Selective halogen - Magnesium exchange reaction via organomagnesium ate complex

Article abstract of DOI:10.1021/jo015597v

Halogen-magnesium exchange of various aryl halides is achieved with a magnesium ate complex at low temperatures. Tributylmagnesate (ⁿBu₃MgLi) induces facile iodine-magnesium exchange at -78 °C. Dibutylisopropylmagnesate (ⁱPrⁿBu₂MgLi) is more reactive than ⁿBu₃MgLi, and this reagent accomplishes selective bromine-magnesium exchange at -78 °C. This procedure is utilized for the preparation of various polyfunctionalized arylmagnesium species. The exchange of alkenyl halides using this method proceeds with retention of configuration of the double bond.

Full text of DOI:10.1021/jo015597v

J . Org. Chem. 2001, 66, 4333-4339
4333
Selective Ha logen -Ma gn esiu m Exch a n ge Rea ction via
Or ga n om a gn esiu m Ate Com p lex
Atsushi Inoue, Kazuya Kitagawa, Hiroshi Shinokubo, and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,Yoshida,
Sakyo-ku, Kyoto 606-8501, J apan
oshima@fm1.kuic.kyoto-u.ac.jp
Received February 27, 2001
Halogen-magnesium exchange of various aryl halides is achieved with a magnesium ate complex
at low temperatures. Tributylmagnesate (nBu3MgLi) induces facile iodine-magnesium exchange
at -78 °C. Dibutylisopropylmagnesate (iPrnBu2MgLi) is more reactive than nBu3MgLi, and this
reagent accomplishes selective bromine-magnesium exchange at -78 °C. This procedure is utilized
for the preparation of various polyfunctionalized arylmagnesium species. The exchange of alkenyl
halides using this method proceeds with retention of configuration of the double bond.
In tr od u ction
electron-defficient aryl halides or alkenyl halides having
an oxygen functionality acting as a metal directing group.
The utility of organometallic ate complexes such as R2-
CuLi, R3ZnLi, R4AlLi, and R3MnLi in organic synthesis
is well-recognized,6 and these complexes are known to
induce halogen-metal exchange reactions in some cases.7
Since a magnesium ate complex (R3MgLi) was first
reported in 1951, several investigations on its structure
have been reported.8 However, synthetic application of
magnesate reagents still remains unexplored.9 Herein we
wish to report a versatile method for the preparation of
various organomagnesium reagents which makes use of
the magnesium ate complex.10
Organomagnesium reagents are synthetic tools of great
importance, and numerous reports for the preparation
of various organomagnesium compounds have been pub-
lished.1 Methods for the preparation of organomagnesium
compounds are usually based on (1) direct metalation of
organic halides with metallic magnesium, (2) deproto-
nation, (3) transmetalation from other organometallics,
or (4) halogen-magnesium exchange. For the preparation
of polyfunctional organomagnesium compounds, method
3 or 4 is particularly attractive. Very recently, Knochel
et al. have shown that polyfunctional aryl- and alkenyl-
magnesium reagents can be prepared by the halogen-
magnesium exchange reaction with iPrMgBr at low
temperatures.2-5 However, the substrates are limited to
Resu lts a n d Discu ssion
(1) Iod in e-Ma gn esiu m Exch a n ge of Ar yl Iod id es.
Lithium tributylmagnesate (nBu3MgLi) was easily pre-
pared by mixing butylmagnesium bromide and butyl-
lithium in a 1:2 ratio in THF at 0 °C. Treatment of
* To whom correspondence should be addressed. Phone: +81-75-
753-5523. Fax: +81-75-753-4863.
(1) (a) Wakefield, B. J . Organomagnesium Methods in Organic
Synthesis; Academic Press: London, 1995. (b) Handbook of Grignard-
Reagents; Silverman, G. S., Rakita, P. E. Eds.; Marcel Dekker: New
York, 1996. (c) Grignard Reagents: New Developments; Richey, H. G.,
J r., Eds.; Wiley & Sons: New York, 1999.
(2) For review, see: (a) Rottla¨nder, M.; Boymond, L.; Be´rillon, L.;
Lepreˆtre, A.; Varchi, G.; Avolio, S.; Laaziri, H.; Que´guiner, G.; Ricci,
A.; Cahiez, G.; Knochel, P. Chem. Eur. J . 2000, 6, 767. (b) Boudier, A.;
Bromm, L. O.; Lotz, M.; Knochel, P. Angew. Chem. 2000, 112, 4584;
Angew. Chem., Int. Ed. 2000, 39, 4414.
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Chem. 1998, 110, 1801; Angew. Chem., Int. Ed. Engl. 1998, 37, 1701.
(b) Varchi, G.; Ricci, A.; Cahiez, G.; Knochel, P. Tetrahedron 2000, 56,
2727. (c) Abarbri, M.; Dehmel, F.; Knochel, P. Tetrahedron Lett. 1999,
40, 7449. (d) Be´rillon, L.; Lepreˆtre, A.; Turck, A.; Ple´, N.; Que´guiner,
G.; Cahiez, G.; Knochel, P. Synlett 1998, 1359. (e) Abarbri, M.; Knochel,
P. Synlett 1999, 1577. (f) Dehmel, F.; Abarbri, M.; Knochel, P. Synlett
2000, 345. (g) Abarbri, M.; Thibonnet, J .; Be´rillon, L.; Dehmel, F.;
Rottla¨nder, M.; Knochel, P. J . Org. Chem. 2000, 65, 4618. (h)
Rottla¨nder, M.; Boymond, L.; Cahiez, G.; Knochel, P. J . Org. Chem.
1999, 64, 4, 1080. (i) Thibonnet, J .; Knochel, P. Tetrahedron Lett. 2000,
41, 3319. (j) Avolio, S.; Malan, C.; Marek, I.; Knochel, P. Synlett 1999,
1820.
(4) (a) Nishiyama, H.; Isaka, K.; Itoh, K.; Ohno, K.; Nagase, H.;
Matsumoto, K.; Yoshiwara, H. J . Org. Chem. 1992, 57, 407. (b) Smith,
C. F.; Moore, G. J .; Tamborski, C. J . Organomet. Chem. 1971, 33, C21.
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Martin, G. J .; Mechin, B.; Leroux, Y.; Paulmier, Cl.; Meunier, J . C.; J .
Organomet. Chem. 1974, 67, 327. (e) Furukawa, N.; Shibutani, T.;
Fujihara, H. Tetrahedron Lett. 1987, 28, 5845. (f) Tre´court, F.; Breton,
G.; Bonnet, V.; Mongin, F.; Marsais, F.; Que´guiner, G. Tetrahedron
Lett. 1999, 40, 4339.
(6) Oshima, K. J . Organomet. Chem. 1999, 575, 1.
(7) Halogen-metal exchange with trialkylzincate or dialkylcuprate
have been reported. (a) Kondo, Y.; Takazawa, N.; Yamazaki, C.;
Sakamoto, T. J . Org. Chem. 1994, 59, 4717. (b) Uchiyama, M.; Koike,
M.; Kameda, M.; Kondo, Y.; Sakamoto, T. J . Am. Chem. Soc. 1996,
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N.; Koike, M.; Kondo, Y.; Sakamoto, T. J . Am. Chem. Soc. 1998, 120,
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T. Angew. Chem. 1996, 108, 818; Angew. Chem., Int. Ed. Engl. 1996,
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K.; Kaji, R.; Oku, A. J . Org. Chem. 1993, 58, 4897.
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Coates, G. E.; Heslop, J . A. J . Chem. Soc. (A) 1968, 514. (d) Greiser,
T.; Kopf, J .; Thoennes, D.; Weiss, E. Chem. Ber. 1981, 114, 209.
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39, 3258. (b) Richey, H. G., J r.; Farkas, J ., J r. Tetrahedron Lett. 1985,
26, 275. (c) Richey, H. G., J r.; Farkas, J ., J r. Organometallics 1990, 9,
1778. (d) Yasuda, M.; Ide, M.; Matsumoto, Y.; Nakata, M. Synlett 1998,
899. (e) Yasuda, M.; Ide, M.; Matsumoto, Y.; Nakata, M. Bull. Chem.
Soc. J pn. 1998, 71, 1417. (f) Ide, M.; Yasuda, M.; Nakata, M. Synlett
1998, 936. (g) Ide, M.; Yasuda, M.; Nakata, M. Bull. Chem. Soc. J pn.
1999, 72, 2491. (h) Kamienski, C. W.; Gastonia, N. C.; Eastham, J . F.
U.S. Patent 3,847,883, 1974; Chem. Abstr. 1975, 82, 58590b. (i)
Castaldi, G.; Borsotti, G. Eur. Pat. Appl. EP 491,326, 1992; Chem.
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Tomimoto, K.; Mase, T. Tetrahedron Lett., in press.
(10) A part of this paper was published in
a communication.
(5) Lee, J .; Velarde-Ortiz, R.; Guijarro, A.; Wurst, J . R.; Rieke, R.
D. J . Org. Chem. 2000, 65, 5428.
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10.1021/jo015597v CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/12/2001

4334 J . Org. Chem., Vol. 66, No. 12, 2001
Inoue et al.
Sch em e 1
Ta ble 1. Iod in e-Ma gn esiu m Exch a n ge of Ar yl Iod id es
Sch em e 2
Sch em e 3
nBu3MgLi at -78 °C furnished the desired magnesium
compound which reacted with allyl bromide in the
presence of CuCN‚2LiCl12 (Scheme 1). The reaction of
o-iodobenzoates (1p and 1q) with heptanal after the
exchange provided 3-hexylphthalide (4) as a major prod-
uct. Interestingly, this exchange reaction was much faster
than the nucleophilic attack of the butyl group to an
aldehyde. The addition of nBu3MgLi to a mixture of
o-iodobenzoate ester (1p or 1q) and heptanal provided
3-hexylphthalide (4) as the single product (Scheme 2).
The ester group of ethyl (2-iodophenoxy)acetate (1s) could
survive under the reaction conditions, and 3-coumara-
none (5) was obtained in 85% yield via the intramolecular
attack of the resultant magnesium reagent (Scheme 3).
(2) Br om in e-Ma gn esiu m Exch a n ge of Ar yl Br o-
m id es. We next turned our attention on the bromine-
magnesium exchange reaction of aryl bromides, because
it is desirable to use readily available aryl bromides as
substrates. Various aryl bromides 6 could be efficiently
converted into the corresponding arylmagnesium com-
pounds with nBu3MgLi at 0 °C. The resultant arylmag-
nesium species could be trapped by various electrophiles
such as aldehydes or allyl bromide (Table 2). Several
comments are worth noting. (1) Both electron-rich and
electron-deficient aryl bromides give satisfactory results
in this magnesate-induced reaction. In contrast, isopro-
pylmagnesium bromide-induced exchange reaction often
requires electron-withdrawing groups on the aromatic
ring.2,3c,4a,b (2) In contrast to aryl iodides, the exchange
reaction of aryl bromides does not go to completion at
-78 °C in some cases. (3) A half-equivalent of the reagent
a
nBu3MgLi (0.5 equiv) was used.
various aryl iodides 1 with 1.2 equiv of nBu3MgLi followed
by an addition of electrophiles afforded the desired
products 3 in good to excellent yields (Table 1).11
Electron-rich aryl iodides such as o-, m-, or p-iodoani-
sole can be converted into the corresponding arylmag-
nesates at -78 °C (entries 3-5). The amount of the
magnesate reagent can be reduced to 0.5 equiv to the
substrate (entry 2). This result indicates that two of the
three butyl groups in the reagent can work for the
exchange reaction.
The fact that the iodine-magnesium exchange reaction
proceeds at -78 °C encouraged us to investigate the
reaction of functionalized aryl iodides. Indeed, the treat-
ment of tert-butyl p-iodobenzoate (1r ) with 0.5 equiv of
(11) In the trapping reaction of resultant magnesate (ArnBu2MgLi)
with electrophiles, no significant difference in the migratory attitude
of the ligands (Ar vs nBu) was observed. For example, the reaction of
ArnBu2MgLi (Ar ) 4-methoxyphenyl) with 1.0 equiv of PhCHO
provided a mixture of ArCH(OH)Ph and nBuCH(OH)Ph in a 1:2 ratio.
Therefore, we recommend the use of more than 3 equiv of electrophiles.
(12) (a) Knochel, P.; Yeh, M. C. P.; Berk, S. C.; Talbert, J . J . Org.
Chem. 1988, 53, 2390. (b) Knochel, P.; Singer, R. D. Chem. Rev. 1993,
93, 2117. (c) Knochel, P. Synlett 1995, 393.

Halogen-Magnesium Exchange Reaction
J . Org. Chem., Vol. 66, No. 12, 2001 4335
Ta ble 2. Br om in e-Ma gn esiu m Exch a n ge of Ar yl
is sufficient. (4) Sterically hindered halides such as 6m
and 6n can be also metalated efficiently. In these cases,
a catalytic amount of CuCN‚2LiCl improves efficiency of
the trapping reaction with allyl bromide.12
Br om id es
This magnesate-induced exchange reaction was com-
pared with the conventional bromine-lithium exchange
(Scheme 4). Treatment of allyl 2-bromophenyl ether (6o)
with nBuLi in THF at 0 °C afforded a complex mixture
containing dihydrobenzofuran derivative 7 which re-
sulted from bromine-lithium exchange and subsequent
intramolecular carbolithiation.13 In contrast, the mag-
nesate reagent induced the clean bromine-magnesium
exchange providing the magnesium species 2o.14
With this successful exchange procedure in hand, we
examined the preparation of functionalized arylmagne-
sium compounds from the corresponding aryl bromide.
n
The reaction of aryl bromides with Bu3MgLi did not go
to completion under the same conditions as the reaction
of aryl iodides. To enhance the reactivity of a magnesate
reagent, an isopropyl group was introduced on magne-
i
sium as a ligand. The reagent PrnBu2MgLi was prepared
i
by mixing PrMgBr and nBuLi in a 1:2 ratio. With this
reagent the exchange reaction proceeded smoothly at -78
°C, and the subsequent addition of various electrophiles
provided the desired coupling products in moderate to
good yields (Table 3). Functional groups such as ester,
amide and cyano groups are tolerable during the ex-
change procedure. The addition of a catalytic amount of
CuCN‚2LiCl was necessary when allyl bromide was
employed as an electrophile.12 The cyano group was
tolerable at even -40 °C and, therefore, the exchange
reaction of bromobenzonitriles with nBu3MgLi was per-
formed at -40 °C (Scheme 5). Aryl bromide 6y containing
a bromo acetal moiety at the proper position provided
2-alkoxy-substituted coumaran 8 in moderate yield via
intramolecular nucleophilic substitution without decom-
position of the acetal moiety (Scheme 6).
(3) Ha logen -Ma gn esiu m Exch a n ge of Dih a loa r e-
n es. The preparation of polymetalated aromatic com-
pounds has been a topic of organometallic chemistry.15
In addition, selective metalation of polyhaloarenes pro-
vides an efficient methodology to synthesize substituted
aromatic compounds. We then investigated the selective
exchange reaction of dihalogenated aromatics (Table 4).
In the case of p-bromoiodobenzene (9a ), none of the
bromide-magnesium exchange proceeded (entry 1). Only
one of two bromines of m- or p-dibromobenzene was
exchanged (entries 2 and 3). On the other hand, p-
diiodobenzene (9d ) was converted into dimagnesiated
benzene upon treatment with 1.0 equiv of nBu3MgLi
(entry 4), while dimetalation of m-diiodobenzene (9e)
required 2.0 equiv of the reagent to furnish m-dimagne-
siobenzene (entry 6). The reagent nBuMe2MgLi was
employed to induce selective monomagnesiation of p-
diiodobenzene (entry 5). Because the methyl ligand on
magnesium is less reactive than the butyl group, the
second exchange is enough slow to be controlled. In
contrast to p-dibromobenzene (entry 3), dimagnesiated
biphenyl was formed quantitatively via the double ex-
change reaction of 4,4′-dibromobiphenyl (10) (entry 7).
(13) Bailey, W. F.; Carson, M. W. J . Org. Chem. 1998, 63, 9960, and
references therein.
(14) Carbomagnesiation has been reported to be slow. Richey, H.
G., J r.; Veale, H. S. Tetrahedron Lett. 1975, 615, and references therein.
(15) (a) Rot, N.; Bickelhaupt, F. Organometallics 1997, 16, 5027.
(b) Bickelhaupt, F. Chem. Soc. Rev. 1999, 28, 17.
a
b
nBu3MgLi (0.5 eq.) was used. nBuMe2MgLi was used.
c CuCN‚2LiCl (30 mol %) was added.

4336 J . Org. Chem., Vol. 66, No. 12, 2001
Inoue et al.
Sch em e 4
Ta ble 3. Br om in e-Ma gn esiu m Exch a n ge of Ar yl
Sch em e 5
Br om id es Bea r in g Rea ctive F u n ction a lities
Sch em e 6
Ta ble 4. Ha logen -Ma gn esiu m Exch a n ge of
Dih a loa r en es
a
b
nBu3MgLi was used. CuCN‚2LiCl (30 mol %) was added.
Treatment of o-dibromobenzene (9f) with nBu3MgLi
yielded 2-butylphenylmagnesium 15. The formation of 15
arises from the addition of the butyl group to benzyne
which is derived from 2-bromophenylmagnesium 14 via
1,2-elimination.16 (Scheme 7).
mopyridine with nBu3MgLi at 0 °C followed by an
addition of propanal furnished the desired product in low
yield along with various byproducts. To prevent side
reactions induced by an excess butyl group, the ate
n
complex BuMe2MgLi was employed. This reagent gave
(4) Ha logen -Ma gn esiu m Exch a n ge of Heter oa r yl
Ha lid es. The bromine-magnesium exchange of 3-bro-
satisfactory results for the preparation of pyridylmag-
nesiums (Table 5).3d,g,4c-f 2-Iodo-, 2-bromo-, and 3-bro-
mopyridine were converted into the corresponding py-
ridylmagnesiums(entries1-4).Thereaction of2-chloropyridine
(16) Ghosh, T.; Hart, H. J . Org. Chem. 1988, 53, 3555, and
references therein.

Halogen-Magnesium Exchange Reaction
J . Org. Chem., Vol. 66, No. 12, 2001 4337
Ta ble 6. Iod in e-Ma gn esiu m Exch a n ge of Alk en yl
Sch em e 7
Iod id es
Ta ble 5. Ha logen -Ma gn esiu m Exch a n ge of Heter oa r yl
Ha lid es
a
b
nBu3MgLi was used. Trapping reaction was performed at
-78 °C.
provided a complex mixture.17 Thienylmagnesium can be
prepared in good yield via the exchange reaction with
nBu3MgLi at 0 °C (entry 5).
(5) H a logen -Ma gn esiu m E xch a n ge of Alk en yl
Ha lid es. This new procedure is also applicable for the
preparation of alkenylmagnesates from alkenyl iodides
(Table 6). The iodine-magnesium exchange of alkenyl
iodides 23 proceeds with complete retention of configu-
ration of the double bond. The reaction of nonactivated
a
b
The exchange reaction was performed at -78 °C. nBu3MgLi
was used. c CuCN‚2LiCl (30 mol %) was added.
i
iodoalkene with PrMgBr is reported to require increased
reaction time at room temperature.3h In contrast, this
method can achieve the complete exchange within 1 h
at -78 °C. The presence of an ester functionality is
compatible with the formation of alkenylmagnesate at
-78 °C (Scheme 8).
Sch em e 8
Unfortunately, the bromine-magnesium exchange of
alkenyl bromides3i was disappointing. Because the ex-
change was slow, the dehydrobromination and deproto-
nation afforded magnesium acetylides. The results are
shown in Table 7. Especially in the case of the Z isomer
25b, the acetylenic products 26A and 26B were obtained
predominantly.
iodides 27, considerable isomerization18 was observed in
the preparation of trimethylsilyl-substituted alkenyl-
magnesium (entries 1 and 2). For tert-butyldimethylsilyl-
The results of the exchange reaction of 1-silyl-1-
haloalkenes are shown in Table 8. In the case of alkenyl
(18) Silyl-substituted alkenyl halides have been reported to isomer-
ize easily in the presence of organometallic reagents. (a) Zweifel, G.;
Murray, R. E.; On, H. P. J . Org. Chem. 1981, 46, 1292. (b) Negishi, E.;
Takahashi, T. J . Am. Chem. Soc. 1986, 108, 3402.
(17) The deprotonation at 5-position of 2-chlorothiophene occurred
under the same conditions.

4338 J . Org. Chem., Vol. 66, No. 12, 2001
Inoue et al.
Ta ble 7. Br om in e-Ma gn esiu m Exch a n ge of Alk en yl
Sch em e 9
Br om id es
Sch em e 10
undergo metalation reactions.19 We investigated the
halogen-magnesium exchange reaction of cyclopropyl
halides. Treatment of cyclopropyl bromide (30) with 1.0
equiv of nBu3MgLi for 0.5 h at 0 °C followed by an
addition of benzaldehyde furnished R-cyclopropylbenzyl
alcohol (31) in 91% yield. Two-fold amount of 1-phenyl-
pentanol (32), which was separable from the desired
product by silica gel column chromatography, was also
obtained. An attempt to reduce the amount of the
magnesate reagent decreased the yield of 31 (Scheme 10).
Ta ble 8. Ha logen -Ma gn esiu m Exch a n ge of
1-Silyla lk en yl Ha lid es
Con clu sion s
We have demonstrated that a magnesium ate complex,
R3MgLi, induces the facile halogen-magnesium ex-
change of various aryl halides and alkenyl halides. The
reaction proceeded smoothly at low temperatures. The
reactivity of magnesate reagents is tunable by a proper
choice of ligands on magnesium. Because of these notable
characteristics of the reaction, one can prepare function-
alized organomagnesium reagents using the magnesate-
induced halogen-magnesium exchange reaction.
Exp er im en ta l Section
1H NMR (300 MHz) and 13C NMR (75.3 MHz) spectra were
taken on a Varian GEMINI 300 spectrometer in CDCl3 as a
solvent, and chemical shifts were given in δ value with
tetramethylsilane as an internal standard. IR spectra were
determined on a J ASCO IR-810 spectrometer. Mass spectra
were determined on a J EOL J MS-700 spectrometer. TLC
analyses were performed on commercial glass plates bearing
0.25 mm layer of Merk Silica gel 60F254. Column chromatog-
raphy was done with silica gel (Wakogel 200 mesh). The
analyses were carried out at the Elemental Analysis Center
of Kyoto University. Tetrahydrofuran (THF) was freshly
distilled from sodium benzophenone ketyl before use. Grignard
reagents were prepared from the corresponding alkyl halide
and Mg turning (Nacalai tesque, INC), and the concentration
was titrated with 2-butanol using 1,10-phenanthroline as the
indicator. Unless otherwise noted, materials obtained from
commercial suppliers were used without further purification.
Aldehydes were distilled and stocked under argon.
P r oced u r e for th e Br om in e-Ma gn esiu m Exch a n ge of
Ar yl Br om id es. To a solution of butylmagnesium bromide (1.2
mL, 1.0 M solution in THF, 1.2 mmol) in THF (2 mL) was
added butyllithium (1.5 mL, 1.6 M solution in hexane, 2.4
mmol) at 0 °C, and the mixture was stirred for 10 min. A
solution of 4-bromoanisole (6g, 187 mg, 1.0 mmol) in THF (2
mL) was introduced dropwise. After stirring for 0.5 h at 0 °C,
the mixture was cooled to -78 °C and benzaldehyde (0.37 mL,
3.6 mmol) was added. After stirring for 0.5 h at -78 °C, the
reaction was quenched with saturated aqueous NH4Cl. The
a
b
R ) nC6H13
.
CuCN‚2LiCl (30 mol %) was added.
substituted alkenylmagnesium, almost perfect isomer-
ization was observed (entries 3 and 4). Obviously, these
results reflect strong preference of the bulky silyl group
in the trans orientation to the alkyl group. On the other
hand, the bromine-magnesium exchange is slower than
the isomerization of bromosilylalkenes. Therefore, (E)-
silylalkenylmagnesiums were obtained regardless of the
bulkiness of the silyl groups (entries 5-10). The resulting
1-silylalkenylmagnesiums could be trapped with chlo-
rotrimethylsilane in the presence of a catalytic amount
of CuCN‚2LiCl12 to afford 1,1-disilylalkene (Scheme 9).
(6) Br om in e-Ma gn esiu m Exch a n ge of Cyclop r o-
p yl Br om id e. Because a bond of strained cyclopropyl
rings has significant s-character, cyclopropyl halides can
(19) (a) Lukina, M. Yu. Russ. Chem. Rev. (Engl. Transl.) 1962, 31,
419. (b) Eaton, P. E.; Lee, C.-H.; Xiong, Y. J . Am. Chem. Soc. 1989,
111, 8016. (c) Walborski, H. M.; Impastato, F. J .; Young, A. E. J . Am.
Chem. Soc. 1964, 86, 3283.

Halogen-Magnesium Exchange Reaction
J . Org. Chem., Vol. 66, No. 12, 2001 4339
mixture was extracted with ethyl acetate, and the combined
organic layers were dried over anhydrous Na2SO4. Concentra-
tion and purification by chromatography provided 1-(4-meth-
oxyphenyl)-1-phenylmethanol (3gE, 193 mg, 0.90 mmol) in
90% yield.
(s, 9H), 3.73 (d, J ) 6.3 Hz, 2H), 5.01 (d, J ) 16.8 Hz, 1H),
5.03 (d, J ) 10.5 Hz, 1H), 6.02 (ddt, J ) 10.5, 16.8, 6.3 Hz,
1H), 7.22-7.29 (m, 2H), 7.36-7.43 (m, 1H), 7.78 (dd, J ) 1.5,
8.4 Hz, 1H); 13C NMR (CDCl3) δ 28.07, 38.22, 81.16, 115.53,
126.10, 130.32, 130.78, 131.41, 132.00, 137.59, 140.66, 167.33.
Found: C, 76.98; H, 8.49%. Calcd for C14H18O2: C, 77.03; H,
8.31%.
P r ep a r a tion of P olyfu n ction a l Ar ylm a gn esiu m s fr om
Ar yl Br om id es. To a solution of isopropylmagnesium bromide
(1.2 mL, 1.0 M solution in THF, 1.2 mmol) in THF (2 mL) was
added butyllithium (1.5 mL, 1.6 M solution in hexane, 2.4
mmol) at 0 °C, and the mixture was stirred for 10 min. The
resulting yellow solution was cooled to -78 °C, and a solution
of tert-butyl 2-bromobenzoate (6q, 304 mg, 1.0 mmol) in THF
(2 mL) was introduced dropwise. After the mixture was stirred
for 1 h, CuCN‚2LiCl (0.3 mL, 1.0 M solution in THF, 0.3 mmol)
and allyl bromide (0.35 mL, 4.0 mmol) were sequentially
added. After stirring for 0.5 h at -78 °C, the reaction was
quenched with saturated aqueous NH4Cl. The mixture was
extracted with hexane, and the combined organic layers were
dried over anhydrous Na2SO4. Concentration and purification
by chromatography provided tert-butyl 2-allylbenzoate (3qB,
215 mg, 0.99 mmol) in 99% yield: Rf ) 0.74 (hexane/ethyl
Ack n ow led gm en t. This work was supported by
Grant-in-Aid for Scientific Research (No. 10208208)
from the Ministry of Education, Culture, Sports, Science
and Technology. A.I. is grateful to Research Fellowships
of the J apan Society for the Promotion of Science for
Young Scientists. We thank Dr. Toshiaki Mase (Banyu
Pharmaceutical Co., Ltd.) for helpful discussions.
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
1
acetate ) 5/1); IR (neat) 1711 cm-1; H NMR (CDCl3) δ 1.59
J O015597V