Synthesis and deprotonation of 2-(halophenyl)pyridines and 1-(halophenyl)isoquinolines

Article abstract of DOI:10.1021/jo049454v

The ability of the 2-pyridyl and 1-isoquinolyl groups to direct metalation was studied in the benzene series. For this purpose, 2-(halophenyl)pyridines and 1-(halophenyl)isoquinolines were prepared. Interestingly, nucleophilic addition reactions on the azine ring were not observed under kinetic control using butyllithium, and the substrates were cleanly deprotonated on the benzene ring: the azine ring acidifies the adjacent hydrogen H₂ (N-H₂ interaction through space and/or inductive electron-withdrawing effect) and probably favors the approach of butyllithium (chelation). Under thermodynamic conditions using lithium dialkylamides, the presence of the azine group makes the lithio derivative at C2′ more stable (chelation and/or inductive electron-withdrawing effect). This was evidenced in two ways: (1) syntheses of 2-halophenyllithiums (F, Cl, Br) substituted at C6 by a 2-pyridyl or 1-isoquinolyl group without elimination of lithium halide and (2) iodine migration from C2′ to C4′ when treating 2-(3-halo-2-iodophenyl) pyridines or 1-(3-fluoro-2-iodophenyl)isoquinoline with LTMP. Comparisons between the 2-pyridyl and fluoro units showed the latter was the stronger directing group for deprotonation.

Full text of DOI:10.1021/jo049454v

Syn th esis a n d Dep r oton a tion of 2-(Ha lop h en yl)p yr id in es a n d
1-(Ha lop h en yl)isoqu in olin es
Florence Mongin,* Anne-Sophie Rebstock, Franc¸ois Tre´court, Guy Que´guiner, and
Francis Marsais
Laboratoire de Chimie Organique Fine et He´te´rocyclique, UMR 6014, IRCOF, Place E. Blondel,
BP 08, 76131 Mont-Saint-Aignan Ce´dex, France
florence.mongin@insa-rouen.fr
Received April 2, 2004
The ability of the 2-pyridyl and 1-isoquinolyl groups to direct metalation was studied in the benzene
series. For this purpose, 2-(halophenyl)pyridines and 1-(halophenyl)isoquinolines were prepared.
Interestingly, nucleophilic addition reactions on the azine ring were not observed under kinetic
control using butyllithium, and the substrates were cleanly deprotonated on the benzene ring: the
azine ring acidifies the adjacent hydrogen H2′ (N-H2′ interaction through space and/or inductive
electron-withdrawing effect) and probably favors the approach of butyllithium (chelation). Under
thermodynamic conditions using lithium dialkylamides, the presence of the azine group makes
the lithio derivative at C2′ more stable (chelation and/or inductive electron-withdrawing effect).
This was evidenced in two ways: (1) syntheses of 2-halophenyllithiums (F, Cl, Br) substituted at
C6 by a 2-pyridyl or 1-isoquinolyl group without elimination of lithium halide and (2) iodine
migration from C2′ to C4′ when treating 2-(3-halo-2-iodophenyl)pyridines or 1-(3-fluoro-2-iodophen-
yl)isoquinoline with LTMP. Comparisons between the 2-pyridyl and fluoro units showed the latter
was the stronger directing group for deprotonation.
In tr od u ction
at the 3′ position is abstracted using butyllithium in THF
at 0 °C, the deprotonation occurs at the 5′ position using
tert-butyllithium in diethyl ether at -70 °C (a); the latter
result can be attributed to a coordination between the
ring nitrogen and the base lithium before deprotonation.3
The lithiation of 2-(3-thienyl)pyridine at the 2′ position
using butyllithium in diethyl ether was reported in 1990
(b); in this case, both chelation before deprotonation and
the acidifying effect of the 2-pyridyl group could be
responsible for the result observed.4 In 1996, the 2-pyridyl
group was exploited in the reactions of 2,2′- and 2,4′-
bipyridines using LTMP in THF at -40 or -70 °C (c).5
The medium to good yields obtained could be due to the
nature of the electrophiles used, which prefer to trap the
aryllithium before the lithium amide (note the presence
of disubstituted products at C3 and C3′ starting from 2,2′-
bipyridine), allowing the lithiation equilibrium to be
displaced toward the deprotonated product. Nevertheless,
the 2-pyridyl group favors the deprotonation since bare
pyridine can hardly be deprotonated at C3.2 Selective
deprotonation of 2-chloro-6-phenylpyridine at the 2′
position using tert-butyllithium in a mixture of diethyl
ether and cumene at -75 °C was published recently (d),6
a result due to interactions between the 6-chloro-2-
pyridyl unit and the lithium of the base before deproto-
The directed ortho-metalation plays an important role
in the modern organic synthesis.1,2 Despite the maturity
gained by the method since its creation, the way a
substituent acts in its vicinity remains somewhat mis-
understood.
A heteroatom-containing unit (known as the directed
metalation group, DMG) makes the deprotonation pro-
cess easier by coordinating the base; it also stabilizes the
lithio derivative by chelation. In addition, an electron-
withdrawing DMG favors the deprotonation in its envi-
ronment (mostly at the ortho position) and reinforces the
stabilization of the lithio derivative.
The 2-pyridyl group has been shown to direct ortho-
lithiation in a few examples. Its effect on aromatic
deprotonation was evidenced in the course of the reaction
of 2-(2-thienyl)pyridine (Chart 1): whereas the hydrogen
* To whom correspondence should be addressed. Phone: + 33 (0) 2
35 52 24 82. Fax: + 33 (0) 2 35 52 29 62.
(1) The concept emerged from the systematic studies of Gilman,
Wittig and Hauser, and found numerous disciples, notably Gschwend,
Beak, and Snieckus: (a) Gilman, H.; Bebb, R. L. J . Am. Chem. Soc.
1939, 61, 109-112. (b) Wittig, G.; Fuhrmann, G. Chem. Ber. 1940, 73,
3B, 1197-1218. (c) Hauser, C. R.; Puterbaugh, W. H. J . Org. Chem.
1964, 29, 853-856. (d) Gschwend, H. W.; Rodriguez, H. R. Org. React.
1979, 26, 1-360. (e) Snieckus, V. Chem. Rev. 1990, 90, 879-933. (f)
Anderson, D. R.; Faibish, N. C.; Beak, P. J . Am. Chem. Soc. 1999, 121,
7553-7558.
(3) Kauffmann, T.; Mitschker, A.; Woltermann, A. Chem. Ber. 1983,
116, 992-1000.
(2) In the π-deficient azaaromatics series, see: (a) Que´guiner, G.;
Marsais, F.; Snieckus, V.; Epsztajn, J . Adv. Heterocycl. Chem. 1991,
52, 187-304. (b) Mongin, F.; Que´guiner, G. Tetrahedron 2001, 57,
4059-4090. (c) Turck, A.; Ple´, N.; Mongin, F.; Que´guiner, G. Tetra-
hedron 2001, 57, 4489-4505.
(4) Kumar Das, V. G.; Mun, L. K.; Wei, C.; Mak, T. C. W.
Organometallics 1987, 6, 10-14.
(5) Zoltewicz, J . A.; Dill, C. D. Tetrahedron 1996, 52, 14469-14474.
(6) Fort, Y.; Rodriguez, A. L. J . Org. Chem. 2003, 68, 4918-4922.
10.1021/jo049454v CCC: $27.50 © 2004 American Chemical Society
Published on Web 08/31/2004
6766
J . Org. Chem. 2004, 69, 6766-6771

Deprotonation of 2-(Halophenyl)pyridines and 1-(Halophenyl)isoquinolines
CHART 1
SCHEME 1
TABLE 1. Dep r oton a tion of 2-(3-Ha lop h en yl)p yr id in es
1-3
nation. It represents the only example of benzene ortho-
lithiation directed by a 2-pyridyl group.
Resu lts a n d Discu ssion
Since biphenyl is ortho-metalated in high proportions,7
one can wonder what the changes will be if one phenyl
is replaced by a 2-pyridyl (or 1-isoquinolyl). The total
atomic charges of biphenyl, 2-phenylpyridine, and 1-phen-
ylisoquinoline were determined by ab initio calculations
using Gaussian 94 at the HF/6-31G(d) level after energy
minimization using cvff-300-1.01 (Cerius2 4.9).8 Values
of 0.245 or 0.222 for the hydrogens at the position 2′- of
2-phenylpyridine or 1-phenylisoquinoline, respectively,
were determined. This shows the nitrogenous groups
exhibit an acidifying effect, since 0.208 was found for the
hydrogen at C2 in biphenyl. Partly because it is out of
the plane of the phenyl ring,9 the 1-isoquinolyl group
effect on the acidity of H2′ is weaker.
Deprotonation of 2-phenylpyridine was attempted by
Gros and Fort under various conditions (lithium dialkyl-
amides or alkyllithiums, with or without additive, in
ethereal or hydrocarbon solutions):10 the substrate either
undergoes 1,2-addition of alkyllithiums in ethereal sol-
vents, or deprotonation at C2 using the BuLi-LiDMAE
superbase in hexane. To promote deprotonation at the
phenyl group, we introduced a second ortho-directing
group, in this case a halo group, at the 3′ position of
2-phenylpyridine or 1-phenylisoquinoline.
entry
substrate
product
yield (%)
1a
2a
3a
4a
5d
6d
1 (R ) F)
1 (R ) F)
2 (R ) Cl)
2 (R ) Cl)
2 (R ) Cl)
3 (R ) Br)
7a (El ) D)b
7b (El ) I)c
8a (El ) D)b
8b (El ) I)c
8a (El ) D)b
9 (El ) D)b
88
66
76
62
42
29
a
b
The base is BuLi (1 equiv). The electrophile is D2O. c The
d
electrophile is I2. The base is LTMP (2 equiv).
2-halopyridine, or 1-chloroisoquinoline, and halophenyl-
boronic acid, using standard conditions11 (Scheme 1).
Deprotonation of the 2-(3-halophenyl)pyridines 1-3
was first considered. Even if alkyllithiums are renowned
for facile nucleophilic additions to the CdN bond of
pyridines,2 their use was attempted to deprotonate the
fluoride 1 and the chloride 2. Indeed, the metalations of
fluorobenzene and chlorobenzene have been reported
using such bases.12,13
The fluoride 1 was easily deprotonated at C2′ using 1
equiv of butyllithium in THF at -75 °C, and the lithio
intermediate was intercepted with D2O or iodine to give
the compounds 7a ,b in good yields (Table 1, entries 1 and
2). Note that a mixture of butyllithium and potassium
tert-butoxide also furnished 7a (75% yield) together with
a little amount of degradation compounds. When com-
pared with the metalation of fluorobenzene, which re-
quires a 7 h contact with butyllithium in THF at -50
The starting biaryl substrates 1-6 were synthesized
by Suzuki cross-coupling reactions between the required
(7) Neugebauer, W.; Kos, A. J .; Schleyer, P. V. R. J . Organomet.
Chem. 1982, 228, 107-118.
(8) Note that the data probe ground states rather than transition
states, but even the use of more extended basis sets would not have
guaranteed meaningful results.
(9) Energy minimization using cvff-300-1.01 (Cerius2 4.9) shows the
more stable conformation of 1-phenylisoquinoline has a dihedral angle
of 45°; the energy increases by about 1000 kcal‚mol-1 when the
1-isoquinolyl ring is kept in the phenyl plane. On the other hand, the
more stable conformation of 2-phenylpyridine is planar.
(10) Gros, P.; Fort, Y. J . Org. Chem. 2003, 68, 2028-2029.
(11) Alcock, N. W.; Brown, J . M.; Hulmes, D. I. Tetrahedron:
Asymmetry 1993, 4, 743-756.
(12) Gilman, H.; Soddy, T. S. J . Org. Chem. 1957, 22, 1715-1716.
(13) Iwao, M. J . Org. Chem. 1990, 55, 3622-3627.
J . Org. Chem, Vol. 69, No. 20, 2004 6767

Mongin et al.
SCHEME 2
°C,12 the reaction involving the fluoride 1 is particularly
facile. Both the ability of the 2-pyridyl group to coordinate
the lithiating agent and the acidifying effect of the
nitrogenous DMG may be suggested to explain the
regioselectivities observed.
(LICKOR),19 under the conditions reported for deproto-
nating fluorobenzene,20 finally ensured a clean metalation
of 10 at the 3′ position. As intramolecular competition of
ortho-directing groups sometimes gives treacherous re-
sults, the 2-pyridyl and fluoro groups were better com-
pared using an intermolecular competition experiment.21
Under the conditions used for the deprotonation of the
fluoride 10, an equimolar mixture of 2-phenylpyridine
and fluorobenzene afforded 2-fluorobenzoic acid in 60%
yield (deprotonation of 2-phenylpyridine was not ob-
served), showing the 2-pyridyl group is not strong enough
to compete with a fluoro group.
Similarly, the chloride 2 furnished the compounds 8a ,b
in good yields (Table 1, entries 3 and 4). Other bases such
as sec-butyllithium or a mixture of butyllithium and
potassium tert-butoxide (LICKOR) were less effective or/
and gave nucleophilic addition compounds at C6. Whereas
2-chloro-1-lithiobenzene already provides benzyne at -75
°C,13 the reaction involving the chloride 2 was easily
conducted at this temperature. Stabilization of the lithio
derivative by chelation of the metal with the pyridine
nitrogen and/or inductive electron-withdrawing effect of
the 2-pyridyl group could in our case prevent the elimi-
nation of lithium chloride giving the aryne.14
Deprotonation occurred next to the fluoro group too
when the dihalide 11b was treated with LTMP at low
temperature,22 giving the trihalide 12 after trapping with
iodine (Scheme 2). In a recent publication, Schlosser
documented an iodine migration on 2-fluoro-1,3-diiodo-
benzene using LTMP, giving after the quenching step
with an electrophile 2-substituted 3-fluoro-1,4-diiodoben-
zenes.23 Nevertheless, the attempts to conduct such a
reaction with 12 failed: the latter either remained
unchanged or underwent deiodination reactions on ex-
posure to LTMP. A plausible assumption to explain
deiodination is SET from the base to the trihalide. The
radical anion thus generated eliminates lithium iodide
to produce an aryl radical. The latter may either abstract
a hydrogen atom from the solvent or absorb another
unpaired electron to give an aryllithium species to be
quenched by the free amine or to survive until electro-
Since alkyllithiums cannot be used in the presence of
bromine atoms, the deprotonation of the bromide 3 was
attempted using LTMP (pKa of 2,2,6,6-tetramethylpip-
eridine: 37.3),15 a lithium amide more basic than LDA
(pKa of diisopropylamine: 35.7).15 Interestingly, the
bromide 3 was deprotonated on exposure to 2 equiv of
LTMP in THF at -75 °C, as demonstrated by deuteri-
olysis to afford 9 (Table 1, entry 6). The yield of 29% is
low, certainly, but the result is unprecedented since
deprotonation of bromobenzene has never been achieved
before, probably due to decomposition giving benzyne
under metalation conditions. Indeed, whereas 2-fluoro-
and 2-chlorophenyllithium are stable at -75 and -90 °C,
respectively, 2-bromophenyllithium (all are generated
through bromine-lithium exchange) already decomposes
at -100 °C.16 Elimination of lithium bromide is prevented
here, a consequence of the stabilizing effect the nitrogen
exerts. Note that under the same conditions, the chloride
2 furnished the deuterated compound 8a in 42% yield,
showing only a little difference between both halogens17
(Table 1, entry 5).
(14) The good stabilities of lithium 2-lithio-3-chlorobenzoate and
lithium 2-lithio-3-bromobenzoate toward elimination of lithium halide
were similarly attributed to the chelation of lithium with the adjacent
group, in this case the carboxylate moiety: Gohier, F.; Mortier, J . J .
Org. Chem. 2003, 68, 2030-2033.
(15) Fraser, R. R.; Mansour, T. S. J . Org. Chem. 1984, 49, 3442-
3443.
(16) Gilman, H.; Gorsich, R. D. J . Am. Chem. Soc. 1956, 78, 2217-
2222.
(17) Mongin, F.; Schlosser, M. Tetrahedron Lett. 1997, 38, 1559-
1562.
(18) Concerning Kharasch cross-coupling reactions between aryl-
magnesium halides and aryl chlorides under nickel catalysis, see: (a)
Sengupta, S.; Leite, M.; Raslan, D. S.; Quesnelle, C.; Snieckus, V. J .
Org. Chem. 1992, 57, 4066-4068. (b) Bo¨hm, V. P. W.; Weskamp, T.;
Gsto¨ttmayr, C. W. K.; Herrmann, W. A. Angew. Chem., Int. Ed. 2000,
39, 1602-1604. (c) Bonnet, V.; Mongin, F.; Tre´court, F.; Breton, G.;
Marsais, F.; Knochel, P.; Que´guiner, G. Synlett 2002, 1008-1010.
(19) (a) Schlosser, M. J . Organomet. Chem. 1967, 8, 9-16. (b)
Lochmann, L. Eur. J . Inorg. Chem. 2000, 7, 1115-1126.
(20) Schlosser, M.; Katsoulos, G.; Takagishi, S. Synlett 1990, 747-
748.
To compare the 2-pyridyl and fluoro groups, the
fluoride 10 was prepared by cross-coupling reaction
between 4-fluorophenylmagnesium bromide and 2-chlo-
ropyridine under nickel catalysis18 and submitted to the
deprotonation procedure. The reaction was first at-
tempted using various butyllithiums (with or without
TMEDA) without success: the starting substrate was
recovered when the reaction was conducted at -75 °C,
and nucleophilic addition compounds at C6 were obtained
at higher temperatures. Having recourse to the super-
basic mixture of butyllithium and potassium tert-butoxide
(21) Schlosser, M., Ed. In Organometallics in Synthesis: A Manual;
Wiley: Chichester, 1994 (1st ed.) and 2002 (2nd ed.).
(22) 1-Fluoro-2-iodobenzene was also deprotonated next to the fluoro
group using LDA: Bridges, A. J .; Lee, A.; Maduakor, E. C.; Schwartz,
C. E. Tetrahedron Lett. 1992, 33, 7499-7502.
(23) Rausis, T.; Schlosser, M. Eur. J . Org. Chem. 2002, 3351-3358.
6768 J . Org. Chem., Vol. 69, No. 20, 2004

Deprotonation of 2-(Halophenyl)pyridines and 1-(Halophenyl)isoquinolines
SCHEME 3
SCHEME 5
SCHEME 4
SCHEME 6
Con clu sion s
philic trapping.24 Iodine being less acidifying than bro-
mine, deprotonation in its immediate vicinity occurs even
more slowly and is not detected.
The ability of the 2-pyridyl and 1-isoquinolyl groups
to direct metalation was studied in the benzene series.
For this purpose, 2-(halophenyl)pyridines and 1-(halophe-
nyl)isoquinolines were prepared. Interestingly, nucleo-
philic addition reactions on the azine ring were not
observed under kinetic control using butyllithium, and
the substrates were cleanly deprotonated on the benzene
ring: the azine ring acidifies the adjacent hydrogen H2′
(N-H2′ interaction through space and/or inductive elec-
tron-withdrawing effect) and probably favors the ap-
proach of butyllithium (chelation). Under thermodynamic
conditions using lithium dialkylamides,26 the presence
of the azine group makes the lithio derivative at C2′ more
stable (chelation and/or inductive electron-withdrawing
effect). This was evidenced in two ways: (1) syntheses
of 2-halophenyllithiums (F, Cl, Br) substituted at C6 by
a 2-pyridyl or 1-isoquinolyl group without elimination of
lithium halide and (2) iodine migration from C2′ to C4′
when treating 2-(3-halo-2-iodophenyl)pyridines or 1-(3-
fluoro-2-iodophenyl)isoquinoline with LTMP. Compari-
sons between the 2-pyridyl and fluoro units showed the
latter was the stronger directing group for deprotonation.
Further investigations to extend the scope of this
reaction to the syntheses of chiral ligands are currently
in progress.
On the other hand, leading the reaction on the diha-
lides 7b and 8b resulted in the compounds 13 and 14
after deuteriolysis. Deprotonation at C4′ generates first
a lithio derivative, which is next converted into a
thermodynamically more stable isomer through iodine
migration (Scheme 3). The halogen migration mechanism
has been the subject of several studies considering
halogen-rich species as intermediates.2 The halogen
transfer could be carried out via a hypervalent halogen
(ate) complex.25
The lower yield obtained for 14 can be partially
explained by competitive iodine loss.
Deprotonation of the 1-(3-halophenyl)isoquinolines 4
and 5 was next considered. As previously described for
the pyridine derivatives 1, the fluoride 4 was easily
deprotonated using 1 equiv of butyllithium in THF at
-75 °C, and the lithio intermediates were intercepted
with D2O or iodine to give the compounds 15a ,b in good
yields. The reaction is still regioselective at C2′. The
compounds 16a ,b were similarly generated, starting from
the chloride 5 (Scheme 4). Metalation of the latter was
additionally conducted using 2 equiv of LTMP in THF
at -75 °C; subsequent deuteriolysis afforded 16a (31%
yield), a result comparable to that obtained with 2.
With the difluoride 6, a comparison between the fluoro
and 1-isoquinolyl units is possible: the former exhibits
a stronger directing power, as demonstrated by trapping
with iodine or chlorotrimethylsilane to afford 17a ,b in
good yields (Scheme 5). All the attempts to make the
iodine of 17a migrate using LTMP were unsuccessful.
As described above in the pyridine series, metalation
of the dihalide 15b with LTMP promoted iodine migra-
tion to afford after quenching the deuterated product 18
(Scheme 6).
Exp er im en ta l Section
Gen er a l P r oced u r es. The NMR spectra were recorded in
CDCl3 (1H at 300 MHz and 13C at 75 MHz). Deuterium
incorporation was determined from the 1H NMR integration
values. The main IR absorptions of the IR spectra are given.
THF was distilled from benzophenone/Na. The water content
of the solvents was estimated to be lower than 45 ppm by the
modified Karl Fischer method.27 Metalation and cross-coupling
reactions were carried out under dry N2. Petrol refers to
petroleum ether (bp 40-60 °C). After the reaction, hydrolysis,
and neutralization, the aqueous solution was extracted several
times with CH2Cl2. The organic layer was dried over MgSO4,
the solvents were evaporated under reduced pressure, and
(24) Mongin, F.; Marzi, E.; Schlosser, M. Eur. J . Org. Chem. 2001,
2771-2777.
(25) Concerning the iodine transfer from iodobenzene to 2-lithio-
aromatics, see: Tripathy, S.; LeBlanc, R.; Durst, T. Org. Lett. 1999, 1,
1973-1975.
(26) Note that lithium dialkylamides sometimes give products from
kinetic control when used in the presence of an electrophile using
Barbier-type conditions.
(27) Bizot, J . Bull. Soc. Chim. Fr. 1967, 151.
J . Org. Chem, Vol. 69, No. 20, 2004 6769

Mongin et al.
unless otherwise noted, the crude compound was chromato-
graphed on a silica gel (Geduran Si 60, 0.063-0.200 mm)
column (the eluent is given in the product description). Pd-
(PPh3)4 was synthesized by a literature method.28 2-(3-Fluo-
rophenyl)pyridine (1),29 2-(3-chlorophenyl)pyridine (2),30 and
2-(4-fluorophenyl)pyridine (10)31 were previously described.
2-(3-Br om op h en yl)p yr id in e (3). A degassed mixture of
2-bromopyridine (0.96 mL, 10 mmol), Na2CO3 (2.3 g, 22 mmol),
water (11 mL), EtOH (8 mL), dimethoxyethane (25 mL),
3-bromophenylboronic acid (2.0 g, 10 mmol), and Pd(PPh3)4
(115 mg, 0.10 mmol) was heated at reflux for 18 h to afford
1.5 g (64%) of 3 (eluent: CH2Cl2): colorless oil; 1H and 13C
NMR data are in agreement with literature values;32 IR (KBr)
ν 3064, 3008, 1586, 1559, 1458, 1441, 1432, 1404, 1277, 785,
765, 673. Anal. Calcd for C11H8BrN (234.10): C, 56.44; H, 3.44;
N, 5.98. Found: C, 56.32; H, 3.51; N, 5.81.
(0.1 mL) to afford 0.16 g (96%, 92% d) of 7a (eluent: CH2Cl2).
The 1H and 13C NMR data of this product showed the
replacements of 2′-H by 2′-D and 2′-CH by 2′-CD, respectively.
2-(3-F lu or o-2-iod op h en yl)p yr id in e (7b). A solution of the
fluoride 1 (0.17 g, 1.0 mmol) in THF (3 mL) was successively
treated with BuLi (1.0 mmol) at -75 °C and, 1 h later, a
solution of iodine (0.25 g, 1.0 mmol) in THF (3 mL) to afford
0.20 g (66%) of 7b (eluent: CH2Cl2): pale yellow oil; 1H NMR
(CDCl3) δ 7.11 (td, 1H, J ) 8.0, 1.4 Hz), 7.25 (dd, 1H, J ) 7.9,
1.2 Hz), 7.34 (ddd, 1H, J ) 7.5, 4.9, 1.0 Hz), 7.39 (td, 1H, J )
7.9, 5.5 Hz), 7.50 (d, 1H, J ) 7.8 Hz), 7.80 (td, 1H, J ) 7.8, 1.8
Hz), 8.72 (d, 1H, J ) 4.9 Hz); 13C NMR (CDCl3) δ 84.9 (d, J )
26 Hz), 114.9 (d, J ) 25 Hz), 122.7, 124.3, 125.8 (d, J ) 2.9
Hz), 129.7 (d, J ) 8.5 Hz), 136.1, 147.1, 149.2, 159.6, 161.6 (d,
J ) 245 Hz); IR (KBr) ν 3392, 3063, 3008, 1584, 1563, 1455,
1436, 1416, 1242, 891, 775, 749. Anal. Calcd for C11H7FIN
(299.09): C, 44.18; H, 2.36; N, 4.68. Found: C, 44.28; H, 2.57;
N, 4.48.
1-(3-F lu or op h en yl)isoqu in olin e (4). A degassed mixture
of 1-chloroisoquinoline (1.6 g, 10 mmol), Na2CO3 (2.3 g, 22
mmol), water (11 mL), EtOH (8 mL), dimethoxyethane (25
mL), 3-fluorophenylboronic acid (1.4 g, 10 mmol), and Pd-
(PPh3)4 (115 mg, 0.10 mmol) was heated at reflux for 18 h to
afford 1.9 g (87%) of 4 (eluent: petrol/AcOEt 80:20): pale
2-(2-[2H]-3-ch lor op h en yl)p yr id in e (8a ). A solution of the
chloride 2 (0.19 g, 1.0 mmol) in THF (3 mL) was successively
treated with BuLi (1.0 mmol) at -75 °C and, 1 h later, D2O
(0.1 mL) to afford 0.18 g (95%, 80% d) of 8a (eluent: CH2Cl2/
AcOEt 95:5). The 1H and 13C NMR data of this product showed
the replacements of 2′-H by 2′-D and 2′-CH by 2′-CD, respec-
tively.
1
yellow oil; H NMR (CDCl3) δ 7.21 (m, 1H), 7.43 (d, 1H, J )
10 Hz), 7.5 (m, 3H), 7.7 (m, 2H), 7.91 (d, 1H, J ) 8.2 Hz), 8.09
(d, 1H, J ) 8.5 Hz), 8.61 (d, 1H, J ) 5.7 Hz); 13C NMR (CDCl3)
δ 115.5 (d, J ) 21 Hz), 116.9 (d, J ) 22 Hz), 120.3, 125.6 (d,
J ) 2.9 Hz), 126.4, 127.0, 127.0, 127.4, 129.8 (d, J ) 8.2 Hz),
130.1, 136.7, 141.6 (d, J ) 7.5 Hz), 142.1, 159.1, 162.6 (d, J )
246 Hz); IR (KBr) ν 3052, 1582, 1556, 1443, 1385, 1354, 1191,
2-(3-Ch lor o-2-iod op h en yl)p yr id in e (8b). A solution of the
chloride 2 (0.19 g, 1.0 mmol) in THF (3 mL) was successively
treated with BuLi (1.0 mmol) at -75 °C and, 1 h later, a
solution of iodine (0.25 g, 1.0 mmol) in THF (3 mL) to afford
0.20 g (62%) of 8b (eluent: CH2Cl2/AcOEt 95:5): pale yellow
899, 827, 799, 785, 752, 703. Anal. Calcd for
C15H10FN
1
(223.25): C, 80.70; H, 4.51; N, 6.27. Found: C, 80.68; H, 4.55;
N, 6.25.
oil; H NMR (CDCl3) δ 7.26 (dd, 1H, J ) 4.0, 1.8 Hz), 7.4 (m,
2H), 7.45 (d, 1H, J ) 7.8 Hz), 7.50 (dd, 1H, J ) 7.9, 1.6 Hz),
7.79 (td, 1H, J ) 7.7, 1.7 Hz), 8.71 (d, 1H, J ) 4.9 Hz); 13C
NMR (CDCl3) δ 101.6, 122.7, 124.2, 127.7, 128.8, 129.0, 136.1,
139.5, 148.3, 149.1, 161.2; IR (KBr) ν 3400, 3058, 3004, 1588,
1567, 1474, 1444, 1426, 1391, 774, 748, 712. Anal. Calcd for
1-(3-Ch lor op h en yl)isoqu in olin e (5). A degassed mixture
of 1-chloroisoquinoline (1.6 g, 10 mmol), Na2CO3 (2.3 g, 22
mmol), water (11 mL), EtOH (8 mL), dimethoxyethane (25
mL), 3-chlorophenylboronic acid (1.6 g, 10 mmol), and Pd-
(PPh3)4 (115 mg, 0.10 mmol) was heated at reflux for 18 h to
afford 2.2 g (92%) of 5 (eluent: petrol/AcOEt 80:20): pale
yellow oil; 1H NMR (CDCl3) δ 7.5 (m, 2H), 7.6 (m, 2H), 7.7 (m,
3H), 7.90 (d, 1H, J ) 8.2 Hz), 8.06 (d, 1H, J ) 8.4 Hz), 8.61 (d,
1H, J ) 5.7 Hz); 13C NMR (CDCl3) δ 120.2, 126.3, 126.8, 126.9,
127.3, 127.9, 128.5, 129.4, 129.8, 130.0, 134.2, 136.6, 141.1,
142.0, 158.8; IR (KBr) ν 3050, 1551, 1382, 1350, 881, 824, 804,
784, 752, 695, 668. Anal. Calcd for C15H10ClN (239.71): C,
75.16; H, 4.21; N, 5.84. Found: C, 75.19; H, 4.35; N, 5.62.
1-(3,5-Diflu or op h en yl)isoqu in olin e (6). A degassed mix-
ture of 1-chloroisoquinoline (1.6 g, 10 mmol), Na2CO3 (2.3 g,
22 mmol), water (11 mL), EtOH (8 mL), dimethoxyethane (25
mL), 3,5-difluorophenylboronic acid (1.6 g, 10 mmol), and Pd-
(PPh3)4 (115 mg, 0.10 mmol) was heated at reflux for 18 h to
afford 2.1 g (86%) of 6 (eluent: CH2Cl2/AcOEt 97.5:2.5): mp
100-102 °C; 1H NMR (CDCl3) δ 6.95 (t, 1H, J ) 8.8 Hz), 7.24
(m, 2H), 7.59 (t, 1H, J ) 7.6 Hz), 7.7 (m, 2H), 7.91 (d, 1H, J )
C
11H7ClIN (315.54): C, 41.87; H, 2.24; N, 4.44. Found: C,
41.68; H, 2.27; N, 4.38.
2-(2-[2H]-3-br om op h en yl)p yr id in e (9). A solution of the
bromide 3 (0.23 g, 1.0 mmol) in THF (2 mL) was added to a
solution of LTMP [obtained by adding BuLi (2.0 mmol) to a
solution of 2,2,6,6-tetramethylpiperidine (0.35 mL, 2.1 mmol)
in THF (2 mL) at 0 °C] at -75 °C. After 1 h at -75 °C,
deuteriolysis with D2O (0.2 mL) afforded 0.19 g (82%, 35% d)
of 9 (eluent: CH2Cl2). The 1H and 13C NMR data of this product
showed the replacements of 2′-H by 2′-D and 2′-CH by 2′-CD,
respectively.
2-(3-[2H ]-4-flu or op h en yl)p yr id in e (11a ). A solution of
the fluoride 10 (0.17 g, 1.0 mmol) and potassium tert-butoxide
(0.11 g, 1.0 mmol) in THF (3 mL) was treated with BuLi (1.0
mmol) at -75 °C. After 1 h at -75 °C, deuteriolysis with D2O
(0.2 mL) afforded 0.15 g (90%, 100% d) of 11a (eluent: CH2-
Cl2/hexane 50:50). The 1H and 13C NMR data of this product
showed the replacements of 3′-H by 3′-D and 3′-CH by 3′-CD,
respectively.
2-(4-F lu or o-3-iod op h en yl)p yr id in e (11b). A solution of
the fluoride 10 (0.17 g, 1.0 mmol) and potassium tert-butoxide
(0.11 g, 1.0 mmol) in THF (3 mL) was successively treated with
BuLi (1.0 mmol) at -75 °C and, 1 h later, a solution of iodine
(0.25 g, 1.0 mmol) in THF (3 mL) to afford 0.19 g (64%) of 11b
(eluent: petrol/CH2Cl2 80:20): pale yellow oil; 1H NMR (CDCl3)
δ 7.14 (t, 1H, J ) 8.1 Hz), 7.25 (ddd, 1H, J ) 7.9, 4.8, 1.0 Hz),
7.66 (d, 2H, J ) 8.0 Hz), 7.75 (td, 1H, J ) 7.9, 1.7 Hz), 7.93
(ddd, 1H, J ) 8.5, 4.8, 2.2 Hz), 8.41 (dd, 1H, J ) 6.1, 2.2 Hz),
8.67 (d, 1H, J ) 4.6 Hz); 13C NMR (CDCl3) δ 81.7 (d, J ) 25
Hz), 115.6 (d, J ) 24 Hz), 120.2, 122.4, 122.3, 128.5 (d, J )
7.2 Hz), 136.9, 137.9, 149.7, 157.2 (d, J ) 249 Hz), 164.6; IR
(KBr) ν 3064, 3006, 1590, 1563, 1494, 1462, 1433, 1261, 778.
Anal. Calcd for C11H7FIN (299.09): C, 44.18; H, 2.36; N, 4.68.
Found: C, 44.28; H, 2.07; N, 4.98.
8.2 Hz), 8.06 (d, 1H, J ) 8.5 Hz), 8.60 (d, 1H, J ) 5.6 Hz); 13
C
NMR (CDCl3) δ 104.0 (t, J ) 25 Hz), 113.1 (d, J ) 26 Hz),
120.8, 126.3, 126.7, 127.2, 127.7, 130.3, 136.9, 142.1, 142.7 (t,
J ) 10 Hz), 158.0, 162.8 (dd, J ) 249, 13 Hz); IR (KBr) ν 3096,
3060, 1626, 1599, 1583, 1431, 1392, 1356, 1118, 985, 822, 694.
Anal. Calcd for C15H9F2N (241.24): C, 74.68; H, 3.76; N, 5.81.
Found: C, 74.52; H, 3.86; N, 5.82.
2-(2-[2H]-3-flu or op h en yl)p yr id in e (7a ). A solution of the
fluoride 1 (0.17 g, 1.0 mmol) in THF (3 mL) was successively
treated with BuLi (1.0 mmol) at -75 °C and, 1 h later, D2O
(28) Coulson, D. R. Inorg. Synth. 1972, 13, 121.
(29) Beadle, J . R.; Korzeniowski, S. H.; Rosenberg, D. E.; Garcia-
Slanga, B. J .; Gokel, G. W. J . Org. Chem. 1984, 49, 1594-1603.
(30) Ohkura, K.; Seki, K.; Terashima, M.; Kanaoka, Y. Tetrahedron
Lett. 1989, 30, 3433-3436.
(31) Gosmini, C.; Lasry, S.; Nedelec, J . Y.; Perichon, J . Tetrahedron
1998, 54, 1289-1298.
(32) van der Sluis, M.; Beverwijk, V.; Termaten, A.; Bickelhaupt,
F.; Kooijman, H.; Spek, A. L. Organometallics 1999, 18, 1402-1407.
2-(4-F lu or o-3,5-d iiod op h en yl)p yr id in e (12). A solution
of the dihalide 11b (0.30 g, 1.0 mmol) in THF (2 mL) was added
6770 J . Org. Chem., Vol. 69, No. 20, 2004

Deprotonation of 2-(Halophenyl)pyridines and 1-(Halophenyl)isoquinolines
to a solution of LTMP [obtained by adding BuLi (1.0 mmol) to
a solution of 2,2,6,6-tetramethylpiperidine (0.19 mL, 1.1 mmol)
in THF (2 mL) at 0 °C] at -75 °C. After 1 h at -75 °C,
quenching with a solution of iodine (0.25 g, 1.0 mmol) in THF
(3 mL) afforded 0.28 g (65%) of 12 (eluent: CH2Cl2): white
powder; mp 160-161 °C; 1H NMR (CDCl3) δ 7.28 (ddd, 1H, J
) 7.4, 4.8, 1.0 Hz), 7.66 (d, 1H, J ) 7.9 Hz), 7.78 (td, 1H, J )
8.0, 1.7 Hz), 8.37 (d, 2H, J ) 5.4 Hz), 8.68 (d, 1H, J ) 4.9 Hz);
13C NMR (CDCl3) δ 80.7 (d, J ) 29 Hz), 120.4, 122.9, 137.1,
138.0, 138.7, 149.9, 153.4, 160.7 (d, J ) 245 Hz); IR (KBr) ν
3086, 3005, 1584, 1449, 1429, 1287, 1246, 1154, 780, 739, 602.
Anal. Calcd for C11H6FI2N (424.98): C, 31.09; H, 1.42; N, 3.30.
Found: C, 31.33; H, 1.02; N, 3.27.
later, D2O (0.1 mL) to afford 0.22 g (91%, 72% d) of 16a
(eluent: petrol/AcOEt 80:20). The 1H and 13C NMR data of
this product showed the replacements of 2′-H by 2′-D, and 2′-
CH by 2′-CD, respectively.
1-(3-Ch lor o-2-iod op h en yl)isoqu in olin e (16b). A solution
of the chloride 5 (0.24 g, 1.0 mmol) in THF (3 mL) was
successively treated with BuLi (1.0 mmol) at -75 °C and, 1 h
later, a solution of iodine (0.25 g, 1.0 mmol) in THF (3 mL) to
afford 0.24 g (67%) of 16b (eluent: CH2Cl2/AcOEt 95:5): pale
1
yellow oil; H NMR (CDCl3) δ 7.27 (dd, 1H, J ) 7.5, 1.5 Hz),
7.44 (t, 1H, J ) 7.7 Hz), 7.6 (m, 3H), 7.7 (m, 2H), 7.92 (d, 1H,
J ) 8.3 Hz), 8.63 (d, 1H, J ) 5.7 Hz); 13C NMR (CDCl3) δ 102.4,
120.8, 126.4, 126.9, 126.9, 127.5, 127.8, 128.9, 129.1, 130.3,
136.4, 139.5, 141.9, 147.0, 162.3; IR (KBr) ν 3052, 1621, 1583,
1557, 1396, 1386, 1356, 827, 787, 752. Anal. Calcd for C15H9-
ClIN (365.60): C, 49.28; H, 2.48; N, 3.83. Found: C, 49.26; H,
2.57; N, 3.78.
2-(2-[2H]-3-flu or o-4-iod op h en yl)p yr id in e (13). A solu-
tion of the dihalide 7b (0.30 g, 1.0 mmol) in THF (2 mL) was
treated with a solution of LTMP [obtained by adding BuLi (1.0
mmol) to a solution of 2,2,6,6-tetramethylpiperidine (0.19 mL,
1.1 mmol) in THF (2 mL) at 0 °C] at -75 °C. After 1 h at -75
°C, deuteriolysis with D2O (0.1 mL) afforded 0.21 g (69%, 72%
d) of 13 (eluent: CH2Cl2/AcOEt 95:5): pale yellow powder; mp
1-(3,5-Diflu or o-4-iod op h en yl)isoqu in olin e (17a ). A solu-
tion of the difluoride 6 (0.24 g, 1.0 mmol) in THF (3 mL) was
successively treated with BuLi (1.0 mmol) at -75 °C and, 1 h
later, a solution of iodine (0.25 g, 1.0 mmol) in THF (3 mL) to
afford 0.27 g (73%) of 17a (eluent: CH2Cl2/AcOEt 98:2): mp
1
67-68 °C; H NMR (CDCl3) δ 7.28 (ddd, 1H, J ) 7.9, 4.8, 1.3
Hz), 7.54 (d, 1H, J ) 8.3 Hz), 7.70 (d, 1H, J ) 7.9 Hz), 7.77
(td, 1H, J ) 8.0, 1.8 Hz), 7.83 (dd, 1H, J ) 8.2, 1.8 Hz), 8.68
(d, 1H, J ) 4.5 Hz); 13C NMR (CDCl3) δ 81.2 (d, J ) 26 Hz),
113.2 (m), 119.7, 122.5, 123.3 (d, J ) 2.6 Hz), 136.4, 139.0,
141.4 (d, J ) 6.9 Hz), 149.3, 154.3, 161.7 (d, J ) 245 Hz); IR
(KBr) ν 3006, 1589, 1548, 1456, 1434, 1383, 1221, 993, 776,
757, 741, 722. Anal. Calcd for C11H6FIND (300.09): C, 44.03;
“H”,33 2.39; N, 4.67. Found: C, 44.18; “H”, 2.45; N, 4.42.
2-(2-[2H]-3-ch lor o-4-iod op h en yl)p yr id in e (14). A solu-
tion of the dihalide 8b (0.32 g, 1.0 mmol) in THF (2 mL) was
treated with a solution of LTMP [obtained by adding BuLi (1.0
mmol) to a solution of 2,2,6,6-tetramethylpiperidine (0.19 mL,
1.1 mmol) in THF (2 mL) at 0 °C] at -75 °C. After 1 h at -75
°C, deuteriolysis with D2O (0.1 mL) afforded 0.10 g (30%, 80%
d) of 14 (eluent: CH2Cl2): colorless oil; 1H NMR (CDCl3) δ
7.28 (ddd, 1H, J ) 7.2, 4.8, 1.2 Hz), 7.57 (d, 1H, J ) 8.3 Hz),
7.69 (d, 1H, J ) 8.0 Hz), 7.77 (td, 1H, J ) 7.7, 1.8 Hz), 7.94 (d,
1H, J ) 8.3 Hz), 8.69 (d, 1H, J ) 4.9 Hz); 13C NMR (CDCl3) δ
98.7, 120.2, 122.9, 126.0, 127.5, 136.8, 139.0, 140.3, 141.1,
149.6, 155.7; IR (KBr) ν 3055, 3004, 1507, 1471, 1452, 1427,
1353, 1000, 787, 778, 753, 692. Anal. Calcd for C11H6ClIND
(316.55): C, 41.74; “H”,33 2.26; N, 4.42. Found: C, 41.68; “H”,
2.37; N, 4.48.
1
164 °C; H NMR (CDCl3) δ 7.27 (d, 2H, J ) 6.9 Hz), 7.60 (t,
1H, J ) 7.7 Hz), 7.72 (m, 2H), 7.92 (d, 1H, J ) 8.2 Hz), 8.06
(d, 1H, J ) 8.5 Hz), 8.60 (d, 1H, J ) 5.7 Hz); 13C NMR (CDCl3)
δ 71.4 (t, J ) 29 Hz), 112.9 (d, J ) 26 Hz), 120.9, 126.3, 126.4,
127.2, 127.8, 130.3, 136.3, 142.1, 142.6 (t, J ) 8.9 Hz), 157.0,
162.4 (dd, J ) 248, 6.3 Hz); IR (KBr) ν 3064, 1551, 1409, 1389,
1360, 1019, 1012, 866, 856, 819, 752, 686, 658. Anal. Calcd
for C15H8F2IN (367.14): C, 49.07; H, 2.20; N, 3.82. Found: C,
49.17; H, 2.34; N, 3.56.
1-(3,5-Diflu or o-4-(t r im et h ylsilyl)p h en yl)isoq u in olin e
(17b). A solution of the difluoride 6 (0.24 g, 1.0 mmol) in THF
(3 mL) was successively treated with BuLi (1.0 mmol) at -75
°C and, 1 h later, chlorotrimethylsilane (0.13 mL, 1.0 mmol)
to afford 0.23 g (72%) of 17b (eluent: cyclohexane/AcOEt 90:
1
10): pale yellow oil; H NMR (CDCl3) δ 0.66 (s, 9H), 7.38 (d,
2H, J ) 7.5 Hz), 7.75 (t, 1H, J ) 7.7 Hz), 7.85 (m, 2H), 8.06
(d, 1H, J ) 8.3 Hz), 8.31 (d, 1H, J ) 8.7 Hz), 8.79 (d, 1H, J )
5.7 Hz); 13C NMR (CDCl3) δ 112.5 (d, J ) 31 Hz), 113.8 (t, J
) 35 Hz), 120.5, 126.1, 126.6, 127.0, 127.5, 130.2, 136.7, 141.9,
143.4 (t, J ) 10 Hz), 157.9, 166.7 (dd, J ) 245, 17 Hz); IR
(KBr) ν 3054, 2958, 2901, 1621, 1538, 1398, 1252, 1186, 1001,
906, 847, 827, 659. Anal. Calcd for C18H17F2NSi (313.43): C,
68.98; H, 5.47; N, 4.47. Found: C, 69.03; H, 5.65; N, 4.42.
1-(2-[2H]-3-flu or op h en yl)isoqu in olin e (15a ). A solution
of the fluoride 4 (0.22 g, 1.0 mmol) in THF (3 mL) was
successively treated with BuLi (1.0 mmol) at -75 °C and, 1 h
later, D2O (0.1 mL) to afford 0.21 g (94%, 91% d) of 15a
(eluent: petrol/AcOEt 80:20). The 1H and 13C NMR data of
this product showed the replacements of 2′-H by 2′-D, and 2′-
CH by 2′-CD, respectively.
1-(3-F lu or o-2-iod op h en yl)isoqu in olin e (15b). A solution
of the fluoride 4 (0.22 g, 1.0 mmol) in THF (3 mL) was
successively treated with BuLi (1.0 mmol) at -75 °C and, 1 h
later, a solution of iodine (0.25 g, 1.0 mmol) in THF (3 mL) to
afford 0.21 g (70%) of 15b (eluent: CH2Cl2/AcOEt 95:5): pale
yellow oil; 1H NMR (CDCl3) δ 7.2 (m, 2H), 7.5 (m, 3H), 7.8 (m,
2H), 7.93 (d, 1H, J ) 8.3 Hz), 8.63 (d, 1H, J ) 5.7 Hz); 13C
NMR (CDCl3) δ 85.8 (d, J ) 26 Hz), 114.9 (d, J ) 24 Hz), 120.6,
125.7 (d, J ) 3.0 Hz), 126.7, 126.8, 127.1, 127.3, 129.6 (d, J )
8.4 Hz), 130.2, 136.1, 141.7, 146.1, 160.8, 161.5 (d, J ) 246
Hz); IR (KBr) ν 3054, 1583, 1558, 1424, 1386, 1359, 1241, 902,
828, 818, 798, 786, 750. Anal. Calcd for C15H9FIN (349.15):
C, 51.60; H, 2.60; N, 4.01. Found: C, 51.48; H, 2.47; N, 4.02.
1-(2-[2H]-3-Ch lor op h en yl)isoqu in olin e (16a ). A solution
of the chloride 5 (0.24 g, 1.0 mmol) in THF (3 mL) was
successively treated with BuLi (1.0 mmol) at -75 °C and, 1 h
1-(2-[2H]-3-F lu or o-4-iod op h en yl)isoqu in olin e (18). A
solution of the dihalide 15b (0.35 g, 1.0 mmol) in THF (2 mL)
was treated with a solution of LTMP [obtained by adding BuLi
(1.0 mmol) to a solution of 2,2,6,6-tetramethylpiperidine (0.19
mL, 1.1 mmol) in THF (2 mL) at 0 °C] at -75 °C. After 1 h at
-75 °C, deuteriolysis with D2O (0.1 mL) afforded 0.26 g (74%,
74% d) of 18 (eluent: CH2Cl2/AcOEt 95:5): pale yellow powder;
1
mp 125 °C; H NMR (CDCl3) δ 7.27 (d, 1H, J ) 7.6 Hz), 7.58
(td, 1H, J ) 7.6, 1.0 Hz), 7.69 (d, 1H, J ) 5.7 Hz), 7.72 (td,
1H, J ) 7.0, 0.9 Hz), 7.91 (d, 1H, J ) 8.0 Hz), 7.93 (d, 1H, J
) 8.0 Hz), 8.06 (d, 1H, J ) 8.5 Hz), 8.60 (d, 1H, J ) 5.7 Hz);
13C NMR (CDCl3) δ 81.6 (d, J ) 25 Hz), 116.9 (d, J ) 25 Hz),
120.3, 125.9, 126.4, 126.9, 127.0 (d, J ) 3.2 Hz), 127.4, 130.0,
136.5, 138.9 (d, J ) 1.4 Hz), 141.6 (d, J ) 6.7 Hz), 141.9, 157.8,
161.3 (d, J ) 246 Hz); IR (KBr) ν 3046, 1405, 1392, 1352, 1224,
870, 837, 828, 808, 746, 678. Anal. Calcd for C15H8FIND
(350.15): C, 51.45; “H”,33 2.62; N, 4.00. Found: C, 51.58; “H”,
2.77; N, 4.08.
(33) The fictitious hydrogen percentage (“H”) was calculated as 1.008
(h + 20.027/18.015 × d)/molecular weight, where h and d stand for
the number of hydrogen and, respectively, deuterium atoms in the cross
formula: Schlosser, M.; Choi, J . H.; Takagishi, S. Tetrahedron 1990,
46, 5633-5648.
J O049454V
J . Org. Chem, Vol. 69, No. 20, 2004 6771