Regio- and stereoselective multicomponent coupling reaction of alkynes and dimethylzinc involving allylnickelacycles

Article abstract of DOI:10.1055/s-0031-1290764

Nickel catalyzes the multicomponent coupling reaction of vinyl epoxides, alkynes, and dimethylzinc to provide hepta-2,5-dienyl alcohols as a mixture of E- and Z-isomers in high yields. Vinylcyclopropane participates in a similar multicomponent coupling reaction to afford dimethyl α-(hepta-2,5-dienyl) malonates with excellent E-stereoselectivity. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1290764

PRACTICAL SYNTHETIC PROCEDURES
▌2333
pRraectigcailosy-ntahenticdprSoctedeurrees oselective Multicomponent Coupling Reaction of Alkynes and
Dimethylzinc Involving Allylnickelacycles
Nickel-Catalyzed MCRs
Takamichi Mori, Toshiyuki Nakamura, Gen Onodera, Masanari Kimura*
PSP
Graduate School of Engineering, Nagasaki University, 1-14 Bunkyo, Nagasaki 852-8521, Japan
Fax +81(95)8192677; E-mail: masanari@nagasaki-u.ac.jp
Received: 10.02.2012; Accepted: 17.02.2012
No227
Abstract: Nickel catalyzes the multicomponent coupling reaction of vinyl epoxides, alkynes, and dimethylzinc to provide hepta-2,5-dienyl
alcohols as a mixture of E- and Z-isomers in high yields. Vinylcyclopropane participates in a similar multicomponent coupling reaction to
afford dimethyl α-(hepta-2,5-dienyl)malonates with excellent E-stereoselectivity.
Key words: nickel, multicomponent coupling, alkyne, dimethylzinc, vinyl epoxide, cyclopropane
procedure 1
Ni(acac)2 catalyst
R1
R2
OH
+
+
Me2Zn
R2
O
THF, r.t.
R1
E/Z mixture
1
procedure 2
E
Ni(acac)2 catalyst
THF, r.t.
+
R1
R2
+
Me2Zn
R2
E
E
E
R1
3
E = CO2Me
E-selective
Scheme 1 Typical procedure for the three-component coupling reaction of alkyne, dimethylzinc, and vinyl epoxide/vinylcyclopropane
tion with dimethylzinc, butadiene, and carbonyls to
provide homoallylic alcohols and homoallylamines in
Introduction
Multicomponent coupling reactions are among the most high regio- and stereoselectivities (Scheme 3).5
efficient and straightforward synthetic strategies for C–C
bond transformation.1 In particular, nickel-catalyzed cou-
R2CHO
R1
R1
+
+
pling reaction involving unsaturated hydrocarbons are
widely utilized for the synthesis of physiologically active
compounds and complicated molecules.2
R2
cat. Ni(acac)2
Me2Zn
R1
OH
R1
We have previously developed nickel-catalyzed C–C
bond formations by four-component coupling of buta-1,3-
diene, alkynes, aldehydes, and dimethylzinc to provide
octa-3,6-dienyl alcohols with excellent regio- and stereo-
selectivities (Scheme 2).3
R2CHO
+
+
R3NH2
R1
R1
+
R2
Under similar conditions, aldimines also participated in a
similar multicomponent coupling reaction to afford octa-
3,6-dienylamines and dodeca-3,7,10-trienylamines in rea-
sonable yields.4 Recently, we have shown that norbornene
served as an active unsaturated hydrocarbon in place of al-
kynes and underwent the nickel-catalyzed coupling reac-
cat. Ni(acac)2
Me2Zn
R1
NHR3
R1
Scheme 2 Multicomponent coupling of diene, alkyne, carbonyls,
and dimethylzinc
The above-mentioned reactions seem to proceed through
the oxidative cyclization of conjugated dienes and carbon-
SYNTHESIS 2012, 44, 2333–2339
Advanced online publication: 12.04.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0031-1290764; Art ID: SS-2012-Z0141-PSP
© Georg Thieme Verlag Stuttgart · New York

2334
T. Mori et al.
PRACTICAL SYNTHETIC PROCEDURES
Table 1 Initial Investigation for the Optimized Catalytic Systema
+
RCHO
+
Et
cat. Ni(acac)2
R
OH
+
Et
O
cat. Ni(acac)2
Me2Zn
Me2Zn
OH
Et
Et
1a
Entry Ligand
Solvent
Conditions
r.t., 24 h
Product 1a
Yield (%) Ratio E/Z
R2NH2
+
R1CHO
+
+
1
2
none
none
none
none
none
none
Ph3P
Bu3P
dppf
NHC
THF
92
3:1
3:1
3:1
3:1
3:1
3:1
3:1
–
R1
cat. Ni(acac)2
ligand
THF
50 °C, 24 h 89
NHR2
3
Et2O
r.t., 24 h
r.t., 24 h
r.t., 24 h
r.t., 24 h
r.t., 48 h
r.t., 48 h
r.t., 48 h
r.t., 24 h
84
81
59
20
71
Me2Zn
4
toluene
CH2Cl2
dioxane
THF
Scheme 3 Multicomponent coupling of diene, norbornene, carbonyls,
and dimethylzinc
5
6
yls to form a π-allylnickel intermediate that governs the
high regio- and stereoselectivity.
7
b
8
THF
–
Furthermore, the three-component coupling reaction of
allyl halides, alkynes, and dimethylzinc in the presence of
nickel catalyst via syn-stereoselective addition of π-allyl-
nickel species followed by methyl group transfer to the
alkyne carbon atom to construct the penta-1,4-diene skel-
eton has been previously reported (Scheme 4).6 Nickel-
catalyzed multicomponent coupling reactions of alkyne-
tethered vinylcyclopropanes with allylic halides through
the addition of π-allylnickel species to the C–C triple
bonds giving (E)-1,3-diene analogues were also demon-
strated.7
b
9
THF
–
–
10
THF
81
1:1
a Reaction conditions: vinyl epoxide (1 mmol), Ni(acac)2 (0.1 mmol),
ligand (0.2 mmol), hex-3-yne (1 mmol), 1 M Me2Zn in hexane (1.2
mmol), solvent (3 mL), under N2.
b No reaction.
attacked on the terminal carbon atom of the vinylic posi-
tion via methyl group transfer from dimethylzinc in 1:1 to
3:1 ratio of E- and Z-isomers with respect to the C2 olefin
geometry of hepta-2,5-dienyl alcohol 1a. Among these re-
sults with various kinds of ligands using monodentate, bi-
dentate phosphine ligands, and NHC ligands, their use at
room temperature did not provide improved results in the
formation of the desired product 1a.
cat. NiCl2(PPh3)2
X
+
R
R
Me2Zn
H
Scheme 4 Nickel-catalyzed coupling of allyl halides, alkyne, and di-
methylzinc
Based on this optimized catalytic systems, we examined
the multicomponent coupling reaction of vinyl epoxide
and substituted alkynes, and dimethylzinc on a multigram
scale to give the corresponding dienyl alcohols 1 in good
to reasonable yields (Table 2).
Encouraged by these studies, we report here the highly re-
gio- and stereocontrolled three-component coupling reac-
tions
of
alkynes,
dimethylzinc,
and
vinyl
epoxides/vinylcyclopropanes involving the addition of π-
allylnickel species to the alkynes to provide hepta-2,5-di-
enyl alcohols and dimethyl α-(hepta-2,5-dienyl)malo-
nates (Scheme 1, procedures 1 and 2).
Hex-3-yne and diphenylacetylene participated in the cou-
pling reaction with butadiene monoxide to afford 1a and
1b, respectively, in quantitative yields as a mixture of E-
and Z-stereoisomers (Table 2, entries 1 and 2). Bis(tri-
methylsilyl)acetylene provided the marginal success in
the coupling reaction (entry 3). The reaction using elec-
tron-deficient alkynes, such as bis(methoxycarbon-
yl)ethyne did not proceed at all (not shown in Table 2).
Unsymmetrical alkynes took part in the coupling reaction
in excellent yields to give 1d as four inseparable regio-
and stereoisomers and 1e as two stereoisomers (entries 4
and 5). Two equivalents of terminal alkynes were required
to afford the products 1f and 1g in modest yields along
with the branched regioisomers 2f and 2g, which were
produced by attack of the terminal alkynes on the internal
allylic position of the vinyl epoxide.
Scope and Limitations
The reaction was conducted by exposing dimethylzinc to
a mixture of vinyl epoxide and hex-3-yne in the presence
of bis(acetylacetonato)nickel [Ni(acac)2] catalyst under a
nitrogen atmosphere. The results using various kinds of li-
gands and solvents are shown in Table 1.8
The initial investigation using vinyl epoxide and hex-3-
yne made it clear that tetrahydrofuran was the most effec-
tive solvent (Table 1, entries 1–6). In all cases, hex-3-yne
Synthesis 2012, 44, 2333–2339
© Georg Thieme Verlag Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Nickel-Catalyzed MCRs
2335
Table 2 Coupling Reaction of Various Alkynes, Vinyl Epoxides, and Dimethylzinc on a 15-mmol Scale (Scheme 1, Procedure 1)a
R2
R1
cat. Ni(acac)2
OH
OH
+
R3
+
R3
R1
O
Me2Zn
r.t., 24 h
R2
2 (R1 = H)
R2
R3
1
R1
R2
R3
Entry
Products
1
2
Yield (%)
Ratio E/Z
Yield (%)
1
2
H
Et
Et
1a: 99
1b: 99
1c: 41
1d: 95
1e: 97
1f: 37
1g: 27
1h: 93
1i: 84
1j: 41
3:1
H
Ph
Ph
2:1
3
H
TMS
Et
TMS
Ph
2:1
4
H
8:4:2:1
2:1
5
H
Me
H
TMS
Ph
6b
7b
8
H
2:1
2f: 18
2g: 10
H
H
TMS
Et
2:1
Me
Me
Me
Et
1:2
9
Ph
Ph
1:3
10
TMS
TMS
1:1
a Reaction conditions: vinyl epoxide (18 mmol), Ni(acac)2 (0.15 mmol), alkyne (15 mmol), 1.0 M Me2Zn in hexane (15 mmol), THF (30 mL),
r.t., 24 h, under N2.
b Using vinyl epoxide (15 mmol), Ni(acac)2 (0.15 mmol), alkyne (30 mmol), 1.0 M Me2Zn in hexane (15 mmol).
Isoprene monoxide underwent a similar coupling reaction The coupling reaction with various alkynes, dimethylzinc,
in good to excellent yields, and employment of hex-3-yne and vinylcyclopropane, which is prepared from dimethyl
and diphenylacetylene led to the formation of the desired malonate with 1,4-dichlorobut-2-ene, are summarized in
product 1h and 1i in high yields in a 1:2 to 1:3 ratios of E- Table 3. In most cases, the three-component coupling re-
and Z-stereoisomers (entries 8 and 9). Bis(trimethylsi- action proceeded at room temperature to provide the cou-
lyl)acetylene showed modest yield and selectivity as well pling products 3 in good yields with excellent E-
as the result of butadiene monoxide (entry 10).
stereoselectivity (entries 1 and 2). Bis(trimethylsilyl)acet-
Table 3 Coupling Reaction of Alkynes, Vinylcyclopropane, and Dimethylzinc on a 15-mmol Scale (Scheme 1, Procedure 2)a
R2
R1
R2
E
cat. Ni(acac)2
E
R2
+
E
+
Me2Zn
r.t., 24 h
E
E
R1
R2
E
E = CO2Me
3
4 (R1 = H)
R1
R2
Entry
Yield (%)
Ratio E/Z
1
2
3
4
5
6c
Et
Et
3a: 80
3b: 68
3c: 59
3d: 83
3e: 91
4f: 65
7:1
Ph
TMS
Et
Ph
E only
E only
E only (3:1)b
E only
E only
TMS
Ph
Me
H
TMS
Ph
a Reaction conditions: vinylcyclopropane (15 mmol), Ni(acac)2 (0.15 mmol), alkyne (15 mmol), 1.0 M Me2Zn in hexane (15 mmol), THF (30
mL), r.t., 24 h, under N2.
b Product 3d was obtained as a mixture of regioisomer in 3:1.
c Using vinylcyclopropane (15 mmol), Ni(acac)2 (0.15 mmol), phenylacetylene (45 mmol), 1.0 M Me2Zn in hexane (15 mmol).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2333–2339

2336
T. Mori et al.
PRACTICAL SYNTHETIC PROCEDURES
(38.5 mg, 0.15 mmol). The apparatus was purged with N2 and the
flask was charged successively via syringe with fresh anhyd THF
(30 mL), butadiene monoxide (1.26 g, 18 mmol), and hex-3-yne
(1.23 g, 15 mmol). 1.0 M Me2Zn in hexane was added slowly at r.t.
via the dropping funnel over a period of 10 min (the reaction tem-
perature should not exceed 50 °C). The mixture was stirred at r.t. for
24 h (TLC monitoring). After the reaction was complete, the mix-
ture was cooled to 0 °C, and then poured into ice-water. The result-
ing soln was diluted with EtOAc (30 mL) and carefully washed with
2 M HCl (20 mL) and separated, and the aqueous layer was extract-
ed with EtOAc (50 mL). The combined organic phases were washed
with sat. NaHCO3 and brine, dried (MgSO4) and concentrated in
vacuo. The residual oil was subjected to column chromatography
(silica gel, hexane–EtOAc, 16:1) to afford 1a (2.51 g, 99%) as a col-
orless oil; ratio E/Z 3:1; Rf = 0.45 (hexane–EtOAc, 4:1); bp 100
°C/0.13 mbar.
ylene took part in the efficient coupling reaction to afford
the desired product 3c with exclusive E-selectivity in rea-
sonable yield (entry 3). Unsymmetrical internal alkynes
also participated in the coupling reaction. 1-Phenylbut-1-
yne provided 3d as regioisomers in a 3:1 ratio with excel-
lent E-stereoselectivity, whereas 1-(trimethylsilyl)prop-1-
yne gave 3e as a single isomer with excellent E-stereose-
lectivity. In all cases, the stereochemistry with respect to
the methyl group and the olefin main chain is the Z-form,
as in the reaction of vinylcyclopropane. The reaction us-
ing a terminal alkyne, such as phenylacetylene, changed
dramatically and the desired product 3f was not obtained.
Instead, dienyne 4f was produced exclusively via dimer-
ization of terminal alkyne followed by stereoselective
coupling reaction with vinylcyclopropane.
IR (neat): 3319 (m), 2962 (s), 2931 (s), 2872 (s), 1655 (w), 1373
(m), 1070 (m), 1004 (m), 970 (m), 792 cm–1 (w).
1H NMR (400 MHz, CDCl3): δ (E-isomer) = 0.94 (t, J = 7.6 Hz, 3
H), 0.97 (t, J = 7.6 Hz, 3 H), 1.62 (s, 3 H), 2.03 (q, J = 7.6 Hz, 2 H),
2.04 (q, J = 7.6 Hz, 2 H), 2.75 (m, 2 H), 4.09 (m, 2 H), 5.62 (m, 2 H).
Conclusions
1H NMR (400 MHz, CDCl3): δ (Z-isomer) = 0.94 (t, J = 7.6 Hz, 3
H), 0.97 (t, J = 7.6 Hz, 3 H), 1.58 (s, 3 H), 2.03 (q, J = 7.6 Hz, 2 H),
2.04 (q, J = 7.6 Hz, 2 H), 2.80 (d, J = 7.3 Hz, 2 H), 4.26 (m, 2 H),
5.45 (dt, J = 11.0, 7.3 Hz, 1 H), 5.58 (dm, J = 11.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ (E-isomer) = 13.3, 13.6, 17.5, 24.9,
27.0, 34.7, 63.8, 127.9, 128.8, 131.2, 131.6.
In summary, we have demonstrated that the nickel-cata-
lyzed multicomponent coupling reaction of vinyl epox-
ides, alkynes, and dimethylzinc provides hepta-2,5-dienyl
alcohols as mixtures of E- and Z-isomers in high yields.
Furthermore, vinylcyclopropane participated in a highly
regio- and stereoselective multicomponent coupling reac-
tion to afford dimethyl α-(hepta-2,5-dienyl)malonates
with excellent E-stereoselectivity. We have succeeded in
extending these reactions to the multigram scale for the
efficient synthesis of dienyl alcohols and stereodefined di-
enyl esters. These reactions could be performed with stan-
dard laboratory glassware and equipment and did not
require expensive and specialized chemicals and cata-
lysts.
13C NMR (100 MHz, CDCl3): δ (Z-isomer) = 13.2, 13.6, 17.5, 24.8,
27.1, 30.2, 58.7, 127.9, 128.8, 131.0, 131.4.
HRMS: m/z [M]+ calcd for C11H20O: 168.1514; found (%): 169 ([M
+ 1]+, 1), 168.1497 (M+, 8), 167 (20), 151 (27), 150 (31), 139 (100).
(2E/Z,5Z)-5,6-Diphenylhepta-2,5-dien-1-ol (1b)
Following typical procedure 1. Purification by flash chromatogra-
phy (hexane–EtOAc, 8:1) afforded 1b (3.93 g, 99%) as a colorless
oil; ratio E/Z 2:1; bp 180 °C/0.13 mbar.
IR (neat): 3350 (s), 3055 (s), 3020 (s), 2993 (s), 2928 (s), 2870 (m),
1717 (s), 1682 (s), 1599 (m), 1489 (s), 1443 (s), 1026 (m), 970 (m),
912 (m), 764 cm–1 (m).
1H NMR (400 MHz, CDCl3): δ (E-isomer) = 2.17 (s, 3 H), 3.31 (m,
All reactions were carried out under an N2 atmosphere in dried
glassware. Ni(acac)2 (Aldrich), and 1.0 M Me2Zn in hexane (Kanto
Kagaku) were purchased and used without further purification.
2 H), 4.10 (m, 2 H), 5.72 (m, 2 H), 7.00 (m, 10 H).
Hex-3-yne,
diphenylacetylene,
bis(trimethylsilyl)acetylene,
1H NMR (400 MHz, CDCl3): δ (Z-isomer) = 2.20 (s, 3 H), 3.34 (d,
J = 6.6 Hz, 2 H), 4.00 (d, J = 6.3 Hz, 2 H), 5.57 (dt, J = 10.2, 6.6 Hz,
1 H), 5.72 (dt, J = 10.2, 6.3 Hz, 1 H), 6.90–7.10 (m, 10 H).
13C NMR (100 MHz, CDCl3): δ (E-isomer) = 21.1, 37.9, 63.6,
125.6, 127.4, 127.5, 128.9, 129.0, 129.4, 129.5, 129.6, 134.7, 142.8,
143.1, 144.1.
13C NMR (100 MHz, CDCl3): δ (Z-isomer) = 20.9, 33.5, 58.4,
125.8, 127.4, 127.5, 128.9, 129.3, 129.4, 129.5, 129.6, 135.4, 142.8,
143.1, 144.0.
bis(methoxycarbonyl)ethyne, phenylacetylene, trimethylsilylacety-
lene, 1-phenylbut-1-yne, and 1-(trimethylsilyl)prop-1-yne (Tokyo
Kasei Kogyo Co., Ltd) were purchased and distilled prior to use.
Butadiene monoxide and isoprene oxide (Aldrich) were purchased
and distilled prior to use. Dimethyl 2-vinylcyclopropane-1,1-dicar-
boxylate was prepared according to the literature.9 THF was dried
and distilled from benzophenone and Na immediately prior to use
under N2. TLC employed glass 0.25 mm silica gel plates with UV
indicator (Merck, Silica gel 60F254). Flash chromatography col-
umns were packed with 230–400 mesh silica gel as a slurry in hex-
ane. Gradient flash chromatography was conducted eluting with a
continuous gradient from hexane to the indicated solvent. Unless
otherwise specified, short-path (bulb-to-bulb) distillations were car-
ried out in a Kugelrohr apparatus, in these cases, boiling points refer
to the oven temperature. 1H and 13C NMR data were obtained with
a Jeol-GX400 with TMS as internal standard. Infrared spectra were
recorded with a Jasco A-100 FT-IR spectrophotometer. HRMS
were measured with a Jeol JMS-DX303.
HRMS: m/z [M]+ calcd for C19H20O: 264.1514; found (%):
264.1440 (M+, 42), 263 (100), 262 (51), 246 (57).
(2E/Z,5Z)-5,6-Bis(trimethylsilyl)hepta-2,5-dien-1-ol (1c)
Following typical procedure 1. Purification by flash chromatogra-
phy (hexane–EtOAc, 12:1) afforded 1c (1.58 g, 41%) as a colorless
oil; ratio E/Z 2:1; bp 110 °C/0.13 mbar.
IR (neat): 3329 (m), 2955 (s), 2899 (m), 2864 (m), 1456 (w), 1248
(s), 1001 (m), 968 (m), 837 (s), 756 cm–1 (m).
1H NMR (400 MHz, CDCl3): δ = 0.12 (s, 18 H), 1.26 (br, 1 H), 1.78
(s, 3 H), 2.89 (d, J = 7.6 Hz, 2 H), 4.26 (d, J = 6.3 Hz, 2 H), 5.60–
5.68 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ (E-isomer) = 0.4, 17.6, 33.4, 63.8,
128.6, 130.3, 142.9.
(2E/Z,5E)-5-Ethyl-6-methylocta-2,5-dien-1-ol (1a); Typical
Procedure 1
An oven-dried, 100-mL, 4-necked round-bottomed flask equipped
with a dropping funnel, thermometer, rubber septum cap, air con-
denser (fitted with a 3-way stopcock connected into an N2 balloon),
and Teflon-coated magnetic stir bar was charged with Ni(acac)2
Synthesis 2012, 44, 2333–2339
© Georg Thieme Verlag Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Nickel-Catalyzed MCRs
2337
13C NMR (100 MHz, CDCl3): δ (Z-isomer) = 0.4, 17.6, 31.6, 60.3,
128.6, 130.3, 143.3.
Hz, 1 H), 7.30 (td, J = 7.0, 1.5 Hz, 2 H), 7.36 (dt, J = 7.0, 1.3 Hz, 2
H).
HRMS: m/z [M]+ calcd for C13H28OSi2: 256.1679; found (%): 257
1H NMR (400 MHz, CDCl3): δ (Z-isomer) = 1.55 (br, 1 H), 2.05 (t,
J = 1.0 Hz, 3 H), 2.95 (t J = 7.0 Hz, 2 H), 4.12 (d, J = 5.3 Hz, 1 H),
4.27 (d, J = 5.3 Hz, 1 H), 5.60–5.80 (m, 3 H), 7.21 (tt, J = 7.0, 2.0
Hz, 1 H), 7.30 (td, J = 7.0, 1.5 Hz, 2 H), 7.36 (dt, J = 7.0, 1.3 Hz, 2
H).
13C NMR (100 MHz, CDCl3): δ (E-isomer) = 15.8, 31.4, 63.6,
125.5, 126.6, 128.0, 128.2, 129.4, 130.7, 135.9, 143.5.
([M + 1]+, 24), 256.1679 (M+, 100), 225 (9).
(2E,5E)-5-Ethyl-6-phenylhepta-2,5-dien-1-ol (1d)
Following typical procedure 1. Purification by flash chromatogra-
phy (hexane–EtOAc, 8:1) afforded 1d (3.09 g, 95%) as a colorless
oil; a mixture of 4 isomers in the ratio 8:4:2:1, minor regioisomers
were not assigned; bp 150 °C/0.13 mbar.
13C NMR (100 MHz, CDCl3): δ (Z-isomer) = 15.8, 27.3, 58.6,
125.5, 126.6, 128.0, 128.2, 128.8, 130.7, 135.6, 143.4.
IR (neat): 3350 (s), 3057 (m), 3020 (m), 2968 (s), 2933 (s), 2873 (s),
1717 (s), 1682 (s), 1599 (m), 1491 (s), 1441 (s), 1026 (s), 972 (m),
766 cm–1 (s).
1H NMR (400 MHz, CDCl3): δ (2E-isomer) = 0.89 (t, J = 7.6 Hz, 3
H), 1.58 (br s, 1 H), 1.89 (q, J = 7.6 Hz, 2 H), 1.93 (s, 3 H), 2.94 (m,
2 H), 4.14 (m, 2 H), 5.73 (m, 2 H), 7.10 (t, J = 7.6 Hz, 2 H), 7.21 (d,
J = 7.6 Hz, 2 H), 7.30 (t, J = 7.6 Hz, 1 H).
1H NMR (400 MHz, CDCl3): δ (2Z-isomer) = 0.90 (t, J = 7.6 Hz, 3
H), 1.31 (br s, 1 H), 1.89 (q, J = 7.6 Hz, 2 H), 1.95 (s, 3 H), 2.98 (d,
J = 7.3 Hz, 2 H), 4.31 (d, J = 6.6 Hz, 2 H), 5.56 (dt, J = 10.7, 7.3 Hz,
1 H), 5.67 (dt, J = 10.7, 6.6 Hz, 1 H), 7.10 (t, J = 7.6 Hz, 2 H), 7.21
(d, J = 7.6 Hz, 2 H), 7.29 (t, J = 7.6 Hz, 1 H).
HRMS: m/z [M]+ calcd for C13H16O: 188.1183; found (%): 189 ([M
+ 1]+, 8), 188.1183 (M+, 54), 171 (13), 157 (48).
(E)-4-Phenyl-2-vinylpent-3-en-1-ol (2f)
Yield: 508 mg (18%); Rf = 0.53 (hexane–EtOAc, 4:1).
IR (neat): 3362 (br), 3080 (s), 2928 (s), 2872 (s), 1726 (s), 1636 (m),
1597 (m), 1493 (m), 914 (m), 758 (s), 696 cm–1 (s).
1H NMR (400 MHz, CDCl3): δ = 1.54 (s, 1 H), 2.09 (d, J = 1.5 Hz,
3 H), 3.38 (ddt, J = 10.3, 9.0, 7.4 Hz, 1 H), 3.62 (d, J = 7.4 Hz, 2 H),
5.17 (dd, J = 7.6, 1.5 Hz, 1 H), 5.20 (dd, J = 17.3, 1.5 Hz, 1 H), 5.63
(dq, J = 9.0, 1.5 Hz, 1 H), 5.78 (ddd, J = 17.3, 10.3, 7.6 Hz, 1 H),
7.24 (tt, J = 7.9, 2.3 Hz, 1 H), 7.31 (td, J = 7.9, 1.5 Hz, 2 H), 7.39
(dt, J = 7.9, 1.3 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ (2E-isomer) = 13.4, 21.0, 26.2,
33.8, 63.7, 125.8, 127.8, 127.9, 128.5, 129.3, 130.4, 130.9, 144.9.
13C NMR (100 MHz, CDCl3): δ (2Z-isomer) = 13.3, 20.9, 26.1,
29.4, 58.7, 125.8, 127.9, 127.9, 128.6, 129.2, 130.4, 130.9, 144.9.
13C NMR (100 MHz, CDCl3): δ = 16.4, 46.3, 65.5, 116.5, 125.6,
125.9, 126.9, 128.1, 137.4, 138.0, 143.3.
HRMS: m/z [M]+ calcd for C15H20O: 216.1514; found (%): 217 ([M
HRMS: m/z [M]+ calcd for C13H16O: 188.1183; found (%): 189 ([M
+ 1]+, 16), 216.1496 (M+, 100), 214 (15), 199 (36).
+ 1]+, 7), 188.1183 (M+, 46), 157 (100), 142 (76).
(2E/Z,5E)-5-Methyl-6-(trimethylsilyl)hepta-2,5-dien-1-ol (1e)
Following typical procedure 1. Purification by flash chromatogra-
phy (hexane–EtOAc, 16:1) afforded 1e (2.89 g, 97%) as a colorless
oil; ratio E/Z 2:1; bp 115 °C/0.13 mbar.
(2E/Z,5E)-6-(Trimethylsilyl)hepta-2,5-dien-1-ol (1g) and
(E)-4-(Trimethylsilyl)-2-vinylpent-3-en-1-ol (2g)
Following typical procedure 1 using Ni(acac)2 (38.5 mg, 0.15
mmol), butadiene monoxide (1.05 g, 15 mmol), trimethylsilylacet-
ylene (2.95 g, 30 mmol), and 1.0 M Me2Zn in hexane (15 mmol) in
anhyd THF (30 mL). Purification by flash column chromatography
(hexane–EtOAc, 10:1) afforded 1g and 2g both as colorless oils
with bp 110 °C/0.13 mbar.
IR (neat): 3312 (s), 2953 (s), 2912 (s), 2860 (m), 1612 (m), 1445
(m), 1247 (s), 1001 (m), 835 (s), 756 (s), 687 cm–1 (m).
1H NMR (400 MHz, CDCl3): δ (E-isomer) = 0.12 (s, 9 H), 1.26 (br
s, 1 H), 1.70 (s, 3 H), 1.78 (s, 3 H), 2.84 (d, J = 7.4 Hz, 2 H), 4.09
(d, J = 6.3 Hz, 2 H), 5.45–5.65 (m, 2 H).
1H NMR (400 MHz, CDCl3): δ (Z-isomer) = 0.13 (s, 9 H), 1.35 (br
s, 1 H), 1.71 (s, 3 H), 1.85 (s, 3 H), 2.89 (d, J = 7.4 Hz, 2 H), 4.25
(d, J = 6.3 Hz, 2 H), 5.45–5.65 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ (E-isomer) = 0.4, 17.6, 21.1, 37.9,
63.7, 128.4, 129.2, 131.9, 142.9.
13C NMR (100 MHz, CDCl3): δ (Z-isomer) = 0.7, 17.6, 22.9, 34.3,
(2E/Z,5E)-6-(Trimethylsilyl)hepta-2,5-dien-1-ol (1g)
Yield: 756 mg (27%); ratio E/Z 2:1 Rf = 0.46 (hexane–EtOAc, 4:1).
IR (neat): 3317 (br), 3009 (s), 2955 (s), 2899 (s), 1614 (m), 1248 (s),
1013 (s), 970 (s), 837 (s), 750 (s), 689 cm–1 (s).
1H NMR (400 MHz, CDCl3): δ (E-isomer) = 0.01 (s, 9 H), 1.28 (s,
1 H), 1.63 (d, J = 0.9 Hz, 3 H), 2.84 (t, J = 6.9 Hz, 2 H), 4.06 (d,
J = 5.6 Hz, 2 H), 5.62 (m, 3 H).
1H NMR (400 MHz, CDCl3): δ (Z-isomer) = 0.01 (s, 9 H), 1.28 (s,
1 H), 1.65 (d, J = 0.9 Hz, 3 H), 2.81 (t, J = 6.9 Hz, 2 H), 4.19 (d,
J = 5.6 Hz, 2 H), 5.62 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ (E-isomer) = –2.1, 14.4, 31.2, 63.7,
128.5, 129.1, 131.0, 135.9.
13C NMR (100 MHz, CDCl3): δ (Z-isomer) = –2.1, 14.4, 27.0, 58.6,
128.5, 129.1, 131.0, 135.9.
58.6, 128.6, 129.8, 130.3, 144.7.
HRMS: m/z [M]+ calcd for C11H22OSi: 198.1440; found (%): 199
([M + 1]+, 10), 198.1431 (M+, 60), 183 (20), 169 (16), 127 (100).
(2E/Z,5E)-6-Phenylhepta-2,5-dien-1-ol (1f) and
(E)-4-Phenyl-2-vinylpent-3-en-1-ol (2f)
Following typical procedure 1 using Ni(acac)2 (38.5 mg, 0.15
mmol), butadiene monoxide (1.05 g, 15 mmol), phenylacetylene
(3.06 g, 30 mmol), and 1 M Me2Zn in hexane (15 mmol) in anhyd
THF (30 mL). Purification by flash column chromatography (hex-
ane–EtOAc, 6:1) afforded 1f and 2f both as colorless oils with bp
160 °C/0.13 mbar.
HRMS: m/z [M]+ calcd for C10H20OSi: 184.1283; found (%): 185
([M + 1]+, 16), 184.1261 (M+, 100), 170 (12), 169 (82), 166 (34).
(E)-4-(Trimethylsilyl)-2-vinylpent-3-en-1-ol (2g)
Yield: 276 mg (10%), Rf = 0.50 (hexane–EtOAc, 4:1).
(2E/Z,5E)-6-Phenylhepta-2,5-dien-1-ol (1f)
Yield: 1.05 g (37%); ratio E/Z 2:1; Rf = 0.50 (hexane–EtOAc, 4:1).
IR (neat): 3313 (br), 3080 (m), 2955 (s), 2874 (m), 1618 (m), 1248
(s), 1028 (s), 991 (m), 835 (s), 750 (s), 689 cm–1 (m).
IR (neat): 3371 (br), 3024 (s), 2926 (s), 2872 (s), 1719 (m), 1647
(m), 1495 (s), 1447 (s), 1028 (s), 927 (s), 760 (s), 698 cm–1 (s).
1H NMR (400 MHz, CDCl3): δ (E-isomer) = 1.55 (br, 1 H), 2.05 (t,
J = 1.0 Hz, 3 H), 2.99 (t, J = 7.0 Hz, 2 H), 4.12 (d, J = 5.3 Hz, 1 H),
4.27 (d, J = 5.3 Hz, 1 H), 5.60–5.80 (m, 3 H), 7.21 (tt, J = 7.0, 2.0
1H NMR (400 MHz, CDCl3): δ = 0.07 (s, 9 H), 1.43 (s, 1 H), 1.73
(d, J = 1.7 Hz, 3 H), 3.38 (tdd, J = 8.5, 7.8, 6.7 Hz, 1 H), 3.52 (d,
J = 7.8 Hz, 2 H), 5.11 (dd, J = 17.6, 1.7 Hz, 1 H), 5.12 (dd, J = 9.8,
1.7 Hz, 1 H), 5.53 (dq, J = 8.5, 1.7 Hz, 1 H), 5.72 (ddd, J = 17.6, 9.8,
6.7 Hz, 1 H).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2333–2339

2338
T. Mori et al.
PRACTICAL SYNTHETIC PROCEDURES
13C NMR (100 MHz, CDCl3): δ = 1.6, 15.4, 46.3, 65.6, 116.7,
136.5, 137.9, 140.9.
13C NMR (100 MHz, CDCl3): δ (Z-isomer) = 0.81, 1.46, 13.9, 18.7,
25.4, 69.1, 124.3, 133.4, 143.9, 149.8.
HRMS: m/z [M]+ calcd for C10H20OSi: 184.1283; found (%): 185
13C NMR (100 MHz, CDCl3): δ (E-isomer) = 0.81, 1.93, 18.7, 20.2,
25.4, 61.9, 125.9, 133.5, 143.9, 151.2.
([M + 1]+, 16), 184.1261 (M+, 100), 170 (12), 169 (82), 166 (34).
HRMS: m/z [M]+ calcd for C14H30OSi2: 270.1835; found (%):
(2Z/E,5E)-5-Ethyl-2,6-dimethylocta-2,5-dien-1-ol (1h)
Following typical procedure 1 using isoprene monoxide instead of
butadiene monoxide. Purification by flash chromatography (hex-
ane–EtOAc, 16:1) afforded 1h (2.54 g, 93%) as a colorless oil; ratio
E/Z 1:2; bp 105 °C/0.13 mbar.
270.1812 (M+, 100), 269 (72), 254 (94).
Dimethyl 2-[(2E/Z,5E)-5-Ethyl-6-methylocta-2,5-dienyl]malo-
nate (3a); Typical Procedure 2
An oven-dried, 100-mL, 4-necked round-bottomed flask equipped
with a dropping funnel, a thermometer, a rubber septum cap, an air
condenser (fitted with a 3-way stopcock connected into N2 balloon),
and a Teflon-coated magnetic stir bar was charged with Ni(acac)2
(38.5 mg, 0.15 mmol). The apparatus was purged with N2 and the
flask was charged successively via syringe with fresh anhyd THF
(30 mL), vinylcyclopropane (2.76 g, 15 mmol), and hex-3-yne (1.23
g, 15 mmol). 1.0 M Me2Zn in hexane (15 mmol) was added slowly
via the dropping funnel over a period of 10 min (the reaction tem-
perature should not exceed 50 °C). The mixture was stirred at r.t. for
24 h (TLC monitoring). After the reaction was completed, the mix-
ture was cooled to 0 °C, and then poured into ice-water. The result-
ing soln was diluted with EtOAc (30 mL) and carefully washed with
2 M HCl (20 mL) and separated, and the aqueous layer was extract-
ed with EtOAc (50 mL). The combined organic phases were washed
with sat. NaHCO3 and brine, dried (MgSO4) and concentrated in
vacuo. The residual oil was subjected to column chromatography
(silica gel, hexane–EtOAc, 25:1) to afford 3a (3.38 g, 80%) as a col-
orless oil; ratio E/Z 7:1; Rf = 0.60 (hexane–EtOAc, 4:1); bp 130
/0.13 mbar.
IR (neat): 3336 (m), 2964 (s), 2934 (s), 2872 (s), 1653 (m), 1456 (s),
1375 (s), 1005 (s), 951 (w), 785 cm–1 (w).
1H NMR (400 MHz, CDCl3): δ (Z-isomer) = 0.94 (t, J = 7.6 Hz, 3
H), 0.96 (t, J = 7.6 Hz, 3 H), 1.64 (s, 3 H), 1.80 (q, J = 1.2 Hz, 3 H),
1.99 (q, J = 7.6 Hz, 2 H), 2.02 (q, J = 7.6 Hz, 2 H), 2.77 (d, J = 7.1
Hz, 2 H), 4.19 (s, 2 H), 5.31 (tq, J = 7.1, 1.2 Hz, 1 H).
1H NMR (400 MHz, CDCl3): δ (E-isomer) = 0.94 (t, J = 7.6 Hz, 3
H), 0.96 (t, J = 7.6 Hz, 3 H), 1.64 (s, 3 H), 1.72 (s, 3 H), 1.99 (q, J
= 7.6 Hz, 2 H), 2.02 (q, J = 7.6 Hz, 2 H), 2.75 (d, J = 6.6 Hz, 2 H),
4.00 (s, 2 H), 5.21 (t, J = 6.6 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ (Z-isomer) = 13.2, 13.6, 17.5, 21.3,
24.6, 27.1, 30.2, 61.7, 127.2, 130.5, 132.2, 133.7.
13C NMR (100 MHz, CDCl3): δ (E-isomer) = 13.2, 13.6, 13.8, 17.6,
24.9, 27.1, 30.4, 69.1, 125.4, 130.5, 132.3, 134.2.
HRMS: m/z [M]+ calcd for C12H22O: 182.1671; found (%): 183 ([M
+ 1]+, 10), 182.1669 (M+, 69), 164 (100).
(2Z/E,5Z)-2-Methyl-5,6-diphenylhepta-2,5-dien-1-ol (1i)
Following typical procedure 1 using isoprene monoxide instead of
butadiene monoxide. Purification by flash chromatography (hex-
ane–EtOAc, 12:1) afforded 1i (3.51 g, 84%) as a colorless oil; ratio
E/Z 1:3; bp 170 °C /0.13 mbar.
IR (neat): 2959 (s), 2882 (m), 1738 (s), 1655 (w), 1437 (s), 1340
(m), 1269 (m), 1161 (m), 974 (m), 698 cm–1 (w).
1H NMR (400 MHz, CDCl3): δ (E-isomer) = 0.91 (t, J = 7.6 Hz, 3
H), 0.96 (t, J = 7.6 Hz, 3 H), 1.54 (s, 3 H), 1.97 (q, J = 7.6 Hz, 2 H),
2.02 (q, J = 7.6 Hz, 2 H), 2.58 (ddd, J = 7.8, 6.8, 1.2 Hz, 2 H), 2.67
(d, J = 6.1 Hz, 2 H), 3.40 (t, J = 7.8 Hz, 1 H), 3.71 (s, 6 H), 5.32 (dt,
J = 15.1, 6.8 Hz, 1 H), 5.46 (dtt, J = 15.1, 6.1, 1.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ (E-isomer) = 13.3, 13.6, 17.5, 24.7,
27.0, 31.9, 35.0, 52.1, 52.3, 52.7, 124.9, 127.7, 131.1, 131.8, 169.2,
172.4.
IR (neat): 3350 (s), 3057 (m), 3024 (s), 2968 (s), 2933 (s), 2876 (s),
1719 (s), 1701 (s), 1670 (m), 1599 (m), 1491 (s), 1437 (s), 1026 (m),
912 (m), 760 cm–1 (m).
1H NMR (400 MHz, CDCl3): δ (Z-isomer) = 1.55 (br s, 1 H), 1.74
(d, J = 1.2 Hz, 3 H), 2.20 (s, 3 H), 3.30 (d, J = 7.6 Hz, 2 H), 3.91 (s,
2 H), 5.31 (tq, J = 7.6, 1.2 Hz, 1 H), 6.92–7.08 (m, 10 H).
1H NMR (400 MHz, CDCl3): δ (E-isomer) = 1.55 (br s, 1 H), 1.63
(d, J = 1.2 Hz, 3 H), 2.18 (s, 3 H), 3.30 (d, J = 7.6 Hz, 2 H), 3.97 (s,
2 H), 5.41 (tq, J = 6.8, 1.2 Hz, 1 H), 6.92–7.08 (m, 10 H).
13C NMR (100 MHz, CDCl3): δ (Z-isomer) = 13.2, 13.7, 17.6, 24.9,
26.9, 27.1, 30.0, 51.7, 52.4, 52.4, 124.9, 127.7, 131.1, 132.0, 169.3,
172.4.
HRMS: m/z [M]+ calcd for C16H26O4: 282.1831; found (%):
13C NMR (100 MHz, CDCl3): δ (Z-isomer) = 20.9, 21.3, 33.8, 61.5,
124.6, 125.7, 127.4, 127.5, 128.9, 129.6, 135.2, 136.0, 143.0, 144.1.
282.1829 (M+, 100), 253 (64), 251 (25).
13C NMR (100 MHz, CDCl3): δ (E-isomer) = 13.8, 21.1, 33.8, 68.8,
123.5, 125.5, 127.4, 127.5, 129.0, 129.4, 135.2, 136.0, 143.0, 144.1.
Dimethyl 2-[(2E,5Z)-5,6-Diphenylhepta-2,5-dienyl]malonate
(3b)
Following typical procedure 2. Purification by flash chromatogra-
phy (hexane–EtOAc, 16:1) afforded 3b (3.86 g, 68%) as a colorless
oil; bp 190 °C/0.13 mbar.
HRMS: m/z [M]+ calcd for C20H22O: 278.1671; found (%): 279 ([M
+ 1]+, 17), 278.1658 (M+, 73), 260 (100).
(2Z/E,5Z)-2-Methyl-5,6-bis(trimethylsilyl)hepta-2,5-dien-1-ol
(1j)
IR (neat): 3078 (w), 3020 (s), 2999 (m), 2953 (s), 1732 (s), 1599
(w), 1435 (s), 1198 (m), 1155 (s), 764 (s), 700 cm–1 (s).
Following typical procedure 1 using isoprene monoxide instead of
butadiene monoxide. Purification by flash chromatography (hex-
ane–EtOAc, 16:1) afforded 1j (1.65 g, 41%) as a colorless oil; ratio
E/Z 1:1; bp 170 °C/0.13 mbar.
1H NMR (400 MHz, CDCl3): δ = 2.13 (s, 3 H), 2.60 (ddd, J = 7.6,
6.8, 1.0 Hz, 2 H), 3.23 (d, J = 5.9 Hz, 2 H), 3.38 (t, J = 7.6 Hz, 1 H),
3.69 (s, 6 H), 5.46 (dt, J = 15.1, 6.8 Hz, 1 H), 5.58 (dtt, J = 15.1, 5.9,
1.0 Hz, 1 H), 6.90–7.06 (m, 10 H).
13C NMR (100 MHz, CDCl3): δ = 21.0, 31.9, 38.2, 52.0, 52.3, 52.4,
125.5, 125.6, 127.3, 127.4, 128.6, 128.9, 129.4, 134.5, 134.9, 138.9,
143.3, 144.2, 169.1.
IR (neat): 3396 (br), 2955 (s), 2899 (s), 1717 (s), 1699 (s), 1248 (s),
1047 (s), 1009 (s), 839 (s), 756 (s), 689 cm–1 (m).
1H NMR (400 MHz, CDCl3): δ (Z-isomer) = 0.14 (s, 9 H), 0.18 (s,
9 H), 1.72 (s, 3 H), 1.80 (br s, 1 H), 1.83 (s, 3 H), 2.85 (d, J = 6.7
Hz, 2 H), 4.19 (d, J = 4.2 Hz, 2 H), 5.04 (t, J = 6.7 Hz, 1 H).
1H NMR (400 MHz, CDCl3): δ (E-isomer) = 0.13 (s, 9 H), 0.17 (s,
9 H), 1.72 (s, 3 H), 1.80 (br s, 1 H), 1.83 (s, 3 H), 2.83 (d, J = 6.8
Hz, 2 H), 4.19 (d, J = 4.2 Hz, 2 H), 5.02 (t, J = 6.8 Hz, 1 H).
HRMS: m/z [M]+ calcd for C24H26O4: 378.1831; found (%): 379 ([M
+ 1]+, 27), 378.1835 (M+, 100), 360 (3).
Synthesis 2012, 44, 2333–2339
© Georg Thieme Verlag Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Nickel-Catalyzed MCRs
2339
Dimethyl 2-[(2E,5Z)-5,6-Bis(trimethylsilyl)hepta-2,5-di-
enyl]malonate (3c)
Following typical procedure 2. Purification by flash chromatogra-
phy (hexane–EtOAc, 20:1) afforded 3c (3.28 g, 59%) as a colorless
oil; bp 120 °C/0.13 mbar.
(4.60 g, 45 mmol), and 1.0 M Me2Zn in hexane (15 mmol) in anhyd
THF (30 mL). Purification by flash column chromatography (hex-
ane–EtOAc, 16:1) afforded 4f (3.80 g, 65%) as a yellow-colored oil;
Rf = 0.55 (hexane–EtOAc, 4:1).
IR (neat): 3028 (s), 2953 (s), 2843 (m), 1738 (s), 1597 (m), 1489 (s),
1435 (s), 1155 (s), 1028 (s), 970 (m), 914 (m), 758 (s), 692 cm–1 (s).
IR (neat): 2957 (s), 1736 (s), 1456 (m), 1437 (m), 1340 (m), 1248
(s), 1198 (s), 1155 (s), 972 (m), 839 cm–1 (m).
1H NMR (400 MHz, CDCl3): δ = 0.15 (s, 18 H), 1.76 (s, 3 H), 2.62
(d, J = 6.4 Hz, 2 H), 2.62 (t, J = 7.5 Hz, 2 H), 3.42 (t, J = 7.5 Hz, 1
H), 3.75 (s, 6 H), 5.64–5.46 (m, 2 H).
1H NMR (400 MHz, CDCl3): δ = 2.63 (td, J = 7.6, 1.0 Hz, 2 H),
3.25 (td, J = 6.9, 1.0 Hz, 2 H), 3.43 (t, J = 7.6 Hz, 1 H), 3.71 (s, 6
H), 5.53 (dtt, J = 15.4, 6.9, 1.3 Hz, 1 H), 5.65 (dtt, J = 15.4, 7.6, 1.3
Hz, 1 H), 6.37 (t, J = 7.6 Hz, 1 H), 7.27–7.37 (m, 6 H), 7.50–7.55
(m, 2 H), 7.62–7.65 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = –2.1, 22.8, 32.1, 52.3, 125.5,
13C NMR (100 MHz, CDCl3): δ = 31.9, 34.4, 51.8, 52.4, 86.4, 95.5,
123.3, 124.1, 125.9, 126.8, 127.5, 128.2, 130.4, 131.4, 135.2, 137.9,
169.1.
130.1, 143.2, 150.5, 169.3.
HRMS: m/z [M]+ calcd for C18H34O4Si2: 370.1996; found (%): 371
([M + 1]+, 22), 370.2006 (M+, 78), 355 (100), 339 (6).
HRMS: m/z [M]+ calcd for C25H24O4: 388.1675; found (%): 389 ([M
Dimethyl 2-[(2E,5E)-5-Ethyl-6-phenylhepta-2,5-dienyl]malo-
nate (3d)
+ 1]+, 28), 388.1689 (M+, 100), 373 (6), 357 (92), 329 (22).
Following typical procedure 2. Purification by flash chromatogra-
phy (hexane–EtOAc, 16:1) afforded 3d (4.11 g, 83%) as a colorless
oil; ratio of regioisomers 3:1; bp 140 °C/0.13 mbar.
Acknowledgement
This work was supported by Grants-in Aid for Scientific Research
(B) (21350055) and Scientific Research on Innovative Areas
‘Molecular Activation Directed toward Straightforward Synthesis’
from MEXT, Japan.
IR (neat): 3020 (m), 2959 (s), 2934 (s), 1738 (s), 1437 (s), 1232 (s),
1153 (s), 1026 (m), 970 (m), 768 (s), 704 cm–1 (s).
1H NMR (400 MHz, CDCl3): δ (major) = 0.86 (t, J = 7.4 Hz, 3 H),
1.85 (q, J = 7.4 Hz, 2 H), 1.90 (s, 3 H), 2.63 (td, J = 7.3, 1.2 Hz, 2
H), 2.85 (d, J = 6.2 Hz, 2 H), 3.44 (t, J = 7.3 Hz, 1 H), 3.72 (s, 6 H),
5.46 (dtt, J = 15.4, 7.3, 1.5 Hz, 1 H), 5.57 (dtt, J = 15.4, 6.2, 1.5 Hz,
1 H), 7.09 (dd, J = 7.5, 1.4 Hz, 2 H), 7.19 (tt, J = 7.5, 1.4 Hz, 1 H),
7.29 (td, J = 7.5, 1.4 Hz, 2 H).
1H NMR (400 MHz, CDCl3): δ (minor) = 0.90 (t, J = 7.4 Hz, 3 H),
1.75 (s, 3 H), 1.91 (q, J = 7.4 Hz, 2 H), 2.55 (td, J = 7.3, 1.2 Hz, 2
H), 2.98 (d, J = 6.2 Hz, 2 H), 3.35 (t, J = 7.3 Hz, 1 H), 3.69 (s, 6 H),
5.32 (dtt, J = 15.4, 7.3, 1.5 Hz, 1 H), 5.45 (dtt, J = 15.4, 6.2, 1.5 Hz,
1 H), 7.03 (dd, J = 7.5, 1.4 Hz, 2 H), 7.19 (tt, J = 7.5, 1.4 Hz, 1 H),
7.27 (td, J = 7.5, 1.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ (major) = 13.4, 20.9, 26.1, 31.9,
34.1, 52.0, 52.3, 125.5, 125.7, 127.7, 127.9, 128.5, 131.2, 134.5,
145.0, 169.2.
13C NMR (100 MHz, CDCl3): δ (minor) = 13.2, 17.0, 28.5, 31.8,
37.9, 52.0, 52.3, 125.4, 125.7, 127.9, 128.5, 130.7, 131.9, 134.4,
143.8, 169.2.
References
(1) (a) Jun, C.-H. Chem. Soc. Rev. 2004, 33, 610. (b) Rubin, M.;
Rubina, M.; Gevorgyan, V. Chem. Rev. 2007, 107, 3117.
(2) (a) Suginome, M.; Matsuda, T.; Yoshimoto, T.; Ito, Y.
Organometallics 2002, 21, 1537. (b) Zuo, G.; Louie, J.
Angew. Chem. Int. Ed. 2004, 43, 2277. (c) Zuo, G.; Louie, J.
J. Am. Chem. Soc. 2005, 127, 5798. (d) Liu, L.;
Montgomery, J. J. Am. Chem. Soc. 2006, 128, 5348.
(e) Ogoshi, S.; Nagata, M.; Kurosawa, H. J. Am. Chem. Soc.
2006, 128, 5350. (f) Bowman, R. K.; Jonson, J. S. Org. Lett.
2006, 8, 573. (g) Kimura, M.; Tamaru, Y. Top. Curr. Chem.
2007, 279, 173. (h) Ogata, K.; Atsuumi, Y.; Shimada, D.;
Fukuzawa, S.-i. Angew. Chem. Int. Ed. 2011, 50, 5896.
(3) (a) Kimura, M.; Ezoe, A.; Mori, M.; Tamaru, Y. J. Am.
Chem. Soc. 2005, 127, 201. (b) Kojima, K.; Kimura, M.;
Tamaru, Y. Chem. Commun. 2005, 4717. (c) Kimura, M.;
Kojima, K.; Tatsuyama, Y.; Tamaru, Y. J. Am. Chem. Soc.
2006, 128, 6332. (d) Kimura, M.; Mori, M.; Mukai, R.;
Kojima, K.; Tamaru, Y. Chem. Commun. 2006, 3813.
(e) Kojima, K.; Kimura, M.; Ueda, S.; Tamaru, Y.
Tetrahedron 2006, 62, 7512.
HRMS: m/z [M]+ calcd for C20H26O4: 330.1831; found (%): 371 ([M
+ 1]+, 23), 330.1832 (M+, 100), 315 (2), 301 (4), 299 (4).
Dimethyl 2-[(2E,5E)-5-Methyl-6-(trimethylsilyl)hepta-2,5-di-
enyl]malonate (3e)
Following typical procedure 2. Purification by flash chromatogra-
phy (hexane–EtOAc, 20:1) afforded 3e (4.26 g, 91%) as a colorless
oil; bp 120 °C/0.13 mbar.
(4) (a) Kimura, M.; Tatsuyama, Y.; Kojima, K.; Tamaru, Y.
Org. Lett. 2007, 9, 1871. (b) Kimura, M.; Togawa, M.;
Tatsuyama, Y.; Matsufuji, K. Tetrahedron Lett 2009, 50,
3982.
IR (neat): 2955 (s), 1740 (s), 1612 (w), 1437 (m), 1248 (m), 1155
(m), 972 (w), 856 (m), 837 (m), 756 (w), 689 cm–1 (w).
(5) Nakamura, T.; Mori, T.; Togawa, M.; Kimura, M.
Heterocyles 2012, 84, 339.
(6) (a) Ikeda, S.-i.; Cui, D.-M.; Sato, Y. J. Org. Chem. 1994, 59,
6877. (b) Ikeda, S.-i.; Miyashita, H.; Sato, Y.
1H NMR (400 MHz, CDCl3): δ = 0.12 (s, 9 H), 1.62 (d, J = 1.2 Hz,
3 H), 1.74 (q, J = 1.2 Hz, 3 H), 2.58 (ddd, J = 1.2, 6.8, 7.6 Hz, 2 H),
2.76 (d, J = 6.3 Hz, 2 H), 3.41 (t, J = 7.6 Hz, 1 H), 3.71 (s, 6 H), 5.34
(dt, J = 15.1, 6.8 Hz, 1 H), 5.46 (dtt, J = 15.1, 6.3, 1.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 0.40, 17.4, 22.9, 26.8, 31.9, 38.1,
52.0, 52.3, 125.5, 127.6, 130.6, 143.2, 169.2.
Organometallics 1998, 17, 4316. (c) Cui, D.-M.; Tsuzuki,
T.; Miyake, K.; Ikeda, S.-i.; Sato, Y. Tetrahedron 1998, 54,
1063.
HRMS: m/z [M]+ calcd for C16H28O4Si: 312.1757; found (%): 313
(7) Ikeda, S.; Obara, H.; Tsuchida, E.; Shirai, N.; Odashima, K.
Organometallics 2008, 27, 1645.
(M+, 22), 312.1743 (M+, 100), 297 (81).
(8) Mori, T.; Nakamura, T.; Kimura, M. Org. Lett. 2011, 13,
2266.
(9) Parsons, A. T.; Campbell, M. J.; Johnson, J. S. Org. Lett.
2008, 10, 2541.
Dimethyl 2-[(2E,5Z)-6,8-Diphenylocta-2,5-dien-7-ynyl]malo-
nate (4f)
Following typical procedure 2 using Ni(acac)2 (38.5 mg, 0.15
mmol), vinylcyclopropane (2.76 g, 15 mmol), phenylacetylene
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2333–2339