Functionalized arylzinc compounds in ethereal solvent: Direct synthesis from aryl iodides and zinc powder and application to Pd-catalyzed reaction with allylic halides

Article abstract of DOI:10.1021/jo026746s

Arylzinc compounds, ArZnX, were conveniently prepared in high yields by the reaction of zinc powder with aryl iodides, which contain electron-withdrawing groups such as CO₂CH₃, CN, Br, or CF₃ at the ortho-, meta- or para-position, or electron-donating groups such as CH₃, OCH₃, or H, at 70 °C in THF, at 100 °C, or at 130 °C in diglyme, respectively. Pd(dba)2 exhibited an outstanding efficient catalytic effect for the cross-coupling of these ethereal solutions of ArZnX with allylic halides to afford a variety of functionalized allylbenzenes in high yields; the reactions were mostly carried out at 0 °C for 5-30 min in the presence of 5 mol % of catalyst. The conversion of the aryl iodides to allylbenzenes via two reactions could be accomplished in one pot.

Full text of DOI:10.1021/jo026746s

F u n ction a lized Ar ylzin c Com p ou n d s in Eth er ea l Solven t: Dir ect
Syn th esis fr om Ar yl Iod id es a n d Zin c P ow d er a n d Ap p lica tion to
P d -Ca ta lyzed Rea ction w ith Allylic Ha lid es
Ryo Ikegami, Akiko Koresawa, Takanori Shibata, and Kentaro Takagi*
Department of Chemistry, Faculty of Science, Okayama Univesity, Tsushima, Okayama 700-8530, J apan
takagi@cc.okayama-u.ac.jp
Received November 21, 2002
Arylzinc compounds, ArZnX, were conveniently prepared in high yields by the reaction of zinc powder
with aryl iodides, which contain electron-withdrawing groups such as CO
the ortho-, meta- or para-position, or electron-donating groups such as CH
in THF, at 100 °C, or at 130 °C in diglyme, respectively. Pd(dba) exhibited an outstanding efficient
2
CH
3
, CN, Br, or CF
3
at
3
, OCH
3
, or H, at 70 °C
2
catalytic effect for the cross-coupling of these ethereal solutions of ArZnX with allylic halides to
afford a variety of functionalized allylbenzenes in high yields; the reactions were mostly carried
out at 0 °C for 5-30 min in the presence of 5 mol % of catalyst. The conversion of the aryl iodides
to allylbenzenes via two reactions could be accomplished in one pot.
In tr od u ction
-
As a reactive and chemoselective Ar -supplying re-
agent, arylzinc compounds, ArZnX, which have been
generally prepared by the metathesis of ArLi or ArMgX
1
and ZnX
2
in THF (Figure 1, path A), are extensively
utilized in organic synthesis. By comparison, the recently
developed synthetic method for ArZnX of treating ArX
with Zn powder in polar solvents such as HMPA, DMF,
DMSO, or TMU is far more convenient and atom eco-
2
nomic (Figure 1, path B). Moreover, a variety of reactive
functional groups such as esters, nitriles, ketones, or
halogens (Br and Cl) in ArX does not interfere with the
oxidative addition of C-X bonds to Zn powder. Therefore,
functionalized compounds are readily available based on
this method. The obtained ArZnX has been successfully
utilized in Cu(I)- or Cr(III)-mediated and Pd(0)-catalyzed
reactions with various electrophilic reagents such as acyl
halides, allylic halides, R,â-unsaturated ketones, alde-
hydes, or aryl halides, sometimes in place of the conven-
F IGURE 1. Synthesis of arylzinc compounds.
appropriate not only for the preparation but also for the
utilization of ArZnX. In this context, the aforementioned
polar solvents might limit the utility of ArZnX, since
organometallic reactions are often carried out in less
polar solvents such as THF. At present, there exist
several sophisticated methods of synthesizing func-
tionalized ArZnX in THF (Figure 1, path C), how-
ever, it is desirable to disclose the most convenient and
not chemical wasting synthetic method of these com-
tional ArZnX in THF.2,3 Here it is noted that, because of
the lability of the organozinc compounds to moisture, the
solution containing ArZnX is used in subsequent reac-
tions as obtained. Consequently, a given solvent must be
4
,5
(
1) (a) Negishi, E. In Organometallics in Organic Synthesis; J ohn
Wiley & Sons: New York, 1980; p 91. (b) Erdik, E. Organozinc Reagents
in Organic Synthesis; CRC Press: Boca Raton, FL, 1996.
(4) (a) Zhu, L.; Wehmeyer, R. M.; Rieke, R. D. J . Org. Chem. 1991,
56, 1445. (b) Tucker, C. E.; Majid, T. N.; Knochel, P. J . Am. Chem.
Soc. 1992, 114, 3983. (c) Uchiyama, M.; Koike, M.; Kameda, M.; Kondo,
Y.; Sakamoto, T. J . Am. Chem. Soc. 1996, 118, 8733. (d) Kondo, Y.;
Takazawa, N.; Yamazaki, C.; Sakamoto, T. J . Org. Chem. 1994, 59,
4717. (e) Studemann, T.; Gupta, V.; Engman, L.; Knochel, P. Tetra-
hedron Lett. 1997, 38, 1005. (f) Furstner, A.; Singer, R.; Knochel, P.
Tetrahedron Lett. 1994, 35, 1047. See also: (g) Sibille, S.; Ratovelo-
manana, V.; Perichon, J . J . Chem. Soc., Chem. Commun. 1992, 283.
(h) Gosmini, C.; Rollin, Y.; Nedelec, J . Y.; Perichon, J . J . Org. Chem.
2000, 65, 6024.
(2) (a) Takagi, K.; Hayama, N.; Inokawa, S. Bull. Chem. Soc. J pn.
1
980, 53, 3691. (b) Takagi, K. Chem. Lett. 1993, 469. (c) Takagi, K.;
Shimoishi, Y.; Sasaki, K. Chem. Lett. 1994, 2055. (d) Amano, M.; Saiga,
A.; Ikegami, R.; Ogata, T.; Takagi, K. Tetrahedron Lett. 1998, 39, 8667.
(
e) Majid, T. N.; Knochel, P. Tetrahedron Lett. 1990, 31, 4413.
(3) (a) Ogawa, Y.; Saiga, A.; Mori, M.; Shibata, T.; Takagi, K. J . Org.
Chem. 2000, 65, 1031. (b) Ogawa, Y.; Mori, M.; Saiga, A.; Takagi, K.
Chem. Lett. 1996, 1069. (c) Saiga, A.; Hossain, K. M.; Takagi, K.
Tetrahedron Lett. 2000, 41, 4629. (d) Hossain, K. M.; Shibata, T.;
Takagi, K. Synlett 2000, 1137. (e) Hossain, K. M.; Kameyama, T.;
Shibata, T.; Takagi, K. Bull. Chem. Soc. J pn. 2001, 74, 2415.
(5) Several THF solutions of functionalized ArZnX are commercially
available from Sigma-Aldrich.
1
0.1021/jo026746s CCC: $25.00 © 2003 American Chemical Society
Published on Web 02/25/2003
J . Org. Chem. 2003, 68, 2195-2199
2195

Ikegami et al.
TABLE 1. Syn th esis of Ar ylzin c Com p ou n d s in Eth er ea l
(bp 215 °C), less volatile ethereal solvents, to conduct the
preparation in ordinary glassware and render the pro-
cedure simple and useful from a practical viewpoint. First
of all, diglyme and triglyme were equally effective as THF
for the reaction of the reactive ArI (Runs 1, 3, 7, and 8).
It was ascertained that the increase in the reaction
temperature by 30 °C (bath temperature 100 °C) or 60
a
Solven t
°
C (bath temperature 130 °C) was sufficient to enhance
the reactivity of the electron-poor ArI (ones containing
EWG such as CO CH , CO , Cl, or Br at the meta-
Run
R
1
solvent
temp, °C
2
yield, %b
1
2
3
4
5
6
7
8
9
2-CO2CH3
2-CN
1a
1b
1c
1d
1e
THF
THF
THF
THE
THF
THF
diglyme
triglyme
diglyme
diglyme
diglyme
diglyme
diglyme
diglyme
diglyme
diglyme
diglyme
70
70
70
70
70
70
70
70
100
100
100
100
100
100
130
130
130
130
160
180
180
180
2a
2b
2c
2d
2e
2f
2c
2a
2e
2f
2g
2h
2i
2j
2j
2k
2l
2m
2i
87
94
95
2
3
2 2 5
C H
c
or para-position) (Runs 9-13) or electron-rich ArI (ones
containing EDG) (Runs 15-18) in diglyme, resulting in
the completion of the reactions in 24 h, respectively. From
these reactions, the desired products were obtained in
good yields. Fortunately, further elevation of the reaction
temperature merely shortened the reaction time, without
decreasing the yield due to the thermal robustness of
ArZnX in ethereal solvents (Runs 19-22). For example,
a raise in the reaction temperature by 110 °C from 70
2-Br
2-CF3
3-CO2CH3
4-CO2C2H5 1f
70
20
<5
82
86
84
89
83
2-Br
1c
1a
1e
2-CO2CH3
3-CO2CH3
4-CO2C2H5 1f
1
1
1
1
1
1
1
1
1
1
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
4-Cl
4-Br
3-Cl
1g
1h
1i
1j
1j
c
87
84
51
87
87
86
83
81
78
78
83
°
C shortened the reaction time from 24 h in THF to 10
4-CH3
min in triglyme, retaining a good yield (87 or 78%) for
1a (Runs 1 and 21). The bromo-substituent in ArI was
retained intact during the reaction (Runs 3 and 12), but
at the higher temperature of around 200 °C (in triglyme),
the reaction of bromobenzene with Zn powder took place.
However, PhZnX was obtained only in low yield (6%).
Rea ction of a n Eth er ea l Solu tion of Ar Zn X w ith
Allylic Ha lid es. Next, we investigated the utility of our
ethereal solution of ArZnX for organic synthesis, taking
up the cross-coupling with allylic electrophiles leading
to allylbenzenes as a probe. Although the efficiency of
Pd or Ni catalysis for the reaction of ordinary ArZnX (Ar
4-OCH3
2-OCH3
H
1k
1l
1m diglyme
d
e
f
3-Cl
1i
1i
1a
1j
diglyme
triglyme
triglyme
triglyme
2i
2a
2j
2-CO2CH3
4-CH3
g
a
Molar ratio: 1/Zn/Me3SiCl ) 1/2/0.03. Conv.: >97% except for
b
Runs 5 (25%), 6 (8%), and 14 (68%). GLC yield of reproduced
ArI, after I2 treatment of reaction mixture (see Experimental
c
d
Section). C-Br bond was retained intact. Reaction time: 30 min.
e
f
g
Reaction time: 15 min. Reaction time: 10 min. Reaction time:
.5 h.
1
)
phenyl, p-tolyl, or 1-naphthyl) has been known for two
9
,10
decades,
the functionalized ones have been rarely
applied to the reaction.1
b,11
pounds in weakly polar solvents. Therefore, we investi-
gated the direct reaction between ArX and Zn powder
using ethereal solvents such as THF.
At first, the solution composed of PhZnI, allyl acetate
3 4
(1.1 equiv), and Pd(PPh ) (5 mol %) in diglyme was
stirred at room temperature for 6 h under nitrogen.
9
Under very typical conditions, allylbenzene was obtained
Resu lts a n d Discu ssion
in 78% yield along with a small amount of biphenyl (7%),
which showed that our ArZnX possessed reactivity
similar to the conventional ones prepared from ArLi or
Syn th esis of Ar Zn X in Eth er ea l Solven t. The
reactions of various aryl iodides (ArI) 1 with Zn powder
9
(2 equiv) were carried out at 70 °C (bath temperature)
ArMgX and ZnX in THF (Run 1 in Table 2). After
2
for 24 h in THF under nitrogen. These results are
summarized in Table 1. To our delight, the oxidative
further examination of the reaction conditions, we found
that bis(dibenzylideneacetone)palladium (Pd(dba) ) ex-
2
addition of a ArI-containing electron-withdrawing group
hibited an excellent catalytic efficiency for the reaction,
6
EWG such as CO
2
CH
3
, CN, Br, or CF
3
at the ortho-
when allyl chloride was also used as an allylic electro-
phile. Allylbenzene was produced in quantitative yield
by stirring of the reaction solution at 0 °C for 5 min (Run
3). As a reaction medium, TMU was less effective than
diglyme in terms of the reaction time required to reach
position to Zn powder smoothly took place to afford the
corresponding ArZnI 2 in a good yield along with a small
amount of ArH (2-10%) (Runs 1-4). Other ArI, i.e., one
containing EWG at the meta- or para-position or an
electron-donating group EDG, however, were less reac-
tive and the reaction was incomplete under similar
(9) (a) Negishi, E.; Chatterjee, S.; Matsushita, H. Tetrahedron Lett.
1981, 22, 3737. (b) Matsushita, H.; Negishi, E. J . Am. Chem. Soc. 1981,
conditions (Runs 5 and 6).7,8 We then tried to raise the
1
03, 2882.
10) (a) Kalinin, V. N.; Belyakova, I. L.; Derunov, V. V.; Park, J . K.;
reaction temperature over 70 °C, intending to thermally
activate such a reaction system. Simultaneously, the THF
solvent was changed to diglyme (bp 162 °C) or triglyme
(
Schmidhammer, H. Mendeleev Commun. 1995, 22. (b) Kurosawa, H.;
Shiba, K.; Hirako, K.; Kakiuchi, K.; Ikeda, I. J . Chem. Soc., Chem.
Commun. 1994, 1099. (c) Stolle, A.; Ollivier, J .; Piras, P. P.; Salaun,
J .; De Meijere, A. J . Am. Chem. Soc. 1992, 114, 4051. (d) Kurosawa,
H.; Kajimaru, H.; Miyoshi, M.; Ohnishi, H.; Ikeda, I. J . Mol. Catal.
1992, 74, 481. (e) Stolle, A.; Salaun, J .; De Meijere, A. Synlett 1991,
327.
(11) (a) Tsuji, J . In Palladium Reagents and Catalysts; J ohn Wiley
& Sons: Chichester, UK, 1995; p 345. (b) Negishi, E. Palladium and
Nickel Catalysed Reactions of Organozinc Compounds. In Organozinc
Reagents; Knochel, P., Ed.; Oxford University Press: New York, 1999;
p 213.
(
6) Okano, M.; Amano, M.; Takagi, K. Tetrahedron Lett. 1998, 39,
001.
7) As for the difference in reactivity of ArI to Zn powder during
oxidative addition, see ref 2e.
8) Besides these aryl iodides, activated alkenyl iodides are known
3
(
(
2
to react with Zn powder in THF at the bond between the sp -carbon
and iodine to yield the corresponding alkenylzinc compounds: Prasad,
A. S. B.; Knochel, P. Tetrahedron 1997, 53, 16711.
2
196 J . Org. Chem., Vol. 68, No. 6, 2003

Functionalized Arylzinc Compounds in Ethereal Solvent
TABLE 2. P d -Ca ta lyzed Cr oss-Cou p lin g betw een Ar Zn I
TABLE 3. P d -Ca ta lyzed Syn th esis of F u n ction a lized
Allylben zen esa
a
a n d Allyl Electr op h ile
temp, °C/
time
yield,
%
b
Run
R
2
X
3
catalyst
4
1
2
3
4
5
H
2m OAc 3a Pd(PPh3)4
rt/6 h
rt/6 h
4m a
4m a
4m a
4m a
4m a
4m a
4m a
4m a
4m a
78c
80
d
2m
2m Cl
2m
2m
2m
3a Pd(dba)2
3b Pd(dba)2
3b Pd(dba)2
3b Pd(dba)2
3b
0/5 min
0/1 h
0/20 h
0/24 h
0/5 min
99
91
80
0
e
f
g
6
h
7
8
9
0
1
2
2m
3b Pd(OAc)2
92
2m
3b PdCl2(PPh3)2 0/5 min
0
89
i
2m
3b Pd(dba)2
3b Pd(dba)2
3b Pd(dba)2
3b Pd(PPh3)4
0/1 h
0/10 min 4ca
0/10 min 4ca
1
1
1
2-Br 2c
(91)
(89)
2c
2c
j
rt/24 h
4ca
9
a
Molar ratio: 2/3/catalyst ) 1/1.1/0.05. Solvent: diglyme (Runs
b
1
-8 and 11), TMU (Run 9), or THF (Runs 10 and 12). GLC yield.
c
Yields in parentheses are isolated ones. Biphenyl was obtained
d
e
in 7% yield. Biphenyl was obtained in 9% yield. Catalyst: 1 mol
% f Catalyst: 0.1 mol %. Catalyst: 0%. Biphenyl was obtained
g
h
i
j
in 7% yield. Biphenyl was obtained in 8% yield. Conv.: 19%.
SCHEME 1. On e-P ot Syn th esis of Allyla r en e
an end and the selectivity of the desired cross-coupling
product, whereas THF was equally effective as diglyme
(
Runs 9-11).12 In other words, the present study’s ArZnX
2
is far more effective than the one in a polar solvent for
the reaction. As shown in Table 3, a variety of function-
alized ArZnX were successfully utilized in the reaction
in place of PhZnX to afford the corresponding allyl-
benzenes in good yields. Among them, the electron-rich
ones (Runs 7 and 8) tended to react faster than the
2 3
electron-poor ones (Runs 2-6) and the o-CO CH sub-
stituted one (Run 1) needed an exceptionally long reac-
tion time. The reactivity of allylic bromide is higher than
that of allylic chloride (Runs 9 and 10). Substituents in
allylic halides caused a decreasing reactivity (Run 11 in
Table 2 and Run 9 in Table 3), yet their reactions afforded
the desired products in high yields (Runs 9-15), where
the sterically less hindered regioisomers were selectively
or mainly produced (Runs 16-19). Since both reactions
of the oxidative addition of ArI to Zn powder and the
cross-coupling of the resulting ArZnI with allylic halides
a
Molar ratio: 2/3/catalyst ) 1/1.1/0.05. Solvent: THF (Runs
1
-3, 9, 10, 14, and 16) or diglyme (Runs 4-8, 11-13, 15, and 17-
b
1
1
9). Isolated yield. Ratio of isomers was determined by H NMR.
in the presence of Pd(dba)
2
smoothly took place in
c
Z-isomer (16%) and 3h (5%) were contained. d 4GH1:4GH2:4GH3
common ethereal solvents, the one-pot synthesis of allyl-
benzenes starting from ArI was readily achieved (Scheme
) 67:9:24. e 4GH1:4GH2:4GH3 ) 40:20:40.
1
). It should be emphasized that the present aryl-allyl
or Hg13m in terms of (1) the availability of starting
organometallic compounds, including the functional-
cross-coupling possesses advantages over the others using
1
3a
various arylmetallic compounds, for example, involv-
ing Mg,1
3b,c
Cu,
2e,4a,b,e-g,13e
Zn, B,
13d
10d,13f-i
Sn,
10d,13j,k
Tl,
13l
ized ones, especially in the manner of atom econom-
ics,2
e,4a,b,e-g,10d,13d-m,14
(2) the mildness of the utilized
(12) These ethereal solvents are less volatile than THF but did not
reaction conditions and high degree of catalytic ef-
cause trouble with the isolation of the reaction product, since they were
readily transferred from the organic layer to the acidic aqueous one
by the extraction procedure.
2
e,4a,b,e-g,13d-m,15
ficiency,
and/or (3) the simplicity of the
reaction procedure.4
g,13c-e
J . Org. Chem, Vol. 68, No. 6, 2003 2197

Ikegami et al.
In conclusion, application of the simple thermal condi-
tion of 70-130 °C to the reaction system composed of ArI
and Zn powder in ethereal solvent achieved the first
practical synthesis of various ArZnX in the solvent. The
solution served as an outstandingly efficient Ar supply
reagent in the reaction with allylic halides to afford a
variety of functionalized allylbenzenes by the catalysis
mmol) and a 2.0 M THF solution of 2c (0.50 mL, 1.0 mmol) at
0
°C under nitrogen with stirring for 10 min at temperature.
The resulting mixture was quenched by the addition of
aqueous HCl. Workup by extraction with ether, washing with
water, drying with MgSO , and evaporation of the solvent
4
afforded a crude product, which was chromatographed on silica
gel with hexane as the eluent to afford 190 mg of 3-(2-
3
bromophenyl)-2-methyl-1-propene, 4cb (93%): oil; IR (CDCl )
-
of Pd(dba)
2
.
-1 1
1
1
(
1
2
647, 706 cm ; H NMR δ 1.76 (s, 3H), 3.45 (s, 2H), 4.59 (s,
H), 4.86 (s, 1H), 7.03-7.11 (m, 1H), 7.22-7.25 (m, 2H), 7.54
d, J ) 7.4 Hz, 1H); 13C NMR δ 22.5, 43.9, 112.4, 125.1, 127.3,
27.8, 130.9, 132.8, 139.1, 143.5; HRMS calcd for C10
10.0044, found M 210.0025.
Exp er im en ta l Section
H
11Br
+
Gen er a l. All reactions were performed under an atmo-
sphere of nitrogen in oven-dried glassware. Triglyme was
distilled under nitrogen and stored over Molecular Sieves 3A.
Zn powder (from Kanto Chemical), anhydrous THF, and
anhydrous diglyme were purchased and used without further
Meth yl 3-(2-m eth yl-2-p r op en yl)ben zoa te (4eb): oil; IR
-1
1
(
3
CDCl ) 1719, 1650, 708 cm ; H NMR δ 1.67 (s, 3H), 3.36 (s,
2
7
1
H), 3.91 (s, 3H), 4.74 (s, 1H), 4.84 (s, 1H), 7.36-7.39 (m, 2H),
13
.92-7.92 (m, 2H); C NMR δ 22.0, 44.3, 52.0, 112.4,
27.4, 128.3, 130.0, 130.1, 133.5, 140.1, 144.4, 167.2. Anal.
3
purification. The NMR spectra were recorded in CDCl at 200
Calcd for C12
.47.
Eth yl 4-(2-m eth yl-2-p r op en yl)ben zoa te (4fb): oil; IR
14 2
H O : C, 75.76; H, 7.42. Found: C, 75.72; H,
1
13
MHz for H or at 50.3 MHz for C with TMS or chloroform-d
1
7
as the internal standard, respectively.
Gen er a l P r oced u r e for Syn th esis of Ar ylzin c Com -
p ou n d s in Eth er ea l Solven t. Zn powder (654 mg, 10 mmol)
in a reaction flask was heated by a heat-gun for 10 min under
vacuum (1 Torr). To the solid were added aryl iodide (5 mmol),
ethereal solvent (2.5 mL), and trimethylchlorosilane (0.015 mL,
-
1 1
(
3
(
CDCl
3
) 1711, 1652, 706 cm ; H NMR δ 1.39 (t, J ) 7.2 Hz,
H), 1.67 (s, 3H), 3.37 (s, 2H), 4.37 (q, J ) 7.2 Hz, 2H), 4.74
s, 1H), 4.84 (s, 1H), 7.26 (d, J ) 8.2 Hz, 2H), 7.97 (d, J ) 8.2
13
Hz, 2H); C NMR δ 14.3, 22.0, 44.6, 60.8, 112.6, 128.4, 128.9,
0
.15 mmol) at room temperature under nitrogen and stirred
at the stated temperature (70-180 °C) for the stated period
10 min to 24 h). The presence of trimethylchlorosilane is not
129.6, 144.2, 145.1, 166.6. Anal. Calcd for C13
H, 7.90. Found: C, 76.24; H, 7.94.
16 2
H O : C, 76.44;
(
3
3-(2-Br om op h en yl)-1-cycloh exen e (4cc): oil; IR (CDCl )
necessarily indispensable but provides more reproducible
results. The reaction conversion was determined by adding an
internal standard to the resulting mixture and then quenching
the aliquot of supernatant solution with aqueous HCl, followed
by GLC analysis of the remaining aryl iodide. The yield of the
arylzinc compound was similarly determined by quenching the
1650, 708 cm-1
;
1
H NMR δ 1.38-1.71 (m, 3H), 2.01-2.11 (m,
H), 3.85 (ddd, J ) 10.1, 5.4, 2.4 Hz, 1H), 5.65 (dd, J ) 10.0,
.4 Hz, 1H), 5.96 (ddd, J ) 10.0, 6.0, 3.6 Hz, 1H), 7.00-7.11
3
2
(
13
m, 1H), 7.25 (d, J ) 4.2 Hz, 2H), 7.53 (d, J ) 7.8 Hz, 1H);
NMR δ 20.7, 25.0, 30.2, 40.7, 124.4, 127.3, 127.5, 129.2, 129.3,
32.7, 145.0. Anal. Calcd for C12 13Br: C, 60.78; H, 5.53.
Found: C, 60.40; H, 5.57.
-Allyl-2-tr iflu or om eth ylben zen e (4d a ):17 1H NMR δ
.56 (d, J ) 6.4 Hz, 2H), 5.05 (dd, J ) 8.0, 1.6 Hz, 1H), 5.12
s, 1H), 5.95 (ddt, J ) 16.6, 10.4, 6.4 Hz, 1H), 7.25-7.36 (m,
C
1
H
aliquot of solution with I
reproduced aryl iodide.
2
, followed by GLC analysis of the
1
P a lla d iu m -Ca ta lyzed Rea ction of Ar ylzin c Com p ou n d
w ith Allyl Ch lor id e. A typical procedure is as follows: To
3
(
2
2
Pd(dba) (27 mg, 0.05 mmol) were added 3d (0.11 mL, 1.1
H), 7.51 (t, J ) 7.1 Hz, 1H), 7.62 (d, J ) 7.4 Hz, 1H).
E)-1-(4-Meth oxyp h en yl)-2-bu ten e (4GH1):18 1H NMR δ
.67 (d, J ) 6.0 Hz, 3H), 3.24 (d, J ) 5.7 Hz, 2H), 3.77 (s, 3H),
(
(
13) (a) Tamao, K. Coupling Reactions between sp3 and sp2 Carbon
1
Centers. In Comprehensive Organic Synthesis; Trost, B. M., Ed.;
Pergamon Press: Oxford, UK, 1991; Vol. 3, p 435. Mg: (b) Chung, K.-
G.; Miyake, Y.; Uemura, S. J . Chem. Soc., Perkin Trans. 1 2000, 2725.
5.43-5.59 (m, 2H), 6.80-6.85 (m, 2H), 7.05-7.13 (m, 2H).
Z)-1-(4-Meth oxyp h en yl)-2-bu ten e (4GH2):18 1H NMR δ
(
(
c) Boymond, L.; Rottlander, M.; Cahiez, G.; Knochel, P. Angew. Chem.,
1
.71 (d, J ) 5.1 Hz, 3H), 3.34 (d, J ) 5.1 Hz, 2H), 3.78 (s, 3H),
5.44-5.59 (m, 2H), 6.82 (m, 2H), 7.10 (m, 2H).
Meth yl 2-a llylben zoa te (4a a ): see ref 19.
Int. Ed. 1998, 37, 1701. Zn: (d) Kondo, Y.; Fujinami, M.; Uchiyama,
M.; Sakamoto, T. J . Chem. Soc., Perkin Trans. 1 1997, 799. Cu: (e)
Klement, I.; Rottlaender, M.; Tucker, C. E.; Majid, T. N.; Knochel, P.;
Venegas, P.; Cahiez, G. Tetrahedron 1996, 52, 7201 and refs 2e and
2
2
-Allylben zen eca r bon itr ile (4ba ): see ref 20.
-Br om o-1-a llylben zen e (4ca ): see ref 21.
4
2
a,b,e-g. B: (f) Bouyssi, D.; Gerusz, V.; Balme, G. Eur. J . Org. Chem.
002, 2445. (g) Chung, K.-G.; Miyake, Y.; Uemura, S. J . Chem. Soc.,
Perkin Trans. 1 2000, 15. (h) Uozumi, Y.; Danjo, H.; Hayashi, T. J .
Org. Chem. 1999, 64, 3384. (i) Kobayashi, Y.; Ikeda, E. J . Chem. Soc.,
Chem. Commun. 1994, 1789 and ref 10d. Sn: (j) Albeniz, A. C.; Espinet,
P.; Martin-Ruiz, B. Chem. Eur. J . 2001, 7, 2481. (k) Kurosawa, H.;
Kajimaru, H.; Ogoshi, S.; Yoneda, H.; Miki, K.; Kasai, N.; Murai, S.;
Ikeda, I. J . Am. Chem. Soc. 1992, 114, 8417 and ref 10d. Tl: (l) Monti,
D.; Sleiter, G. Gazz. Chim. Ital. 1994, 124, 133. Hg: (m) Zhang, Z.;
Lu, X.; Xu, Z.; Zhang, Q.; Han, X. Organometallics 2001, 20, 3724.
Meth yl 3-a llylben zoa te (4ea ): see ref 22.
Eth yl 4-a llylben zoa te (4fa ): see ref 23.
3
-(4-Meth oxyp h en yl)-2-m eth yl-1-p r op en e (4k b): see ref
24.
(
14) Unlike Zn, the direct reaction between aryl halides and other
(16) Hegedus, L. S. In Transition Metals in the Synthesis of Complex
Organic Molecules, 2nd ed.; University Science Books: Sausalito, CA,
1999; p 256.
metals such as Cu, B, or Sn does not take place under ordinary
conditions.
(
15) The catalytic cycle of the Pd-catalyzed aryl-allyl cross-coupling
(17) Fujimoto, Y.; Suzuki, Y.; Tanaka, Y.; Tominaga, T.; Takeda,
H.; Sekine, H.; Morito, N.; Miyaoka, Y. Heterocycles 1977, 6, 1604.
(18) Lajis, N. H.; Khan, M. N. Tetrahedron 1992, 48, 1109.
(19) Echavarren, A. M.; Stille, J . K. J . Am. Chem. Soc. 1988, 110,
1557.
(20) Nakanishi, K.; Mizuno, K.; Otsuji, Y. Bull. Chem. Soc. J pn.
1993, 66, 2371.
contains three sequential reactions of (1) oxidative addition between
Pd(0) and allylic electrophiles to form the π-allylPd(II) complex, (2)
transmetalation with arylmetallic compound to form the π-allyl(aryl)-
Pd(II) complex, and (3) reductive elimination of the resulting complex
to form the coupling product along with Pd(0). Hegedus described
the reason the conventional reaction utilizing the allylic acetates and
1
6
Pd(PPh
3
)
4
as allylic electrophile and catalyst, respectively, had been
(21) Knight, J .; Parsons, P. J . J . Chem. Soc., Perkin Trans. 1 1989,
979.
(22) Kasibhatla, S.; Bookser, B. C.; Probst, G.; Appleman, J . R.;
Erion, M. D. J . Med. Chem. 2000, 43, 1508.
(23) Meyers, A. I.; Temple, D. L.; Haidukewych, D.; Mihelich, E. D.
J . Org. Chem. 1974, 39, 2787.
slow to develop. It is due to the fact that acetate coordinates quite
strongly to Pd and this, along with the presence of excess phosphine,
slows down the crucial transmetalation step, already the rate-limiting
step.16 In contrast, the utility of not only phosphine-free Pd(0), Pd(dba)
,
2
but also allylic halides in this study might be beneficial to accelerate
the catalytic reaction by promoting the transmetalation due to render-
ing the Pd center more electronically positive.
(24) Coutts, R. T.; Benderly, A.; Mak, A. L. C.; Taylor, W. G. Can.
J . Chem. 1978, 56, 3054.
2
198 J . Org. Chem., Vol. 68, No. 6, 2003

Functionalized Arylzinc Compounds in Ethereal Solvent
3
5.
3
6.
-(4-Met h oxyp h en yl)-1-cycloh exen e (4k c): see ref
-(2-Br om op h en yl)-1-p h en yl-1-p r op en e (4cd ): see ref
-(4-Meth oxyp h en yl)-1-p h en yl-1-p r op en e (4k d ): see ref
3-(4-Meth oxyp h en yl)-1-bu ten e (4GH3): see ref 27.
2
2
2
J O026746S
3
5.
(26) Srogl, J .; Allred, G. D.; Liebeskind, L. S. J . Am. Chem. Soc.
1
997, 119, 12376.
(25) Malkov, A. V.; Davis, S. L.; Baxendale, I. R.; Mitchell, W. L.;
(27) Fassina, V.; Ramminger, C.; Seferin, M.; Monteiro, A. L.
Kocovsky, P. J . Org. Chem. 1999, 64, 2751.
Tetrahedron 2000, 56, 7403.
J . Org. Chem, Vol. 68, No. 6, 2003 2199