Transition-metal-catalyzed sequential cross-coupling of bis(iodozincio)methane and -ethane with two different organic halides

Article abstract of DOI:10.1002/chem.200500767

Bis(iodozincio)methane, prepared from diiodomethane and zinc, reacts with an organic halide in the presence of a transition-metal catalyst to give an iodozinciomethylenated compound; this then reacts with another organic halide to form a C-C bond. The overall process connects two electrophiles with one carbon atom. Bis(iodozincio)ethane can also undergo this transformation, yielding a new stereogenic center. The asymmetric induction of this stereogenic center was investigated by using a chiral palladium catalyst.

Full text of DOI:10.1002/chem.200500767

FULL PAPER
DOI: 10.1002/chem.200500767
Transition-Metal-Catalyzed Sequential Cross-Coupling of
Bis(iodozincio)methane and -ethane with Two Different Organic Halides
Hideaki Yoshino, Narihiro Toda, Masami Kobata, Katsumi Ukai, Koichiro Oshima,
Kiitiro Utimoto, and Seijiro Matsubara*[a]
Abstract: Bis(iodozincio)methane, prepared from diiodomethane and zinc, reacts
with an organic halide in the presence of a transition-metal catalyst to give an io-
À
dozinciomethylenated compound; this then reacts with another organic halide to
Keywords: C C bond formation ·
cross-coupling · gem-dizinc · nickel ·
palladium
À
form a C C bond. The overall process connects two electrophiles with one carbon
atom. Bis(iodozincio)ethane can also undergo this transformation, yielding a new
stereogenic center. The asymmetric induction of this stereogenic center was inves-
tigated by using a chiral palladium catalyst.
Introduction
These gem-dimetallic reagents have previously been used
for Wittig-type methylenation reactions of carbonyl com-
pounds.[4] In these reactions, the nucleophilic addition of a
gem-dimetallic reagent to a carbonyl group, followed by
elimination of a metal oxide, produced a Wittig-type olefina-
tion product. In addition to the Wittig-type reaction, other
synthetic applications of gem-dimetallic compounds were
discovered by Knochel and Normant in the 1980ꢀs.[5] For
their investigation, Knochel and Normant studied the reac-
tivity of gem-dimetal species that were prepared by Gaude-
mar/Normant coupling (Scheme 2). These gem-dimetal spe-
cies were treated with various electrophiles; however, cross-
coupling reactions were not studied well.
The cross-coupling reaction of an organometallic reagent
with an organic electrophile in the presence of a transition-
metal catalyst is one of the most important methods used to
construct molecular skeletons.[1] The reaction has been stud-
ied with a variety of organometallic reagents and electro-
À
philes, and has provided a general and efficient C C bond-
forming reaction. One can imagine that a sequential cross-
coupling reaction at one carbon atom would make this
transformation more useful, and thus provide a method for
the connection of two electrophiles with one carbon atom.
For this purpose, a gem-dimetallic reagent that contained
two carbon–metal bonds was prepared by our group
(Scheme 1).[2,3]
Scheme 2. Preparation of a gem-dimetal species by Gaudemar/Normant
coupling and its copper salt-mediated allylation.[5]
Scheme 1. General scheme for the sequential coupling reaction of a gem-
dimetallic reagent.
Since we reported a preparation method for bis(iodozin-
cio)methane (1) in 1998, we have investigated some specific
molecular transformations.[2a–c,6] A solution of the gem-
dizinc 1 in THF was obtained from the reaction of diiodo-
methane, zinc dust, and a catalytic amount of lead(ii) chlo-
ride. Detailed structural studies of 1 concluded that it is
monomeric in THF, although it is possible to form poly-
methylene zinc compounds, such as 2, by the Schlenk equi-
librium (Scheme 3).[7]
[a] H. Yoshino, Dr. N. Toda, M. Kobata, K. Ukai, Prof. Dr. K. Oshima,
Prof. Dr. K. Utimoto, Prof. Dr. S. Matsubara
Department of Material Chemistry
Graduate School of Engineering
Kyoto University, Kyoudai-katsura
Nishikyo, Kyoto 615–8510 (Japan)
Fax : (+81)75-383-2438
E-mail: matsubar@orgrxn.mbox.media.kyoto-u.ac.jp
Chem. Eur. J. 2006, 12, 721 – 726
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
721

chloride. In a previous investigation by our group, the struc-
ture of 1 was studied intensively by X-ray and neutron scat-
tering,[12] and it was shown that the contribution of the
Schlenk equilibrium was not significant, provided the con-
centration of 1 in THF was less than 0.5m and the tempera-
ture less than that of room temperature. This means that
when 1 is prepared as a solution in THF, it can keep its ho-
mogeneity as a monomeric form; this is crucial if the se-
quential coupling reaction is to work effectively.
Scheme 3. Preparation of bis(iodozincio)methane (1) and its Schlenk
equilibrium.[7]
Organomonozinc reagents have often been utilized for
transition-metal-catalyzed cross-coupling reactions;[13] there-
fore, we decided to examine a palladium(0)-catalyzed cross-
coupling reaction (Table 1). Four molar equivalents of vari-
ous phosphines 3 and Pd2dba3·CHCl3 were mixed in THF
under an atmosphere of argon to prepare the palladium cat-
alyst (Pd0/PR3 1:2).[14] The reactions were carried out by
using 2.5 mol% of the palladium catalyst, and were
quenched with 1m DCl/D2O (DCl=deuterium chloride) to
give compounds 5. By alternating the selection of the phos-
phine ligand, the yield of the coupling product was in-
creased, with tris(2-furyl)phosphine (3c) and tris[3,5-bis(tri-
fluoromethyl)]phosphine (3d) producing excellent results.[15]
For the next step in our study, an organic halide was used
as the second electrophile (versus DCl/D2O) in these reac-
tions (Scheme 5). Thus, organomonozinc species 4a, ob-
tained from the reaction of 1 with cinnamyl chloride in situ,
was treated with allyl bromide and benzoyl chloride. The ex-
isting palladium catalyst was effective for the second cross-
coupling reaction, and the sequential coupling products 6
The treatment of a solution of 1 in [D8]THF with one
molar equivalent of deuterium oxide in an NMR tube ef-
fected sequential deuteration (Scheme 4). From this result,
Scheme 4. Sequential deuteration of bis(iodozincio)methane (1).
À
we deduced that the reactivity of the C Zn bond in 1 is sig-
nificantly greater than that in methylzinc iodide when these
species are reacting with water or iodine. Thus, we conclud-
À
ed that it was possible for two gem-C Zn bonds to be used
individually and sequentially for cross-coupling reactions.
Our results for the cross-coupling reactions of the organo-
metallic reagent 1 with organic halides are described herein.
Results and Discussion
Table 1. Palladium-catalyzed cross-coupling of 1 with allylic chloride.[a]
Treatment of diiodomethane
with zinc powder in the pres-
ence of lead(ii) chloride[10] in
anhydrous THF produced bis-
(iodozincio)methane (1) in
50% yield (0.5m solution in
Ph3P 3b
(C2H5O)3P 3e
THF,
as
determined
by
1H NMR spectroscopic analysis,
with 2,2,4,4-tetramethylbutane
as an internal standard) by
means of a slightly exothermic
reaction.[11] Takai and Utimoto
have shown that only a small
amount of lead(ii) chloride is
required for it to work effective-
ly as a catalyst.[10] Indeed, as
little as 0.05 mol% lead(ii) chlo-
ride/zinc is required for the re-
action to be effective enough.
Lead metal, lead(ii) bromide,
and lead(ii) acetate are also ef-
fective catalysts for this reac-
tion. When pyrometallurgy zinc,
which contains approximately
0.04–0.07% lead, was used it
5a (R=Ph)
5b (R=nC11H23)
<1%
<1%
16%
<1%
88%
82%
97%
91%
14%
<1%
[a] 2a=cinnamyl chloride and 2b=1-chloro-2-tetradodecene.
was not necessary to add lead(ii) Scheme 5. Sequential cross-coupling of 1 with an allylic halide and another electrophile.
722
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Chem. Eur. J. 2006, 12, 721 – 726

Cross-Coupling Reactions
FULL PAPER
listed in Table 1 were examined,
none of the desired cross-cou-
pling product was obtained.
NiCl2dppp
(dppp=1,3-diphe-
nylphosphinopropane), howev-
er, was an effective catalyst for
this reaction, and the resulting
allyl zinc 13 formed in situ was
treated with allyl bromide to
give the diene 14. Alternatively,
treatment of 13 with isopropyl-
aldehyde produced the homo-
allylic alcohol 15, a product of
Scheme 6. Sequential cross-coupling of 1 with an aryl halide and allyl bromide.
À
C C bond formation at the
g-position (Scheme 7).
Treatment
of 1,1-diiodo-
ethane with zinc dust in the
presence of a catalytic amount
of lead(II) chloride produced
the gem-dizinc species 16. Se-
quential coupling of 16 with
cinnamyl chloride and allyl bro-
mide produced 18 (Scheme 8).
The sequential coupling reac-
tions described above, should
have proceeded by the normal
cross-coupling mechanism; that
is, oxidative insertion of a tran-
sition-metal catalyst into the
first organic halide to give
Scheme 7. Sequential cross-coupling of 1 with b-bromostyrene and allyl bromide or aldehyde.
À À
R M X, followed by a trans-
metallation reaction with the
gem-dizinc reagent, and then
reductive elimination to afford
the iodozincioalkylated cou-
pling product. The product
from this sequence will become
a reactant for other cross-cou-
pling reactions (Scheme 9).
Scheme 8. Sequential cross-coupling of 1,1-bis(iodozincio)ethane (16) with cinnamyl chloride and allyl
bromide.
and 7 were obtained. However, when propargyl bromide
was used as the second organic halide, the addition of a
copper salt became necessary.
The coupling reactions of bis(iodozincio)methane (1) with
different aryl iodides proceeded effectively in the presence
of the palladium catalyst, prepared from Pd(dba)3·CHCl3
and
tris[bis(trifluoromethyl)phenyl]phosphine
(3d),
(Scheme 6) to produce benzylzinc intermediates, which were
subsequently treated with allyl bromide. For these reactions,
the second cross-coupling reaction would not proceed with-
out the addition of additional copper salt.
Scheme 9. Proposed mechanism for the sequential coupling.
For the sequential coupling reaction of 1 with a bromoal-
kene, such as b-bromostyrene (12), the first coupling reac-
tion affords an allylic zinc intermediate. Following the pro-
cedure illustrated in Schemes 5 and 6, b-bromostyrene (12)
was treated with bis(iodozincio)methane (1) in the presence
of various palladium catalysts. Although all of the ligands
For compound 16, sequential coupling with two different
electrophiles resulted in the formation of an asymmetric
carbon. If the enantiotopic iodozincio groups in gem-di-
zincioethane (16) are selectively transmetallated with a pal-
ladium species that contains chiral ligands, then the follow-
Chem. Eur. J. 2006, 12, 721 – 726
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www.chemeurj.org
723

S. Matsubara et al.
Table 2. Enantioselective preparation of configurationally stable organozinc compound 21.[a]
Conclusion
The cross-coupling reaction of
bis(iodozincio)methane can be
performed stepwise and se-
quentially. This method has
provided a route for the combi-
nation two electrophiles with
one carbon atom. Bis(iodozin-
cio)methane is monomeric in
THF with a high homogeneity,
a crucial feature for these se-
quential coupling reactions.
However, instead of bis(iodo-
zincio)methane, one might also
try Nysted reagent, prepared
from dibromomethane and zinc
in the presence of a lead cata-
lyst, for these reactions (com-
mercially available from Al-
drich). Unfortunately, the use
of Nysted reagent (polymethy-
lene zinc) was not successful for
our sequential coupling reac-
tions.
Entry
X in 19
Ligand
Yield of 22 [%]
ee [%][b]
R/S
1
2
3
4
5
6
7
8
9
Cl
OAc
OBz
OCO2Me
OCO2iBu
OCO2iBu
OCO2iBu
OCO2iBu
OCO2iBu
20a[9a]
20a
20a
81
78
68
69
70
10
22
31
32
33
32
–
R
R
R
R
R
R
–
20a
20a
20b[9b]
20c[9c]
20d[9c]
20e[9d]
73
<1
<1
40
–
13
–
S
[a] Compound 16 (1.0 mmol), Pd2dba3·CHCl3 (0.25 mmol), 20 (0.1 mmol), and 19 (1.0 mmol) were used for the
preparation of 21. This compound was treated with CuCN·2LiCl (1.2 mmol) at À308C and then reacted with
propargyl bromide to give 22. [b] Enantiomeric purity (ee=enantiomeric excess) was determined by GPLC
(Chrompack CP-Chiralsil-Dex CB, 25 mꢂ0.25 mm, 408C, 60 min; 28CminÀ1 to 1308C; 1308C, 130 min for (S)-
22 and 140 min for (R)-22).
ing reductive elimination should afford secondary organo-
zinc species 21 with enantiomeric excess (Table 2).[16] The
copper-mediated reaction with organozinc reagent proceeds
Experimental Section
stereospecifically, thus the enantiomeric excess in 21 should
be reflected in that of 22.[17,18] Unfortunately, only very low
values of asymmetric induction were realized, despite the in-
vestigation of many different types of phosphine ligand.
However, a chiral monophosphine ligand carrying a biphen-
yl group (developed by Hayashi) and a chiral binol based
phosphite ligand (developed by Feringa), did produce some
enantiomeric excess.[19] The absolute configuration of 22 was
determined by comparison with an authentic sample, pre-
pared from (À)-b-citronellene (Scheme 10).
Dehydrated, stabilizer free THF was purchased from Kanto Chemical.
[D8]THF was distilled over benzophenone-ketyl. 1,3-dimethylimidazolid-
din-2-one (DMI) was distilled over calcium hydride. The zinc powder
(Wako) was washed with 10% HCl before use, according to the reported
procedure. 1,1-diiodoethane was prepared according to the literature pro-
cedure.[20] Chromatographic purification of products was accomplished by
using forced-flow chromatography on silica gel (supplied by Kanto
Chemical, 60 N, spherical, neutral). 1H and 13C NMR spectra were re-
corded on a Varian Gemini-2000 (300 and 75 MHz, respectively), and
were internally referenced to residual proton solvent signals. For the
1H NMR spectra, s=singlet, d=doublet, t=triplet, q=quartet, and m=
multiplet). HRMS were generated by a JEOL Mstation 700 spectrome-
ter.
Preparation of bis(iodozincio)methane (1): A mixture of zinc powder
(150 mmol) and diiodomethane (1.0 mmol) in THF (2 mL) was sonicated
for 1 h. After this time, additional diiodomethane (49 mmol) in THF
(48 mL) was slowly added at 08C, and the mixture was then stirred for a
further 1 h at 258C. The integral of the a-proton peak relative to the in-
ternal standard in the 1H NMR spectrum was used to measure the con-
centration factor. 1H NMR (300 MHz, [D8]THF): d=À1.10 ppm (brs,
2H); 13C NMR (75 MHz, [D8]THF): d=À14.3 ppm.
General procedure for the palladium-catalyzed cross-coupling of 1 with
allylic chloride: Allylic chloride (1.0 mmol in THF, 1.0 mL) and 1 (0.5m
solution in THF, 2.0 mL, 1.0 mmol) were added to
a solution of
[Pd2(dba)3]·CHCl3 (26 mg, 0.025 mmol) and phosphine (0.1 mmol) in
THF (1.0 mL), and the mixture was stirred at room temperature for
30 min. After this time, DCl (2.0 mL, 1m solution in D2O) was added at
08C, and the resulting mixture was stirred for a further 5 min. Once the
reaction was complete, the mixture was extracted with ether. The organic
layers were then combined, washed with brine, and dried over Na2SO4.
The product was isolated by silica-gel column chromatography.
4-Deuterio-1-phenyl-1-butene (5a): 1H NMR (300 MHz, CDCl3): d=
Scheme 10. Preparation of optically active (R)-22.
7.41–7.23 (m, 5H), 6.38 (d, J=16.2 Hz, 1H), 6.27 (dt, J=6.0, 16.2 Hz,
724
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Chem. Eur. J. 2006, 12, 721 – 726

Cross-Coupling Reactions
FULL PAPER
2H), 2.27–2.02 (m, 2H), 1.09 ppm (tt, J=2.1, 7.2 Hz, 2H); 13C NMR
(75 MHz, CDCl3): d=138.21, 132.91, 129.06, 128.74, 127.03, 126.19, 26.51,
13.92 ppm (t, J=19.2 Hz); HRMS: calcd for C10H11D: 133.1001 [M]+;
found: 133.0999.
1-Deuterio-3-pentadecene (5b): 1H NMR (300 MHz, CDCl3): d=5.47–
5.36 (m, 2H), 2.00–1.94 (m, 4H), 1.38–1.26 (m, 18H), 0.94 (tt, J=2.0,
7.5 Hz, 2H), 0.88 ppm (t, J=6.5 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d=132.08, 129.65, 34.08, 32.84, 32.18, 29.94, 29.92, 29.90, 29.80, 29.61,
29.45, 25.78, 22.95, 14.38, 13.97 ppm (t, J=19.5 Hz); HRMS: calcd for
C15H29D: 214.2410 [M]+; found: 211.2401.
4.98 (d, J=10.2 Hz, 1H), 2.72 (t, J=7.8 Hz, 2H), 2.38 ppm (td, J=7.8,
6.6 Hz, 2H).
4-(o-Tolyl)-1-butene (10b):[23] 1H NMR (300 MHz, CDCl3): d=7.17–7.08
(m, 4H), 5.88 (tdd, J=6.6, 10.2, 17.3 Hz, 1H), 5.05 (d, J=17.3 Hz, 1H),
4.98 (d, J=10.2 Hz, 1H), 2.72 (t, J=7.8 Hz, 2H), 2.37 (td, J=7.8, 6.6 Hz,
2H), 2.31 ppm (s, 3H).
4-(4-Bromophenyl)-1-butene (10c): 1H NMR (300 MHz, CDCl3): d=7.37
(d, J=8.2 Hz, 2H), 7.06 (d, J=8.2 Hz, 2H), 5.80 (tdd, J=6.6, 10.2,
17.3 Hz, 1H), 5.05 (d, J=17.3 Hz, 1H), 4.98 (d, J=10.2 Hz, 1H), 2.67 (t,
J=8.2 Hz, 2H), 2.35 ppm (m, 2H).
1-Phenyl-1,6-heptadiene (6):[21] Cinnamyl chloride (1.0 mmol in THF,
1.0 mL) and 1 (0.5m solution in THF, 2 mL, 1.0 mmol) were added to a
solution of [Pd2(dba)3]·CHCl3 (26 mg, 0.025 mmol) and 3c (0.1 mmol) in
THF (1.0 mL), and the mixture was stirred at room temperature for
30 min. After this time, allyl bromide (1.5 mmol in THF 1.0 mL) was
added to the mixture at room temperature. The resulting mixture was
stirred for 2 h, and was then poured into saturated aqueous NH4Cl solu-
tion and extracted with ether. The combined organic layers were washed
with brine and dried over Na2SO4. The product produced was isolated by
silica-gel column chromatography. 1H NMR (300 MHz, CDCl3): d=7.38–
7.21 (m, 5H), 6.37 (d, J=16.2 Hz, 1H), 6.20 (dt, J=7.5, 16.2 Hz, 1H),
5.84 (ddt, J=6.6, 10.2, 17.1 Hz, 1H), 5.02 (d, J=17.1 Hz, 1H), 4.96 (d,
J=10.2 Hz, 1H), 2.24 (dt, J=7.2, 7.5 Hz, 2H), 2.10 (dt, J=6.6, 7.2 Hz,
2H), 1.56 ppm (tt, J=7.2, 7.2 Hz, 2H).
General procedure for the nickel-catalyzed cross-coupling of 1 with vinyl
halides: b-Bromostylene (1.0 mmol in THF, 1.0 mL) and 1 (0.5m solution
in THF, 2 mL, 1.0 mmol) were added to a suspension of NiCl2dppp
(27 mg, 0.05 mmol) in THF (2.0 mL), and the mixture was stirred for
30 min at room temperature. After this time, a solution of the electro-
phile (1.5 mmol) in THF (1.0 mL) was added, and the reaction mixture
was then stirred for a further 2 h, before being poured into a solution of
saturated aqueous NH4Cl and extracted with ether. The combined organ-
ic layers were washed with brine and dried over Na2SO4. The product
was isolated by silica-gel column chromatography.
1-Phenyl-1,5-hexadiene (14):[24] 1H NMR (300 MHz, CDCl3): d=7.37–
7.16 (m, 5H), 6.40 (d, J=16.2 Hz, 1H), 6.24 (dt, J=6.3, 16.2 Hz, 1H),
5.84 (ddt, J=6.6, 10.2, 17.1 Hz, 1H), 5.00 (d, J=17.1 Hz, 1H), 4.98 (d,
J=10.2 Hz, 1H), 2.38–2.20 ppm (m, 4H).
1,5-Diphenyl-4-penten-1-one (7): Cinnamyl chloride (1.0 mmol in THF,
1.0 mL) and 1 (0.5m solution in THF, 2 mL, 1.0 mmol) were added to a
solution of [Pd2(dba)3]·CHCl3 (26 mg, 0.025 mmol) and 3c (23 mg,
0.1 mmol) in THF (2.0 mL), and the resulting mixture was stirred at
room temperature for 30 min. After this time, DMI (2.0 mL) and benzoyl
chloride (140 mg, 1.0 mmol) were added at 08C, and the mixture was stir-
red for a further 2 h, before being poured into a solution of saturated
aqueous NH4Cl and extracted with ether. The combined organic layers
were washed with brine and dried over Na2SO4. The product was isolated
by silica-gel column chromatography. 1H NMR (300 MHz, CDCl3): d=
8.02 (d, J=7.2 Hz, 2H), 7.20–7.52 (m, 8H), 6.48 (d, J=15.6 Hz, 1H), 6.27
(dt, J=6.8, 15.6 Hz, 1H), 3.15 (t, J=7.5 Hz, 2H), 2.64–2.70 ppm (m, 2H).
2-Methyl-4-phenyl-5-hexen-3-ol (15):[25] The product was obtained as a
diastereomeric mixture in a ratio of anti/syn 93:7. 1H NMR (300 MHz,
CDCl3): d=7.33–7.30 (m, 2H), 7.23–7.20 (m, 3H), 6.12 (ddd, J=8.0, 8.5,
16.5 Hz, 0.93H), 6.01 (ddd, J=8.0, 8.5, 16.5 Hz, 0.07H), 5.22–5.18 (m,
1.86H), 5.12–5.02 (m, 0.14H), 3.8–3.7 (m, 0.07H), 3.60 (ddd, J=3.0, 8.0,
8.5 Hz, 0.93H), 3.42 (dd, J=8.0, 8.0 Hz, 0.07H), 3.38 (dd, J=8.0, 8.0 Hz,
0.93H), 1.71 (d, J=3.0 Hz, 1H), 1.57–1.51 (m, 1H), 0.89 ppm (d, J=
6.5 Hz, 6H).
Preparation of 1,1-bis(iodozinscio)ethane (16): A mixture of zinc powder
(60 mmol) and 1,1-diiodoethane (1.0 mmol) in THF (2 mL) was sonicated
for 1 h. After this time, additional 1,1-diiodoethane (19 mmol) in THF
(18 mL) was added slowly at 08C, and the resulting mixture was stirred
for 1 h at 258C. The integral of the a-proton peak relative to the internal
standard in the 1H NMR spectrum was used to measure the concentra-
tion factor. 1H NMR (300 MHz, [D8]THF): d=1.45 (d, J=7.8 Hz, 3H),
À0.08 (q, J=7.8 Hz, 1H); 13C NMR (75 MHz, [D8]THF): d=12.0,
4.2 ppm.
7-Phenyl-1,2,6-heptatriene (8): Cinnamyl chloride (1.0 mmol in THF,
1.0 mL) and 1 (0.5m solution in THF, 2 mL, 1.0 mmol) were added to a
solution of [Pd2(dba)3]·CHCl3 (26 mg, 0.025 mmol) and 3c (23 mg,
0.1 mmol) in THF (1.0 mL), and the resulting mixture was stirred at
room temperature for 30 min. After this time, CuCN·2LiCl (1m solution
in THF, 1.2 mL) was added at À308C, and the mixture stirred for a fur-
ther 5 min. Propargyl bromide (1.5 mmol) was then added at À788C.
This mixture was warmed to room temperature and stirred for 1 h,
before being poured into a solution of saturated aqueous NH4Cl and ex-
tracted with ether. The combined organic layers were washed with brine
and dried over Na2SO4. The product was isolated by silica-gel column
chromatography. 1H NMR (300 MHz, CDCl3): d=7.36–7.18 (m, 5H),
6.43 (d, J=15.9 Hz, 1H), 6.24 (dt, J=6.6, 15.9 Hz, 1H), 5.17 (dt, J=6.6,
12.9 Hz, 1H), 4.70 (dt, J=3.3, 6.6 Hz, 2H), 2.35 (dt, J=6.6, 8.1 Hz, 2H),
2.24–2.14 ppm (m, 2H); 13C NMR (75 MHz, CDCl3): d=208.70, 138.00,
130.75, 130.19, 128.76, 127.19, 126.25, 98.73, 75.48, 33.01, 28.56 ppm;
HRMS: calcd for C13H14: 170.1096 [M]+; found: 170.1089.
General procedure for the sequential cross-coupling of 16 with cinnnamyl
chloride and allyl bromide: Cinnamyl chloride (1.0 mmol in THF 1.0 mL)
and 16 (0.5m solution in THF, 2 mL, 1.0 mmol) were added to a solution
of [Pd2(dba)3]·CHCl3 (26 mg, 0.025 mmol) and 3c (23 mg, 0.1 mmol) in
THF 1.0 mL, and the mixture was stirred at room temperature for
30 min. After this time, allyl bromide (1.5 mmol in THF, 1.0 mL) was
added at room temperature and the resulting mixture was stirred for 2 h.
The mixture was then poured into a solution of saturated aqueous NH4Cl
and extracted with ether. The combined organic layers were washed with
brine and dried over Na2SO4. Finally, the product was isolated by silica-
gel column chromatography.
4-Methyl-1-phenyl-1,6-heptadiene (18): 1H NMR (300 MHz, CDCl3): d=
7.37–7.19 (m, 5H), 6.39 (d, J=16.0 Hz, 1H), 6.22 (dt, J=7.5, 16.0 Hz,
1H), 5.82 (ddt, J=7.0, 8.0, 16.5 Hz, 1H), 5.04 (d, J=16.5 Hz, 1H), 5.02
(d, J=8.0 Hz, 1H), 2.30–2.22 (m, 1H), 2.18–2.12 (m, 1H), 2.10–2.04 (m,
1H), 1.98–1.93 (m, 1H), 1.74–1.65 (m, 1H), 0.95 ppm (d, J=6.8 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=138.08, 137.65, 131.39, 129.66, 128.74,
127.09, 126.19, 116.12, 41.22, 40.27, 33.53, 19.65 ppm. HRMS: calcd for
C14H18: 186.1400 [M]+; found: 186.1409.
4-Methyl-7-phenyl-1,2,6-heptatriene (22): 1H NMR (300 MHz, CDCl3):
d=7.37–7.19 (m, 5H), 6.39 (d, J=16.0 Hz, 1H), 6.22 (dt, J=7.5, 16.0 Hz,
1H), 5.17 (dt, J=6.6, 8.1 Hz, 1H), 4.74 (d, J=6.6 Hz, 1H), 4.73 (d, J=
6.6 Hz, 1H), 2.37–2.29 (m, 2H), 2.25–2.19 (m, 1H), 1.07 ppm (d, J=
6.5 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=207.74, 138.00, 131.67,
129.11, 128.74, 127.18, 126.25, 95.81, 76.18, 40.76, 33.16, 20.09 ppm.
HRMS: calcd for C14H16: 184.1248 [M]+; found: 184.1252. Enantiomeric
General procedure for the sequential cross-coupling of 1 with aryl halide
and allyl bromide: Aryl iodide (1.0 mmol in THF, 1.0 mL) and 1 (0.5m
solution in THF, 2 mL, 1.0 mmol) were added to
a solution of
[Pd2(dba)3]·CHCl3 (26 mg, 0.025 mmol) and 3d (67 mg, 0.1 mmol) in
THF (1.0 mL), and the mixture was stirred at room temperature for
30 min. After this time, CuCN·2LiCl (1m solution in THF, 1.2 mL) was
added to the mixture at À308C, and it was stirred for a further 5 min.
Propargyl bromide (1.5 mmol) was then added at À788C. This mixture
was warmed to room temperature and stirred for 1 h, before being
poured into a solution of saturated aqueous NH4Cl and extracted with
ether. The combined organic layers were washed with brine and dried
over Na2SO4. The product was isolated by silica-gel column chromatogra-
phy.
4-Phenyl-1-butene (10a):[22] 1H NMR (300 MHz, CDCl3): d=7.31–7.16
(m, 5H), 5.87 (ddt, J=6.6, 10.2, 17.3 Hz, 1H), 5.05 (d, J=17.3 Hz, 1H),
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S. Matsubara et al.
purity was determined by GPLC (Chrompack CP-Chiralsil-Dex CB,
25 mꢂ0.25 mm, 408C, 60 min; 28CminÀ1 to 1308C; 1308C, 130 min for
(S)-7 and 140 min for (R)-7).
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Acknowledgement
This work was financially supported by the Japanese Ministry of Educa-
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Pharmaceutical, Takahashi Industrial, and the Economical Research
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Received: July 4, 2005
Published online: October 13, 2005
726
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Chem. Eur. J. 2006, 12, 721 – 726