0, 9.5
Hz, 1 ꢄ 0.40H), 6.90–6.95 (m, 2 ꢄ 0.40H), 7.06–7.10 (m, 2 ꢄ
0.60H), 7.12–7.24 (m, 2H), 7.28–7.42 (m, 6H); 13C NMR (CDCl3)
ꢁ 14.01, 14.08, 22.77, 22.88, 27.60, 27.68, 37.92, 38.53, 52.99,
53.13, 60.14, 60.84, 118.96, 119.26, 121.85, 121.88, 127.08,
127.21, 127.23, 127.71, 127.89, 127.99, 128.19, 128.59, 128.74,
128.79, 128.83, 129.45, 135.94, 136.71, 136.78, 137.46, 139.06,
139.23. Found: C, 86.95; H, 8.27%. Calcd for C21H23N: C, 87.15;
H, 8.01%.
2
Bergstraßer, Tetrahedron 2000, 56, 8473. b) Silylstannylation
a) Hydroboration: B. Witulski, N. Buschmann, U.
¨
and bisstannylation: S. Miniere, J.-C. Cintrat, Synthesis 2001,
`
705. c) Carbometalation: H. Chechik-Lankin, S. Livshin, I.
Marek, Synlett 2005, 2098. d) Hydrostannylation: D.
Buissonneaud, J.-C. Cintrat, Tetrahedron Lett. 2006, 47, 3139.
3
A part of this work has been communicated: H. Yasui, H.
Yorimitsu, K. Oshima, Chem. Lett. 2007, 36, 32.
A review on the chemistry of vinylsilanes: a) T. H. Chan,
4
I. Fleming, Synthesis 1979, 761. A review on Hiyama cross-
coupling, see: b) Y. Hatanaka, T. Hiyama, Synlett 1991, 845.
5
For examples on silylmetalation of alkynes, see: a) I.
Fleming, T. W. Newton, F. Roessler, J. Chem. Soc., Perkin Trans.
1 1981, 2527. b) H. Hayami, M. Sato, S. Kanemoto, Y. Morizawa,
K. Oshima, H. Nozaki, J. Am. Chem. Soc. 1983, 105, 4491. c) Y.
Okuda, K. Wakamatsu, W. Tuckmantel, K. Oshima, H. Nozaki,
¨
Tetrahedron Lett. 1985, 26, 4629. d) K. Wakamatsu, T. Nonaka,
Y. Okuda, W. Tuckmantel, K. Oshima, K. Utimoto, H. Nozaki,
¨
Tetrahedron 1986, 42, 4427. e) S. Nakamura, M. Uchiyama, T.
Ohwada, J. Am. Chem. Soc. 2004, 126, 11146.
2-Butyl-2-p-methoxylphenyl-4-pentenenitrile (8k): IR (neat)
2937, 2863, 2235, 1611, 1514, 1253, 1185, 1036, 830 cmꢃ1
;
1H NMR (CDCl3) ꢁ 0.85 (t, J ¼ 7:0 Hz, 3H), 1.07–1.16 (m, 1H),
1.21–1.46 (m, 3H), 1.84 (dt, J ¼ 13:5, 4.5 Hz, 1H), 1.97 (dt, J ¼
12:5, 4.5 Hz, 1H), 2.59–2.68 (m, 2H), 3.82 (s, 3H), 5.099–5.104
(m, 1H), 5.12–5.14 (m, 1H), 5.60–5.69 (m, 1H), 6.89–6.92
(m, 2H), 7.28–7.32 (m, 2H); 13C NMR (CDCl3) ꢁ 13.97, 22.72,
27.44, 39.97, 45.63, 47.47, 55.45, 114.26, 119.91, 122.60, 127.37,
130.34, 132.22, 159.08. Found: C, 78.72; H, 8.59%. Calcd for
C16H21NO: C, 78.97; H, 8.70%.
6
Silylcupration of ynamines: L. Capella, A. Capperucci,
G. Curotto, D. Lazzari, P. Dembech, G. Reginato, A. Ricci, Tetra-
hedron Lett. 1993, 34, 3311.
7
Y. Zhang, R. P. Hsung, M. R. Tracey, K. C. M. Kurtz, E. L.
Vera, Org. Lett. 2004, 6, 1151.
A similar directing effect was reported in carbocupration
reactions of ynamides. See Ref. 2c.
a) G. B. Bennett, Synthesis 1977, 589. b) S. Jolidon, H.-J.
8
9
2-Butyl-2-p-(trifluoromethyl)phenyl-4-pentenenitrile (8l):
IR (neat) 2962, 2936, 2866, 2238, 1620, 1329, 1169, 1122, 1071,
Hansen, Helv. Chim. Acta 1977, 60, 978. c) R. P. Lutz, Chem. Rev.
1984, 84, 205. d) S. Blechert, Synthesis 1989, 71. e) A. M. M.
Castro, Chem. Rev. 2004, 104, 2939.
1018, 927, 839 cmꢃ1
;
1H NMR (CDCl3) ꢁ 0.85 (t, J ¼ 7:5 Hz,
3H), 1.03–1.12 (m, 1H), 1.22–1.38 (m, 2H), 1.41–1.49 (m, 1H),
1.90 (dt, J ¼ 13:5, 4.5 Hz, 1H), 2.03 (dt, J ¼ 12:0, 4.5 Hz, 1H),
2.63–2.74 (m, 2H), 5.10–5.14 (m, 2H), 5.58–5.66 (m, 1H), 7.53 (d,
J ¼ 8:5 Hz, 2H), 7.65 (d, J ¼ 8:5 Hz, 2H); 13C NMR (CDCl3) ꢁ
13.86, 22.64, 27.40, 39.79, 45.37, 48.30, 120.65, 121.64, 124.02
(q, J ¼ 270:6 Hz), 126.03 (m), 126.81, 130.0 (q, J ¼ 32:6 Hz),
131.36, 142.40. Found: C, 68.37; H, 6.45%. Calcd for C16H18NF3:
C, 68.31; H, 6.45%.
10 Carbometalation of ynamides was reported. See Ref. 2c.
11 The syn mode in the addition was determined according to
the literature. See Ref. 2c.
12 a) K. C. Brannock, R. D. Burpitt, J. Org. Chem. 1965, 30,
2564. b) M. A. Walters, J. Org. Chem. 1996, 61, 978.
13 a) R. D. Singer, in Science of Synthesis, Organometallics,
ed. by I. Fleming, Thieme, 2002, p. 237. For preparation of
Me3SiLi, see: b) W. C. Still, J. Org. Chem. 1976, 41, 3063. For
preparation of PhMe2SiLi, see: c) H. Gilman, G. D. Lichtenwalter,
J. Am. Chem. Soc. 1958, 80, 607. d) I. Fleming, R. S. Roberts,
S. C. Smith, J. Chem. Soc., Perkin Trans. 1 1998, 1209.
14 C. F. Bender, R. A. Widenhoefer, J. Am. Chem. Soc. 2005,
127, 1070.
This work was supported by Grants-in-Aid for Scientific
Research and COE Research from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.