Deprotonation of fluoro aromatics using lithium magnesates

Article abstract of DOI:10.1016/j.tetlet.2004.07.077

Activated fluoro aromatics are deprotonated using lithium magnesates. 3-Fluoropyridine was deprotonated on treatment with 1/3 equiv of Bu ₃MgLi in THF at -10°C. The lithium arylmagnesate formed was either trapped with electrophiles or involved

Full text of DOI:10.1016/j.tetlet.2004.07.077

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6697–6701
Deprotonation of fluoro aromatics using lithium magnesates
a
a
Ha c¸ an Awad, Florence Mongin, Fran c¸ ois Tr e´ court, Guy Qu e´ guiner,
a,*
a
a
b
b
Francis Marsais, Fernando Blanco, Bel e´ n Abarca and Rafael Ballesteros
b
a
Laboratoire de Chimie Organique Fine et H e´ t e´ rocyclique, UMR 6014, IRCOF, CNRS Universit e´ et INSA de Rouen,
Place E. Blondel, BP 08, 76131 Mont-Saint-Aignan C e´ dex, France
b
Departamento de Qu ı´ mica Org a´ nica, Facultad de Farmacia, Universidad de Valencia, Avda. Vicente Andr e´ s Estell e´ s s/n,
6100 Burjassot (Valencia), Spain
4
Received 20 April 2004; revised 6 July 2004; accepted 19 July 2004
Abstract—3-Fluoropyridine was deprotonated on treatment with 1/3equiv of Bu MgLi in THF at ꢀ10°C. The lithium arylmagne-
3
sate formed was either trapped with electrophiles or involved in a palladium-catalyzed cross-coupling reaction with 2-bromopyr-
idine. The use of a less nucleophilic lithium-magnesium-dialkylamide, (TMP) MgLi, allowed the reaction of 3-fluoroquinoline,
3
0
giving the 2,2 -dimeric derivative. 2-Fluoropyridine and 2,6-difluoropyridine were deprotonated using 1/3equiv of the highly coor-
dinated magnesate Bu MgLi in THF at ꢀ10°C in the presence of a substoichiometric amount of 2,2,6,6-tetramethylpiperidine. 1,3-
4
2
Difluorobenzene reacted similarly when treated with Bu
TMEDA.
3
MgLi; the reactivity of the base proved to be enhanced by the presence of
Ó 2004 Elsevier Ltd. All rights reserved.
We describe the first deprotonation–electrophilic trap-
ping sequences using magnesates.
magnesiums rarely deprotonate such substrates
5
because 1,4-addition reactions occur more easily.
The preparation of functional heterocycles is an impor-
tant synthetic goal because of the multiple applications
of these molecules. Among the methods developed, lith-
More recently, deprotonations of pyridine, quinoline
and isoquinoline rings have been accomplished at room
temperature through the formation of an arylzincate
using lithium di-tert-butyl(2,2,6,6-tetramethylpiperid-
ino)zincate or lithium di-tert-butyl(diisopropylam-
1
iation is convenient to allow a number of polyfunctional
azine (pyridines, quinolines,. . .) and diazine syntheses
since lithiated derivatives display a high reactivity to-
6
ino)zincate as a base.
2
wards many electrophilic functions. Nevertheless, this
methodology often requires low temperatures, which
can be difficult to realize on an industrial scale. In addi-
tion, unlike organoboron, organotin, organozinc and
organomagnesium compounds, organolithiums can
The arylmagnesates reacting with a wider range of
electrophiles than arylzincates, we have been interested
in deprotonation reactions of aromatics using lithium
magnesates.
3
hardly be involved in cross-coupling reactions.
Since a magnesium ate complex (R MgLi) was first pub-
3
7
Some substituted azines can be deprotonated at higher
temperatures using the Hauser base TMPMgCl (TMP =
lished in 1951, several investigations on its structure
8
have been reported. However, the synthetic applica-
tions of magnesate reagents remained unexplored until
very recently. While halogen–magnesium exchanges
using organomagnesium ate complexes were described
in the benzene, thiophene, pyridine and quinoline ser-
4
2
,2,6,6-tetramethylpiperidino); because of its weak
9
reactivity when compared to alkylmagnesium halides,
a large excess (6–8equiv) has in general to be used to en-
sure good yields. Alkylmagnesium halides and dialkyl-
9
i,l,m,p–r
ies,
few studies have been devoted to aromatic
deprotonation. Mulvey documented in 1999 the prepa-
ration of a mixed-metal sodium–magnesium macrocy-
clic amide, which behaves like a template for the site
Keywords: Deprotonation; Ate complexes; Magnesium; Fluorine.
*
Corresponding author. Tel.: +33 (0)235522900; fax: +33
0)235522962; e-mail: florence.mongin@insa-rouen.fr
1
0
(
selective dideprotonation of benzene and toluene. This
0
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.07.077

6698
H. Awad et al. / Tetrahedron Letters 45 (2004) 6697–6701
process cannot be used as it is for synthetic purposes be-
cause it involves a large excess of arene (5mmol out of
the 5mL used are consumed in the reaction). Very re-
cently, Richey observed that treating benzene halides
with magnesates partially results in benzyne forma-
tion. Even if the organometallic precursors have not
been intercepted by electrophiles, the results show
magnesates are capable of abstracting aromatic protons.
which could consume the quinoline organometallics pre-
sent in the reaction mixture by nucleophilic substitution.
The access to arylpyridines was here investigated via
hydrogen–magnesium exchange, avoiding such compli-
cations. To this purpose, the intermediate (3-fluoro-
4-pyridyl)magnesate was subjected to reaction with
2-bromopyridine. As for the quinoline series cou-
9
s
9
q,r
plings,
catalysis using 1,1 -bis(diphenylphosphino)ferrocene
the reaction was successful under palladium
0
1
4
Herein, we describe the synthesis and reactivity of lith-
ium arylmagnesates through the regioselective deproto-
nation of activated aromatic fluorides using lithium
magnesates.
(dppf) as ligand, and afforded the bipyridine 1e in a
yield comparable to those obtained when quenching
with electrophiles (Scheme 1).
1
5
The procedure was applied to 3-fluoroquinoline but
only gave a complex mixture containing butylated prod-
ucts. Due to its lower LUMO level, quinoline is more
prone to nucleophilic attack, and addition of either the
base or the formed lithium arylmagnesate to the sub-
strate is favoured over deprotonation. Predominant
addition reactions have been previously observed during
lithiation experiments using BuLi-TMEDA in diethyl
ether while LDA in THF ensures a clean deprotona-
The first experiments were conducted on 3-fluoro-
pyridine using 1/3equiv of lithium tributylmagnesate
(
Bu MgLi) in THF at ꢀ10°C. Trapping the intermedi-
3
ate lithium magnesate with iodine, 4-anisaldehyde,
,4,5-trimethoxybenzaldehyde and allyl bromide af-
3
forded the iodide 1a, the alcohols 1b,c and the allyl-
1
1
12
1
3
ated compound 1d in moderate yields. The proton
abstraction occurs at C4, as previously noticed using
BuLi-TMEDA, LIC-KOR (mixture of BuLi and potas-
sium tert-butoxide) or LDA in THF (thermodynamic
2
tion. We therefore turned to the less nucleophilic li-
thium-magnesium-dialkylamide (TMP) MgLi, which has
3
2
a,b
control).
through 3,4-pyridyne formation is not observed at
10°C (the yield is limited only by the deprotonation
step), while 3-fluoro-4-lithiopyridine decomposes
The degradation of the arylmagnesate
never been employed for the purpose of deprotonating
arenes. Such bases (diisopropylamino instead of TMP)
ꢀ
ꢀ
have been regarded as sources of hyperbasic ÔR N Õ ani-
2
+
ons, which separate from the cations ÔLiMg[NR ] Õ in
2
2
2
a,b
16
between ꢀ60 and ꢀ20°C. In addition, the yields
using BuLi-TMEDA (60%), Bu MgLi (55%) and
hydrocarbon solutions. Insofar as THF is our solvent,
one can wonder if 1equiv or 1/3equiv should be em-
ployed in the deprotonation process. Consequently,
both experiments were performed in THF at ꢀ10°C.
After addition of iodine, iodinated 3-fluoropyridines
were obtained in very low yields, the main product being
3
Bu MgLi(TMEDA) (74%) were compared (3,4,5-tri-
3
methoxybenzaldehyde was used as the electrophile):
the latter proved to be more efficient.
0
17
Since treatment of 3-fluoropyridine with BuLi-TMEDA
or BuLi-DABCO complexes in diethyl ether leads to C2
the 2,2 -dimer 2. Since a better yield was obtained
using 1/3equiv of base, its formation could be explained
by a deprotonation at C2, followed by the migration
2
metallation (kinetic control), the reaction using
Bu MgLi was also carried out in the less basic solvent
9
k
of the 3-fluoro-2-quinolyl group,
Scheme 2.
as depicted in
3
diethyl ether at ꢀ10°C. Under these conditions, a mix-
ture was produced and the iodide 1a was isolated in a
low yield (<30%).
The regioselectivity of the deprotonation is surpris-
ing, since lithiation using lithium dialkylamides
2
a,b
We previously reported the first cross-couplings with
lithium arylmagnesates: the lithium tri(quinolyl)magne-
sates could react with aromatic halides under transition
metal-catalysis to give the corresponding arylquino-
occurs at C4;
size of (TMP) MgLi, when compared with the lithium
it could be attributed to the important
3
bases. Indeed, the hydrogen at C5 could hinder access
of the base to H4, preventing proton abstraction at this
site.
9
q,r
lines.
Nevertheless, the yields of these reactions
remained limited (0–60%) due to the way the lithium
tri(aryl)magnesates were formed. Indeed, the bromine–
magnesium exchange used generated bromobutane,
To evaluate the scope of this reaction, it was next
extended to 2-fluoropyridine.
E
1
) 1/3 eq. Bu3MgLi
1) 1/3 eq. Bu MgLi
3
N
F
F
F
THF, -10 °C, 2 h
THF, -10 °C, 2 h
F
N
2) Electrophile
N
N
2)
3
) Hydrolysis
N
N
1
1
1
a: E= I, 64%
b: E= CH(OH)-4-anisyl, 50%
Br
1
e: 51%
c: E= CH(OH)-3,4,5-trimethoxyphenyl,
PdCl2(dppf) 1mol.%
reflux, 18 h
a
b
5
5% (74%) (60%)
d: E= CH2-CH=CH2, 40%
1
3
) Hydrolysis
a
Scheme 1. Reagents and conditions: Using 1/3equiv Bu
b
3
MgLi(TMEDA), THF, ꢀ10°C, 2h; Using 1equiv BuLi, 1equiv TMEDA, THF, ꢀ75°C,
2h.

H. Awad et al. / Tetrahedron Letters 45 (2004) 6697–6701
6699
-
F
N
F
F
Mg
N
1
) 1/3 eq. (TMP)3MgLi
Li+
N
N
F
Mg
F
THF, -10 °C, 2 h
N
N
N
N
2) I2 3) H2O
Li
N
F
F
2
: 66%
Scheme 2.
Lithiation of the substrate at C3 has been reported using
LDA, alkyllithiums being less efficient due to competi-
tive addition reactions. Various attempts to use lithium
1) 1/3 eq. Bu (TMP)MgLi
3
2
I
THF, -10 °C, 2 h
2
R
N
F
2) I2
R
N
F
trialkylmagnesates in THF at ꢀ10°C, with or without
TMEDA, were unsuccessful and the substrate was
recovered. Considering the migratory aptitude of TMP
3
: R= H, 84%
: R= F, 84%
4
6
over alkyl groups, lithium dialkyl(2,2,6,6-tetramethyl-
Scheme 3.
piperidino)magnesates were also tested, without success.
This could be justified by comparing the hydrogens total
atomic charges of the substrates (Table 1): the hydrogen
at C3 of 2-fluoropyridine is less acidic than the one at C4
of 3-fluoropyridine.
The hydrogen–magnesium exchange reaction was like-
wise effected with 1,3-difluorobenzene, and the magne-
sate formed intercepted to produce the expected iodide
2
2
5
Bu
3
a
(entry 1). In this case, the yield was similar using
MgLi (entry 2), and could be improved by adding
TMEDA (entry 3). The results are comparable to those
Since dilithium tetramethylzincate has been shown to
exhibit a higher reactivity compared to lithium trimeth-
ylzincate in various reactions including halogen–metal
2
2
obtained through lithiation using alkyllithiums. For
example, the reaction conducted using BuLi and 3,4,5-
1
8
exchange, we decided to turn to highly coordinated
magnesates and chose easily accessible dilithium tetr-
abutylmagnesate (Bu MgLi ).
2
3
trimethoxybenzaldehyde furnished the alcohol 5b in
a 81% yield (Table 2, entry 4).
4
2
No reaction was noted when 2-fluoropyridine was ex-
posed to 1/3equiv of Bu MgLi in THF at ꢀ10°C.
In conclusion, 3-fluoropyridine was deprotonated using
Bu
idyl)magnesate generated was either intercepted with
electrophiles or cross-coupled in a Ôone-potÕ procedure.
3-Fluoroquinoline was surprisingly deprotonated at C2
MgLi in THF at ꢀ10°C; the (3-fluoro-4-pyr-
4
2
3
Interestingly, the course of the reaction was completely
modified using a combination of Bu MgLi and HTMP
4
2
(
in a good yield. The same result was obtained with 2,6-
1/3equiv) followed by iodine to afford the compound 3
1
9
using (TMP) MgLi; the arylmagnesate could not be
3
2
0
difluoropyridine, giving the iodide 4 (Scheme 3).
intercepted with electrophiles but underwent a 1,2-
0
migration to afford the 2,2 -dimer after hydrolysis and
MgLi , when associated with HTMP
4 2
This result demonstrates the catalytic role of the amine
2
for the deprotonation.
autooxidation. Bu
(33mol%), proved to be more reactive for less activated
1
a
Table 1. Substrate hydrogenÕs total atomic charges
Substrate
23
4
5
6
7
8
F
0.225
0.237
0.222
0.208
N
F
0
.226
0.236
0.211
0.209
0.215
0.210
0.228
N
0
0
.232
.238
0.225
0.236
0.228
0.217
0.238
0.222
N
F
F
F
N
F
F
0
.244
0.228
a
The total atomic charges were determined by ab initio calculations using Gaussian 94 at the HF/6-31G(d) level after energy minimization using
cvff-300-1.01 (Cerius24.9).

6700
H. Awad et al. / Tetrahedron Letters 45 (2004) 6697–6701
Table 2. Deprotonation of 1,3-difluorobenzene using lithium magnesates
E
1
) base
F
F
F
F
a
THF, -10 °C, 2 h
2
) Electrophile
3
) Hydrolysis
5a,b
Entry
1
Base
Electrophile
E
Product
Yield (%)
1/3equiv Bu
3
3
3
(TMP)MgLi
MgLi
2
I
2
I
5a
5b
5b
5b
73
74
86
81
2
3
4
1/3equiv Bu
3,4,5-Trimethoxybenzaldehyde
3,4,5-Trimethoxybenzaldehyde
3,4,5-Trimethoxybenzaldehyde
CH(OH)-3,4,5-Trimethoxyphenyl
CH(OH)-3,4,5-Trimethoxyphenyl
CH(OH)-3,4,5-Trimethoxyphenyl
1/3equiv Bu
MgLi(TMEDA)
1equiv BuLi
a
ꢀ75°C using BuLi.
substrates such as 2-fluoropyridine. 1,3-Difluorobenzene
reacted similarly when treated with Bu MgLi; the reac-
ker, J.; Huth, A.; Ottow, E.; Mulzer, J. Tetrahedron 1995,
1, 9531–9542.
5
3
6
. (a) Kondo, Y.; Shilai, M.; Uchiyama, M.; Sakamoto, T. J.
Am. Chem. Soc. 1999, 121, 3539–3540; (b) Imahori, T.;
Uchiyama, M.; Sakamoto, T.; Kondo, Y. Chem. Com-
mun., 2001, 2450–2451; (c) Schwab, P. F. H.; Fleischer, F.;
Michl, J. J. Org. Chem. 2002, 67, 443–449; Concerning the
deprotonation of substituted benzenes, see: (d) Uchiyama,
M.; Miyoshi, T.; Kajihara, Y.; Sakamoto, T.; Otani, Y.;
Ohwada, T.; Kondo, Y. J. Am. Chem. Soc. 2002, 124,
tivity of the base proved to be enhanced by the presence
of TMEDA. The results suggest that the mechanism
does not proceed via aryllithiums species, since these
are not stable at ꢀ10°C, but via arylmagnesates. In
addition, Bu MgLi is assumed to be the reactive species
3
since Bu Mg does not allow deprotonation and BuLi
2
adds easily to azine rings.
8
514–8515.
7. Wittig, G.; Meyer, F. J.; Lange, G. Liebigs Ann. Chem.
951, 571, 167–201.
. For a synopsis, see: Mulvey, R. E. Chem. Commun. 2001,
049–1056.
. (a) Ashby, E. C.; Chao, L.-C.; Laemmle, J. J. Org. Chem.
974, 39, 3258–3263; (b) Kamienski, C. W.; Gastonia, N.
The main advantage of this methodology is the relative
stability of the organometallic species formed: hydro-
gen–lithium exchange has to be performed at low tem-
perature (ꢀ75°C) in order to prevent side reactions
such as nucleophilic additions or elimination of lithium
fluoride while hydrogen–magnesium exchange proceeds
at ꢀ10°C.
1
8
9
1
1
C.; Eastham, J. F. U.S. Patent 3,847,883, 1974; Chem.
Abstr. 1975, 82, 58590; (c) Richey, H. G., Jr.; Farkas, J.,
Jr. Tetrahedron Lett. 1985, 26, 275–278; (d) Richey, H. G.,
Jr.; Farkas, J., Jr. Organometallics 1990, 9, 1778–1784; (e)
Castaldi, G.; Borsotti, G. Eur. Pat. Appl. EP 491,326;
Chem. Abstr. 1992, 117, 150667; (f) Yasuda, M.; Ide, M.;
Matsumoto, Y.; Nakata, M. Synlett 1997, 899–902; (g)
Yasuda, M.; Ide, M.; Matsumoto, Y.; Nakata, M. Bull.
Chem. Soc. Jpn. 1998, 71, 1417–1429; (h) Ide, M.; Yasuda,
M.; Nakata, M. Synlett 1998, 936–938; (i) Kitagawa, K.;
Inoue, A.; Shinokubo, H.; Oshima, K. Angew. Chem., Int.
Ed. 2000, 39, 2481–2483; (j) Iida, T.; Wada, T.; Mase, T.
Japan Application No. JP 2000–024613 20000202, 2000;
Chem. Abstr. 2001, 135, 152370 Chem. Abstr. 2001, 135,
152370; (k) Kondo, J.; Inoue, A.; Shinokubo, H.; Oshima,
K. Angew. Chem., Int. Ed. 2001, 40, 2085–2087; (l) Inoue,
A.; Kitagawa, K.; Shinokubo, H.; Oshima, K. J. Org.
Chem. 2001, 66, 4333–4339; (m) Iida, T.; Wada, T.;
Tomimoto, K.; Mase, T. Tetrahedron Lett. 2001, 42,
4841–4844; (n) Inoue, A.; Kondo, J.; Shinokubo, H.;
Oshima, K. Chem. Eur. J. 2002, 8, 1730–1740; (o)
Fukuhara, K.; Takayama, Y.; Sato, F. J. Am. Chem.
Soc. 2003, 125, 6884–6885; (p) Dumouchel, S.; Mongin,
F.; Tr e´ court, F.; Qu e´ guiner, G. Tetrahedron Lett. 2003,
44, 2033–2035; (q) Dumouchel, S.; Mongin, F.; Tr e´ court,
F.; Qu e´ guiner, G. Tetrahedron Lett. 2003, 44, 3877–3880;
(r) Dumouchel, S.; Mongin, F.; Tr e´ court, F.; Qu e´ guiner,
G. Tetrahedron 2003, 59, 8629–8640; (s) Farkas, J., Jr.;
Stoudt, S. J.; Hanawalt, E. M.; Pajerski, A. D.; Richey, H.
G., Jr. Organometallics 2004, 23, 423–427; (t) Ito, S.;
Kubo, T.; Morita, N.; Matsui, Y.; Watanabe, T.; Ohta,
A.; Fujimori, K.; Murafuji, T.; Sugihara, Y.; Tajiri, A.
Tetrahedron Lett. 2004, 45, 2891–2894.
Deprotonation using Bu MgLi, typical procedure: BuLi
3
(
6.0mmol) was added to a solution of MgBr (2.0mmol)
2
in THF (3mL) at ꢀ10°C. After stirring for 1h at
10°C, 3-fluoropyridine (0.52mL, 6.0mmol) was intro-
duced at ꢀ30°C. After 2h at ꢀ10°C, a solution of I
ꢀ
2
(
1.5g, 6.0mmol) in THF (3mL) was added and the mix-
ture was stirred for 18h at rt. Addition of water (0.5mL)
and Na S O (until bleaching), dilution with CH Cl
2
2
2
3
2
(
phy using CH Cl as an eluent afforded compound 1a
50mL), drying over MgSO and column chromatogra-
4
2
2
(
64% yield).
References and notes
1
. Katritzky, A. R.; Rees, C. W. Boulton, A. J., McKillop,
A., Eds.; Comprehensive Heterocyclic Chemistry; Perga-
mon: Oxford, 1984; Vol. 2.
2
. (a) Qu e´ guiner, G.; Marsais, F.; Snieckus, V.; Epsztajn, J.
Adv. Heterocycl. Chem. 1991, 52, 187–304; (b) Mongin, F.;
Qu e´ guiner, G. Tetrahedron 2001, 57, 4059–4090; (c)
Turck, A.; Pl e´ , N.; Mongin, F.; Qu e´ guiner, G. Tetrahe-
dron 2001, 57, 4489–4505.
3
4
. Stanforth, S. P. Tetrahedron 1998, 54, 263–303.
. (a) Schlecker, W.; Huth, A.; Ottow, E.; Mulzer, J. J. Org.
Chem. 1995, 60, 8414–8416; (b) Schlecker, W.; Huth, A.;
Ottow, E.; Mulzer, J. Liebigs Ann., 1995, 1441–1446; (c)
Schlecker, W.; Huth, A.; Ottow, E.; Mulzer, J. Synthesis
1995, 1225–1227.
5
. (a) Bonnet, V.; Mongin, F.; Tr e´ court, F.; Qu e´ guiner, G. J.
Chem. Soc., Perkin Trans. 1, 2000, 4245–4249; (b) Schlec-
10. Armstrong, D. R.; Kennedy, A. R.; Mulvey, R. E.;
Rowlings, R. B. Angew. Chem., Int. Ed. 1999, 38, 131–133.

H. Awad et al. / Tetrahedron Letters 45 (2004) 6697–6701
6701
1
1
1
1. Compound 1a: mp 90°C. The physical and spectral data
are identical to those described: Rocca, P.; Marsais, F.;
Godard, A.; Qu e´ guiner, G. Tetrahedron 1993, 49, 49–64,
17. Compound 2: mp 149°C; H NMR (CDCl
1H, J = 8.3), 7.98 (dd, 1H, J = 5.3, 3.8), 7.89 (d, 1H,
3
): 8.30 (d,
J = 7.9), 7.75 (td, 1H, J = 7.1, 1.1), 7.65 (t, 1H,
J = 7.5); C NMR (CDCl ): 154.5 (dd, J = 262, 1.8),
3
144.8 (m, 2C), 129.5 (s), 128.6 (s), 128.6 (s), 127.8 (s), 126.6
(s), 119.2(m); IR (KBr): 3061, 29 69, 1613, 1496, 1453,
1414, 1355, 1340, 1326, 1316, 1216, 1157, 1141, 895, 780,
1
3
13
C NMR (CDCl
37.1 (d, J = 26), 133.7 (s), 92.4 (d, J = 23).
3
): 159.1 (d, J = 256), 145.6 (d, J = 5.1),
1
1
2. Compound 1b: mp 145°C; H NMR (CDCl
J = 4.9), 8.35 (s, 1H), 7.63 (t, J = 5.7, 1H), 7.30 (d, J = 8.3,
H), 6.88 (d, J = 8.7, 2H), 6.07 (s, 1H), 3.79 (s, 3H), 2.37
3
): 8.44 (d, 1H,
ꢀ
1
2
(
751cm .
1
3
s, 1H); C NMR (DMSO-d
J = 253), 146.4 (s), 141.4 (s), 137.6 (d, J = 20), 135.3 (s),
28.1 (s), 122.3 (d, J = 32), 114.1 (s), 67.6 (s), 55.3 (s); IR
KBr): 3138, 3006, 2838, 1611, 1510, 1260, 1067, 1032,
6
): 159.0 (s), 156.5 (d,
18. Uchiyama, M.; Kameda, M.; Mishima, O.; Yokoyama,
N.; Koike, M.; Kondo, Y.; Sakamoto, T. J. Am. Chem.
Soc. 1998, 120, 4934–4946.
19. Compound 3: mp < 50°C. The physical and spectral data
are identical to those described: Estel, L.; Marsais, F.;
Qu e´ guiner, G. J. Org. Chem. 1988, 53, 2740–2744.
NMR (CDCl ): 161.2(d, J = 233), 149.6 (d, J = 2.9), 146.6
(d, J = 13), 122.4 (d, J = 4.3), 75.8 (d, J = 43).
20. Compound 4: colourless oil; H NMR (CDCl
1
(
8
(
(
(
ꢀ
1
1
03cm . Compound 1c: mp 124–125°C; H NMR
CDCl ): 8.37 (d, 1H, J = 4.9), 8.32(d, 1H, J = 1.5), 7.58
t, 1H, J = 5.6), 6.60 (s, 2H), 6.03 (s, 1H), 3.81 (s, 6H), 3.80
s, 3H), 2.16 (s, 1H); C NMR (CDCl ): 156.4 (d,
1
3
C
3
3
1
3
3
1
J = 256), 153.2 (s, 2C), 145.7 (d, J = 5.1), 140.0 (d, J = 11),
3
): 8.20 (q,
1
3
1
1
37.4 (d, J = 25), 137.3 (s), 137.2 (s), 121.4 (d, J = 1.5),
03.1 (s, 2C), 68.7 (d, J = 1.4), 60.7 (s), 55.9 (s, 2C); IR
1H, J = 7.9), 6.70 (dd, 1H, J = 8.3, 2.6); C NMR
(CDCl ): 160.6 (m, 2C), 153.4 (dd, J = 7.4, 2.9), 108.2
(dd, J = 35, 5.9), 69.1 (dd, J = 41, 5.9); IR (KBr): 3093,
2928, 1595, 1568, 1449, 1425, 1407, 1398, 1377, 1302, 1268,
998, 816cm
3
(
KBr): 3181, 2838, 1590, 1509, 1494, 1464, 1419, 1322,
ꢀ1
1
3. Compound 1d: colourless oil; H NMR (CDCl ): 8.39 (s,
233, 1230, 1068, 1010, 810, 664cm
.
1
ꢀ1
1
.
3
1
1
H), 8.33 (d, 1H, J = 4.5), 7.17 (t, 1H, J = 5.7), 5.93 (m,
H), 5.16 (m, 2H), 3.44 (d, 2H, J = 6.8); C NMR
21. Diisopropylamine acts as a catalyst for the deprotonation
of arenes with alkyl and aryllithiums: Mallet, M. J.
Organomet. Chem. 1991, 406, 49–56.
22. (a) Compound 5a: colourless oil. The physical and spectral
data are identical to those described: Roe, A. M.; Burton,
M. A.; Willey, G. L.; Baines, M. W.; Rasmussen, A. C. J.
Med. Chem. 1968, 11, 814–819; (b) Rausis, T.; Schlosser,
M. Eur. J. Org. Chem. 2002, 3351–3358, IR (KBr): 2956,
1
3
(CDCl ): 158.0 (d, J = 254), 145.4 (d, J = 5.1), 137.5 (d,
3
J = 25), 135.5 (d, J = 14), 133.3 (s), 124.8 (d, J = 1.5),
117.6 (s), 32.0 (d, J = 2.9); IR (KBr): 2956, 2359, 1586,
1551, 1438, 1297, 1155, 1126, 980, 785cm
ꢀ1
.
1
1
4. Compound 1e: mp < 50°C; H NMR (CDCl ): 8.77 (d,
3
1
7
H, J = 4.1), 8.57 (d, 1H, J = 2.6), 8.53 (d, 1H, J = 4.9),
.99 (t, 1H, J = 5.8), 7.90 (d, 1H, J = 7.9), 7.82(t, 1H,
2927, 2857, 1626, 1591, 1463, 1431, 1284, 1235, 990, 777,
691, 561cm
1
3
ꢀ1
J = 7.2), 7.36 (t, 1H, J = 6.0); C NMR (CDCl ): 156.4 (d,
3
.
1
J = 257), 149.7 (d, J = 2.9), 149.4 (s), 145.4 (d, J = 5.1),
138.5 (d, J = 27), 136.1 (s), 133.1 (d, J = 8.7), 124.3 (d,
J = 10), 123.4 (s), 123.3 (s); IR (KBr): 3408, 3054, 1587,
23. Compound 5b: mp 94–95°C; H NMR (CDCl ): 7.26
3
(quint., 1H, J = 7.0), 6.91 (t, 2H, J = 8.1), 6.63 (s,
2H), 6.16 (d, 1H, J = 8.3), 3.82(s, 9H), .28 6 (d, 1H,
ꢀ1
13
J = 8.3); C NMR (CDCl ): 160.3 (dd, J = 249, 8.7, 2C),
1
574, 1488, 1463, 1435, 1415, 1263, 1204, 1053, 798cm
5. Roe, A.; Hawkins, G. F. J. Am. Chem. Soc. 1949, 71,
785–1786.
.
3
1
1
152.7 (s, 2C), 137.8 (s), 136.6 (s), 129.1 (t, J = 11), 119.1 (t,
J = 16), 111.5 (m, 2C), 102.3 (s, 2C), 66.8 (s), 60.3 (s), 55.6
(s, 2C); IR (KBr): 3420, 2975, 2940, 2845, 1623, 1595,
1504, 1471, 1414, 1332, 1233, 1126, 1075, 992, 818, 793,
1
6. Drewette, K. J.; Henderson, K. W.; Kennedy, A. R.;
Mulvey, R. E.; OÕHara, C. T.; Rowlings, R. B. Chem.
Commun. 2002, 1176–1177.
ꢀ
1
.
780cm