New syntheses of substituted pyridines via bromine-magnesium exchange

Article abstract of DOI:10.1016/S0040-4020(00)00027-2

Bromine-magnesium exchange using iPrMgCl in THF at room temperature on 2-, 3- and 4-bromopyridines allowed the synthesis of various functionalized pyridines. The methodology was successfully used for the synthesis of 4- azaxanthone. Moreover, single exchange reactions observed on 2,6-, 3,5-, 2,3- and 2,5-dibromopyridines, with complete regioselectivity in the case of 2,3- and 2,5-dibromopyridines, afforded substituted bromopyridines, which were then involved in a second exchange step to provide difunctionalized pyridines. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00027-2

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 1349–1360
New Syntheses of Substituted Pyridines via
Bromine–Magnesium Exchange
´
´
Franc¸ois Trecourt, Gilles Breton, Veronique Bonnet, Florence Mongin, Francis Marsais and
*
´
Guy Queguiner
´ ´
Laboratoire de Chimie Organique Fine et Heterocyclique, IRCOF, Place E. Blondel, BP 08, 76131 Mont-Saint-Aignan, France
Received 7 September 1999; accepted 6 January 2000
Abstract—Bromine–magnesium exchange using iPrMgCl in THF at room temperature on 2-, 3- and 4-bromopyridines allowed the
synthesis of various functionalized pyridines. The methodology was successfully used for the synthesis of 4-azaxanthone. Moreover, single
exchange reactions observed on 2,6-, 3,5-, 2,3- and 2,5-dibromopyridines, with complete regioselectivity in the case of 2,3- and 2,5-
dibromopyridines, afforded substituted bromopyridines, which were then involved in a second exchange step to provide difunctionalized
pyridines. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Introduction
A survey of the literature revealed that significant results
were reported from iodopyridines,4 which, however, are
expensive and rarely commercially available. In those
cases, iodine–magnesium exchange was observed when
the iodides were treated with alkyl or phenylmagnesium
halides. Paradies5 described chlorine–magnesium exchange
by reaction of chloropyridines with phenylmagnesium
halides, but the results could not be repeated. As far as
bromopyridines are concerned, bromine exchange was
reported by Paradies5 using phenylmagnesium halides, and
Meunier6 using isopropylmagnesium chloride in THF at
Ϫ25ЊC. The resulting Grignard derivatives were trapped
with electrophiles, but no yields were mentioned.5
Interest in pyridine natural products and pharmaceuticals, as
well as pyridine building blocks for various applications
such as material science and supramolecular chemistry,
has resulted in extensive efforts on synthesis methodologies.
Lithiation reactions allow many functionalizations1 either
by direct reaction with electrophiles or transmetalation to
allow cross-coupling reactions.
Nevertheless, lithiation often requires low temperature,
which can be difficult to realize on an industrial scale. More-
over, halogen–lithium exchange is very sensitive to reaction
temperature, particularly for bromopyridines.1a,2 In this
case, the reaction has to be performed at Ϫ100ЊC in tetra-
hydrofuran (THF) or around Ϫ40ЊC in diethyl ether, in
order to avoid side-reactions such as deprotonation, addition
to the substrate, elimination of lithium bromide (to give
pyridynes), bromine migration (‘halogen dance’) or even
ring opening reactions.
We recently reported7 a convenient access to pyridyl-
magnesium chlorides, starting from commercially available
bromopyridines. Herein, details of our investigations on the
elaboration of mono and difunctionalized pyridines from the
corresponding bromo and dibromopyridines are recorded.8
So, we have been interested in the development of pyridyl-
magnesium reagents that could be involved in either
electrophilic trapping or coupling reactions.
Results and Discussion
Various alkylmagnesium halides, reaction times, and
solvents were tested in order to optimize the exchange
conditions on bromopyridines and the trapping of the
pyridine Grignard reagents with electrophiles. It was
found that iPrMgCl was the best exchange reagent;
tBuMgCl among different bulky reagents did not give
satisfying results. The reaction was performed in various
solvents such as diethyl ether, dioxanes, tetrahydropyran,
hexamethylenephosphoramide, THF, or even mixtures of
these solvents. THF proved to be the best solvent for the
exchange reaction. It was demonstrated by gas chromatography
Halogen–magnesium exchange reactions were preferred for
generating pyridylmagnesium halides since the direct access
to pyridine Grignard reagents by the oxidative addition of
magnesium to the halopyridine is difficult to achieve, even
with magnesium activation.3
Keywords: pyridine; Grignard reagents; exchange reactions; regioselection.
* Corresponding author. Fax: ϩ33-(0)2-35-52-29-62;
e-mail: guy.queguiner@insa-rouen.fr
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00027-2

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F. Trecourt et al. / Tetrahedron 56 (2000) 1349–1360
1350
that, under these conditions, the halogen that was attached to
the pyridine Grignard reagent was chlorine, as isopropyl
bromide was selectively formed.
Under the same exchange reaction conditions, 3-bromo-
pyridine (3) readily reacts with iPrMgCl, and the resulting
pyridylmagnesium chloride was trapped with various
electrophiles in moderate to high yields. In the case of
acetaldehyde (entry 6), an excess of electrophile was
successfully used at a lower temperature. It was noted that
in the case of benzoyl chloride, the tertiary alcohol resulting
from the reaction of 3-pyridylmagnesium chloride with
ketone 4i was never observed and did not explain the low
yield. It was shown that 3-pyridylmagnesium chloride is not
a suitable reagent for alkylation (entry 11), but that it allows
a simple access to bis(3-pyridyl)mercury (4m) (entry 14)
(Scheme 2, Table 2). In summary, 2- and 3-pyridylmagne-
sium chlorides could be easily prepared, but the former were
less reactive towards electrophiles.
As far as trapping with electrophiles is concerned, several
amine complexing agents of magnesium were tested in
order to increase the reactivity of the pyridylmagnesium
chloride. It was observed that the addition of the complex-
ing agent enhanced not only the nucleophilicity but also the
basicity of the Grignard reagent. As a result, the effect
largely depends on the nature of the electrophile. Thus,
addition of triethylamine (1 equiv.) to the reaction mixture
before introduction of the electrophile, improved the yields
in some cases.
2-Bromopyridine (1) reacts with iPrMgCl in THF at room
temperature. The 2-pyridylmagnesium chloride thus
obtained was treated with various electrophiles at room
temperature. Deuteriolysis afforded almost quantitatively
completely 2-deuterated pyridine, accompanied by less
than 10% of 2-bromopyridine (1). Reaction with benzalde-
hyde (entry 1) provided the corresponding alcohol in high
yield (80%), the remaining 20% being essentially pyridine
(less than 5% of starting compound 1 is recovered), as
shown by GC assays. The 2-bromopropane formed during
the exchange seems to have no effect on the reactions. In the
case of enolizable carbonyl compounds (entries 2–7),
moderate to good yields of alcohols were obtained. Acid
chlorides (entries 8 and 9) gave low yields of the corre-
sponding ketones, and mixtures of degradation compounds
were formed. Disulfides (entries 10 and 11) produced the
expected sulfides in moderate yields. Iodine (entry 12)
allowed the synthesis of 2-iodopyridine (2l) in an excellent
yield (Scheme 1, Table 1).
Due to its instability, 4-bromopyridine (5b) has to be used in
the magnesium-exchange reaction immediately after
neutralization of the corresponding commercial hydro-
chloride (5a). Bromine–magnesium exchange was also
Scheme 2.
Table 2. 3-Pyridylmagnesium chloride: trapping with various electrophiles
Entry Electrophile
E
Product Yield (%)a
1
PhCHO
CH(OH)Ph
4a
84, 93b
2
4b
74
3
4
4c
32, 40b
Scheme 1.
Table 1. 2-Pyridylmagnesium chloride: trapping with various electrophiles
4d
46
Entry Electrophile
E
Product Yield (%)a
1
2
3
4
5
PhCHO
CH3CHO
CH3CH2CHO
CH3(CH2)4CHO
PhCH2CHO
CH(OH)Ph
CH(OH)CH3
CH(OH)CH2CH3
CH(OH)(CH2)4CH3 2d
CH(OH)CH2Ph
2a
2b
2c
80
79
54
42
42
5
6
7
8
tBuCHO
CH3CHO
PhCOPh
EtCOEt
PhCOCl
iPrCOCl
CH3I or CH3CH2I CH3 or CH2CH3
CH3SSCH3
I2
CH(OH)tBu
CH(OH)CH3
C(OH)Ph2
C(OH)Et2
COPh
4e
4f
4g
4h
4i
78
51, 14b, 74c
51
58, 16b
35d
2e
9
10
11
12
13
COiPr
4j
12d
0
SCH3
I
4k
4l
49, 58b
78
6
2f
25
7
8
9
10
11
12
CH3COCH3
PhCOCl
CH3COCl
PhSSPh
CH3SSCH3
I2
C(OH)(CH3)2
COPh
COCH3
SPh
SCH3
I
2g
2h
2i
2j
2k
2l
30
e
11b
15
14
HgBr2
4m
80
45b
40b
97
a Isolated yields based on 3.
b 1 equiv. of triethylamine was added before quenching with the electro-
phile.
a Isolated yields based on 1.
c 10 equiv. of CH3CHO were used at Ϫ20ЊC.
d Addition of RCOCl at Ϫ70ЊC and gentle warming to rt.
e 0.5 equiv. was used.
b 1 equiv. of triethylamine was added before quenching with the electro-
phile.

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F. Trecourt et al. / Tetrahedron 56 (2000) 1349–1360
1351
Scheme 5.
Scheme 3.
Table 5. 2-(6-d)Pyridylmagnesium chloride: trapping with electrophiles
Table 3. 4-Pyridylmagnesium chloride: trapping with various electrophiles
Product
E0
Yield (%)a
Entry Electrophile
E
Product Yield (%)a
9a
9b
CH(OH)Ph
I
66
42
1
2
PhCHO
CH(OH)Ph
6a
6b
64
40
a Isolated yields based on 8a.
The second bromine–magnesium exchange could be
performed on the bromo derivative 8a; subsequent reaction
with an electrophile provided the expected 2,6-disubstituted
pyridines 9a–b (Scheme 5, Table 5).
3
4
5
6
7
CH3(CH2)4CHO
(CH3)2CHCHO
PhCOPh
PhSSPh
I2
CH(OH)(CH2)4CH3 6c
CH(OH)CH(CH3)2 6d
42
39
29
45b
51
C(OH)Ph2
SPh
I
6e
6f
A single exchange was also established from 3,5-dibromo-
pyridine (10), and afforded 3-bromo-5-substituted pyridines
11a–b in good yields. Consecutive exchange of the second
bromine atom in a one-pot procedure could be carried out to
give 3,5-disubstituted pyridines 12a–b. So, two different
substituents can be introduced at C3 and C5, using this
one-pot methodology.
6g
a Isolated yields based on hydrochloride 5a.
b 1 equiv. of triethylamine was added before quenching with the electro-
phile.
observed, and trapping reactions could be achieved in
moderate to good yields (Scheme 3, Table 3).
This study was then extended to dibromopyridines with the
purpose of studying the regioselectivity of the exchange.
2,6-Dibromopyridine (7) reacts almost quantitatively with
iPrMgCl in a single exchange reaction (even with an excess
of reagent), as demonstrated by deuteriolysis (entry 1). The
yields largely depend on the trapping step with the electro-
philes (Scheme 4, Table 4).
Scheme 6.
Scheme 4.
Table 6. 5-Bromo-3-pyridylmagnesium chloride and one pot 3- and 5-
pyridylmagnesium chlorides: trapping with electrophiles
Table 4. 6-Bromo-2-pyridylmagnesium chloride: trapping with various
E0
Yield%a
electrophiles
Product
R
E
Entry
Electrophile
E
Product
Yield (%)a
5-Bromo-3-pyridylmagnesium chloride
11a
11b
14
H
H
Cl
D
82b
76
99
1
2
3
4
5
D2O
D
8a
8b
8c
8d
8e
95b,c
42c
74c
45c
90d
CH(OH)Ph
H
PhCHO
ClSi(CH3)3
CH3SSCH3
I2
CH(OH)Ph
Si(CH3)3
SCH3
One pot 3- and 5-pyridylmagnesium chlorides
I
12a
12b
15f
H
H
Cl
CH(OH)Ph
Si(CH3)3
CH(OH)Ph
CH(OH)Ph
CH)(OH)Ph
CH(OH)Ph
49
52
74
a Isolated yields based on 7.
b 100% of deuterium incorporation was observed from the 1H NMR
spectra integration values.
a Isolated yields based on 10 or 13.
c 2 equiv. of iPrMgCl and electrophile were used.
d 4 equiv. of iPrMgCl and I2 were used.
b 100% of deuterium incorporation was observed from the 1H NMR
spectra integration values.

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F. Trecourt et al. / Tetrahedron 56 (2000) 1349–1360
1352
hydrolysis of the reaction mixture. The one-pot procedure
applied to dibromo compound 13 led to difunctionalized
pyridine 15 in 74% yield (the same procedure applied to
dibromo derivative 10 only proceeds in 49% yield). The
chlorine atom at C4 seems to enhance the rate of
the bromine–magnesium exchange and/or the reactivity of
the Grignard intermediate (Scheme 6, Table 6).
Scheme 7.
Reacting 2,3-dibromopyridine8 (16) with iPrMgCl at room
temperature, followed by quenching with benzaldehyde or
iodine, afforded 2-bromo-3-substituted pyridines 17a–b in
high yields (Scheme 7, Table 7). The observed selectivity of
the exchange could be related to the strength of the carbon–
bromine bond; conjugation of the bromine at C2 with CyN
bond could justify the regioselective reaction at C3.
Table 7. 2-Bromo-3-pyridylmagnesium chloride: trapping with electro-
philes
Product
E
Yield (%)a
17a
17b
CH(OH)Ph
I
92
80
a Isolated yields based on 16.
2-Bromo-5-substituted pyridines, (19a–c), were synthe-
sized from 2,5-dibromopyridine (18), following the same
procedure as for the 2,3 isomer. The same selectivity was
observed (Scheme 8, Table 8). Thus, from dibromopyri-
dines 16 and 18, bromine–magnesium exchange first
occurred at C3 or C5, as previously reported2d,f when
these compounds were treated with butyllithium in THF at
Ϫ100ЊC.
Scheme 8.
3,4-Dibromopyridine (20) reacts under the same conditions
to give exchange at C3 and C4 in a respectively 65:35 ratio
(Scheme 9).
Table 8. 2-Bromo-5-pyridylmagnesium chloride: trapping with electro-
philes
Product
E
Yield (%)a
This lack of regioselectivity has already been reported in the
case of bromine–lithium exchange.2f
19a
19b
19c
D
64b
86
82
CH(OH)Ph
I
Bromine–magnesium exchange has been successfully used
for the synthesis in the azaxanthone series.9 3-Bromo-2-
chloropyridine (23) reacted under the conditions previously
described to give the desired alcohol 24 in good yield.
Compound 24 can easily be converted to 4-azaxanthone
via oxidation and cyclization steps.10 The overall yield of
the synthesis is 55% (Scheme 10).
a Isolated yields based on 16.
b 100% of deuterium incorporation was observed from the 1H NMR
spectra integration values.
In order to study the effect of an additional halogen substi-
tuent, 4-chloro-3,5-dibromopyridine (13) was treated under
the same conditions. A single exchange reaction at C3
gave, quantitatively, 3-bromo-4-chloropyridine (14) after
In conclusion, 2-, 3- and 4-substituted pyridines could be
Scheme 9.
Scheme 10.

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F. Trecourt et al. / Tetrahedron 56 (2000) 1349–1360
1353
prepared from the corresponding bromo derivatives by
bromine–magnesium exchange reaction. The main advan-
tage of this methodology is the relative stability of these
organometallic species: bromine–lithium exchange has to
be performed at low temperature to prevent side reactions
whereas bromine–magnesium exchange proceeds well at
room temperature. Under these conditions, the overall
reaction proved to be highly chemoselective and no side
products were detected. Regioselectivity of the reaction on
dibromopyridines, as well as yields obtained after trapping
with electrophiles, are analogous to that observed during
bromine–lithium exchange reaction.2 Subsequent coupling
reactions at C2 on bromo substituted pyridines thus obtained
could allow the synthesis of more diversified substituted
pyridines.
acetaldehyde as an electrophile gave 79% (CH2Cl2/Et21O,
90:10) of 2b: mp 38–40ЊC (Lit. 12b mp 39–40ЊC); H
NMR (CDCl3) d 1.42 (d, 3H, CH3), 4.80 (q, 1H, CHOH),
5.97 (s, 1H, OH), 7.00 (m, 1H, H5), 7.29 (d, 1H, H3), 7.62 (m,
1H, H4), 8.30 (dd, 1H, H6), J4,6ˆ2.0, J5,6ˆ5.0, JCH3–CHˆ6.6,
J3,4ˆ8.1 Hz (the 1H NMR data are in accordance with those
of the literature);12 13C NMR (CDCl3) d 22.6 (CH3), 68.2
(CHOH), 118.4 (C3), 120.8 (C5), 135.9 (C4), 146.2 (C6),
163.2 (C2); IR (KBr) n 3367, 2974, 2929, 1712, 1596,
1435, 1120, 1084, 787 cmϪ1. Anal. Calcd for C7H9NO
(123.16): C, 68.27; H, 7.37; N, 11.37. Found: C, 68.51; H,
7.45; N, 11.07%.
a-Ethyl-2-pyridinemethanol (2c). Procedure A, using
propanal as an electrophile gave 54% (CH2Cl2/Et2O,
1
90:10) of 2c: oil; H NMR (CDCl3) d 0.99 (t, 3H, CH3),
1.90 (q, 2H, CH2), 4.82 (t, 1H, CHOH), 5.30 (s, 1H, OH),
6.97 (m, 1H, H5), 7.31 (d, 1H, H3), 7.64 (m, 1H, H4), 8.50 (d,
1H, H6), J5,6ˆ4.1, JCH3–CH2ˆ6.8, J3,4ˆ8.0 Hz; 13C NMR
(CDCl3) d 9.9 (CH3), 31.4 (CH2), 74.7 (CHOH), 120.8
(C3), 122.5 (C5), 137.1 (C4), 148.3 (C6), 163.2 (C2) (the
NMR data are in accordance with those of the literature);12d
IR (neat) n 3387, 3242, 2967, 2934, 2897, 2243, 2101, 1597,
1436, 1049, 732, 565 cmϪ1. Anal. Calcd for C8H11NO
(137.18): C, 70.04; H, 8.08; N, 10.21. Found: C, 69.78; H,
8.27; N, 10.14%.
Experimental
Melting points were measured on a Kofler apparatus. The
NMR spectra were recorded in CDCl3 or DMSO-d6 with a
Bruker AM 200 spectrometer (1H at 200 MHz and 13C at
50 MHz). IR spectra were taken on a Perkin Elmer FT IR
205 spectrometer, and main IR absorptions are given in
cmϪ1. Elemental analyses were performed on a Carlo Erba
1106 apparatus.
Starting materials
a-Pentyl-2-pyridinemethanol (2d). Procedure A, using
hexanal as an electrophile gave 42% (Et2O) of 2d: oil; H
1
THF was distilled from benzophenone/Na. Reactions
were carried out under dry Ar. Silica gel (Geduran Si 60,
0.063–0.200 mm) was purchased from Merck. iPrMgCl
(2 M) in THF was purchased from Aldrich. 2- and 3-Bromo-
pyridines were supplied by Acros; 4-bromopyridine hydro-
chloride, 2,5-, 2,6- and 3,5-dibromopyridines by Lancaster.
3-Bromo-2-chloropyridine,11a 4-chloro-3,5-dibromopyri-
dine,11b 2,3-dibromopyridine8 and 3,4-dibromopyridine11c
were prepared according to literature procedures.
Procedures were generally performed on a 10 mmol scale.
NMR (CDCl3) d 0.81 (t, CH3, 3H), 1.5 (m, 8H, CH2), 4.20
(s, 1H, OH), 4.60 (t, 1H, CHOH), 7.15 (dd, 1H, H5), 7.27
(dd, 1H, H3), 7.63 (m, 1H, H4), 8.42 (dd, 1H, H6), J4,6ˆ1.9,
J5,6ˆ5.0, JCH3–CH2ˆ6.3, JCH–CH2ˆ6.4, J3,4ˆ7.8, J4,5ˆ8.0 Hz
literature);12e 13C NMR (CDCl3) d 14.5 (CH3), 22.9 (CH2),
25.3 (CH2), 32.2 (CH2), 38.9 (CH2), 73.2 (CHOH), 120.7
(C3), 122.6 (C5), 137.0 (C4), 148.5 (C6), 162.8 (C2); IR
(neat) n 3390, 2930, 1731, 1572, 1470, 1434, 1049,
750 cmϪ1. Anal. Calcd for C11H17NO (179.26): C, 73.70;
H, 9.56; N, 7.81. Found: C, 73.76; H, 9.88; N, 7.54%.
1
(the H NMR data are in accordance with those of the
2-Substituted pyridines 2a–l: general procedure A
a-Benzyl-2-pyridinemethanol (2e). Procedure A, using
phenylacetaldehyde as an electrophile gave 42% (CH2Cl2/
Et2O, 90:10) of 2e: mp 116–118ЊC (Lit. 12f mp 117–
119ЊC); H NMR (CDCl3) d 3.13 (d, 2H, CH2), 3.90 (s,
1H, OH), 4.99 (t, 1H, CHOH), 7.3 (m, 8H, H3,4,5, Ph),
iPrMgCl (10 mmol) was added to 1 (0.95 mL, 1.6 g,
10 mmol) in THF (10 mL) at rt. After 2 h, the electrophile
(10 mmol) was added. After 18 h at rt, water (50 mL) was
added. Extraction with CH2Cl2 (3×20 mL), drying over
MgSO4 and column chromatography on silica gel (eluent)
afforded 2a–l.
1
8.62 (dd, 1H, H6), J4,6ˆ2.0, J5,6ˆ5.0, JCH2–CHˆ6.1 Hz
1
(the H NMR data are in accordance with those of the
literature);12f 13C NMR (CDCl3) d 45.6 (CH2), 74.4
0
(CHOH), 121.1 (C3), 122.8 (C5), 126.8 (C4 ), 128.7
a-Phenyl-2-pyridinemethanol (2a). Procedure A, using
0
0
0
0
0
(C2 ,6 ), 130.0 (C3 ,5 ), 136.8 (C4), 138.1 (C1 ), 148.8 (C6),
161.6 (C2); IR (KBr) n 3085, 3029, 2912, 1596, 1434,
1332, 1100, 1077, 1054, 1006, 774, 699 cmϪ1. Anal.
Calcd for C13H13NO (199.25): C, 78.36; H, 6.58; N, 7.03.
Found: C, 78.65; H, 6.77; N, 6.75%.
benzaldehyde as an electrophile gave 80% (CH2Cl2/Et2O,
1
90:10) of 2a: mp 72–73ЊC (lit.12 mp 72–74ЊC); H NMR
(CDCl3) d 3.79 (s, 1H, OH), 5.81 (s, 1H, CHOH), 7.3 (m,
8H, H3,4,5, Ph), 8.51 (dd, 1H, H6), J4,6ˆ2.0, J5,6ˆ4.7 Hz
1
(the H NMR data are in accordance with those of the
literature);12a 13C NMR (CDCl3) d 75.4 (CHOH), 121.7
0
0
0
0
0
a-Methylbis(2-pyridine)methanol (2f). Procedure A,
using 2-acetylpyridine as an electrophile gave 25%
(CH2Cl2/Et2O, 90: 10) of 2f: mp 46–48ЊC (Lit. 12g mp
(C3), 122.4 (C5), 127.4 (C2 ,6 ), 128.2 (C4 ), 128.9 (C3 ,5 ),
0
137.2 (C4), 140.1 (C1 ), 148.2 (C6), 158.2 (C2); IR (KBr) n
3340, 3112, 3094, 1594, 1494, 1435, 1050 cmϪ1. Anal.
Calcd for C12H11NO (185.23): C, 77.81; H, 5.99; N, 7.56.
Found: C, 77.98; H, 6.03; N, 7.68%.
1
47–49ЊC); H NMR (CDCl3) d 1.97 (s, 3H, CH3), 5.20 (s,
1H, OH), 7.1 (dd, 2H, 2H5), 7.7 (m, 4H, 2H4, 2H3), 8.46 (d,
2H, 2H6), J5,6ˆ4.8, J3,4ˆ4.2, J4,5ˆ7.1 Hz (the 1H NMR data
are in accordance with those of the literature);12h 13C NMR
a-Methyl-2-pyridinemethanol (2b). Procedure A, using

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F. Trecourt et al. / Tetrahedron 56 (2000) 1349–1360
1354
(CDCl3) d 29.1 (CH3), 75.9 (COH), 120.4 (2C3), 121.8
(2C5), 136.6 (2C4), 147.4 (2C6), 164.2 (2C2); IR (KBr) n
3380, 1595, 1575, 1150 cmϪ1. Anal. Calcd for C12H12N2O
(200.24): C, 71.98; H, 6.04; N, 13.99. Found: C, 71.70; H,
6.35; N, 13.71%.
those of the literature);12n IR (neat) n 2925, 1581, 1415,
1126, 757 cmϪ1. Anal. Calcd for C6H7NS (125.20): C,
57.56; H, 5.64; N, 11.19; S, 25.61. Found: C, 57.84; H,
5.49; N, 11.42; S, 25.33%.
2-Iodopyridine (2l). Procedure A, using iodine as an
electrophile (in this case, the reaction mixture was treated
with 50 mL of a 0.5 N aqueous sodium thiosulfate solution
instead of water) gave 97% (CH2Cl2/Et2O, 95: 5) of 2l: oil;
bp 92ЊC/15 mm Hg; 1H NMR (CDCl3) d 7.5 (m, 3H, H3,4,5),
8.3 (m, 1H, H6); 13C NMR (CDCl3) d 118.1 (C2), 122.7 (C5),
134.5 (C3), 137.3 (C4), 150.4 (C6) (the NMR data are in
accordance with those of the literature);12n IR (neat) n
1553, 1445, 1411, 755 cmϪ1. Anal. Calcd for C5H4IN
(205.00): C, 29.30; H, 1.97; N, 6.83. Found: C, 29.06; H,
1.76; N, 6.85%.
a,a-Dimethyl-2-pyridinemethanol (2g). Procedure A,
using acetone as an electrophile gave 30% (CH2Cl2/Et2O,
1
80:20) of 2g: mp 50ЊC (Lit. 12i mp 50–52ЊC); H NMR
(CDCl3) d 1.51 (s, 6H, CH3), 5.90 (s, 1H, OH), 7.7 (m,
1
3H, H3,4,5), 8.33 (d, 1H, H6), J5,6ˆ5.0 Hz (the H NMR
data are in accordance with those of the literature).12e
Anal. Calcd for C8H11NO (137.18): C, 70.04; H, 8.08; N,
10.21. Found: C, 70.23; H, 7.85; N, 10.33%.
2-Benzoylpyridine (2h). Procedure A, using benzoyl
chloride as an electrophile (in this case, the reaction mixture
was cooled to Ϫ70ЊC before addition of the electrophile and
slowly warmed to room temperature) gave 11% (CH2Cl2) of
2h when triethylamine (1.4 mL, 1.0 g, 10 mmol) was added
before the electrophile: mp 39–40ЊC (Lit. 12j mp 39.5–
3-Substituted pyridines 4a–m: general procedure B
iPrMgCl (10 mmol) was added to 3 (0.96 mL, 1.6 g,
10 mmol) in THF (10 mL) at rt. After 1 h, the electrophile
(10 mmol) was added. After 18 h at rt, water (50 mL) was
added. Extraction with CH2Cl2 (3×20 mL), drying over
MgSO4 and column chromatography on silica gel (eluent)
afforded 4a–m.
1
41ЊC); H NMR (CDCl3) d 7.5 (m, 5H, Ph), 8.1 (m, 3H,
H3,4,5), 8.65 (dd, 1H, H6), J4,6ˆ2.0, J5,6ˆ5.0 Hz (the NMR
data are in accordance with those of the literature).12k Anal.
Calcd for C12H9NO (183.21): C, 78.67; H, 4.95; N, 7.65.
Found: C, 78.38; H, 4.85; N, 7.37%.
a-Phenyl-3-pyridinemethanol (4a). Procedure B, using
benzaldehyde as an electrophile gave 84% (CH2Cl2), 93%
when triethylamine (1.4 mL, 1.0 g, 10 mmol) was added
before the electrophile, of 4a: mp 67–69ЊC (Lit. 13a mp
2-Acetylpyridine (2i). Procedure A, using acetyl chloride
as an electrophile (in this case, the reaction mixture was
cooled to Ϫ70ЊC before addition of the electrophile and
slowly warmed to room temperature) gave 15% (CH2Cl2/
1
62.5–63.5ЊC); H NMR (CDCl3) d 5.00 (s, 1H, OH), 5.81
1
AcOEt, 80:20) of 2i: oil; H NMR (CDCl3) d 2.67 (s, 3H,
(s, 1H, CHOH), 7.15 (dd, 1H, H5), 7.2 (m, 5H, Ph), 7.71
(ddd, 1H, H4), 8.20 (dd, 1H, H6), 8.37 (d, 1H, H2),
J2,4ˆJ4,6ˆ1.7, J5,6ˆ4.8, J4,5ˆ7.9 Hz; 13C NMR (CDCl3) d
CH3), 7.02 (m, 1H, H5), 7.33 (d, 1H, H3), 7.60 (m, 1H, H4),
8.48 (dd, 1H, H6), J4,6ˆ1.9, J3,4ˆ4.7, J5,6ˆ5.0 Hz; 13C NMR
(CDCl3) d 25.6 (CH3), 121.4 (C3), 127.0 (C5), 136.7 (C4),
148.8 (C6), 153.4 (C2), 199.8 (CO) (the NMR data are in
accordance with those of the literature);12l IR (neat) n 3353,
3183, 1664, 1636, 1610, 1382, 669 cmϪ1. Anal. Calcd for
C7H7NO (121.14): C, 69.41; H, 5.82; N, 11.56. Found: C,
69.48; H, 5.87; N, 11.41%.
0
0
0
73.4 (CHOH), 123.4 (C5), 126.4 (C2 ,6 ), 127.6 (C4 ), 128.4
0
0
0
(C3 ,5 ), 135.4 (C4), 140.1 (C3), 143.3 (C1 ), 147.6 (C6), 147.7
(C2); IR (KBr) n 3155, 2852, 2668, 1592, 1578, 1495, 1476,
1451, 1424, 1332, 1052, 1038, 1024, 759, 713, 699 cmϪ1
.
Anal. Calcd for C12H11NO (185.23): C, 77.81; H, 5.99; N,
7.56. Found: C, 77.54; H, 6.11; N, 7.40%.
2-(Phenylthio)pyridine (2j). Procedure A, using diphenyl
disulfide as an electrophile gave 45% (CH2Cl2/Et2O, 90:10)
of 2j when triethylamine (1.4 mL, 1.0 g, 10 mmol) was
a-(2,6-Dichlorophenyl)-3-pyridinemethanol (4b). Pro-
cedure B, using 2,6-dichlorobenzaldehyde as an electrophile
gave 74% (CH2Cl2) of 4b: mp 96–98ЊC (13b mp 96–98ЊC);
1H NMR (CDCl3) d 6.50 (s, 1H, OH), 6.64 (s, 1H, CHOH),
7.0 (m, 4H, H5, Ph), 7.71 (d, 1H, H4), 8.20 (d, 1H, H6), 8.33
1
added before the electrophile: oil; H NMR (CDCl3) d
6.76 (d, 1H, H3), 7.0 (m, 3H, H5, Ph), 7.3 (m, 3H, Ph),
1
1
8.2 (m, 2H, H4,6), J3,4ˆ4.9 Hz (the H NMR data are in
(s, 1H, H2), J5,6ˆ3.7, J4,5ˆ7.4 Hz (the H NMR data are in
accordance with those of the literature);12m 13C NMR
accordance with those of the literature);13b 13C NMR
0
(CDCl3) d 119.5 (C5), 120.9 (C3), 128.7 (C4 ), 129.3
0
0
(CDCl3) d 68.9 (CHOH), 123.1 (C5), 129.2 (C3 ,5 ), 129.5
0
0
0
0
0
(C3 ,5 ), 130.5 (C1 ), 134.5 (C2 ,6 ), 136.4 (C4), 149.1 (C6),
161.0 (C2); IR (neat) n 3048, 1953, 1574, 1142, 1024,
751 cmϪ1. Anal. Calcd for C11H9NS (187.27): C, 70.55;
H, 4.84; N, 7.48; S, 17.12. Found: C, 70.36; H, 4.74; N,
7.60; S, 17.80%.
0
0
0
0
(C4 ), 134.1 (C4), 135.2 (C2 ,6 ), 137.3 (C3), 138.2 (C1 ),
146.2 (C2), 146.7 (C6); IR (KBr) n 3160, 2877, 1595,
1579, 1561, 1344, 1292, 1196, 1182, 1088, 1057, 1029,
868, 843, 775, 762, 733, 709, 643 cmϪ1. Anal. Calcd for
C12H9Cl2NO (254.12): C, 56.72; H, 3.57; N, 5.51. Found:
C, 56.70; H, 3.65; N, 5.65%.
2-(Methylthio)pyridine (2k). Procedure A, using dimethyl
disulfide as an electrophile gave 40% (CH2Cl2/Et2O, 90:10)
of 2k when triethylamine (1.4 mL, 1.0 g, 10 mmol) was
Bis(3-pyridine)methanol (4c). Procedure B, using
3-formylpyridine as an electrophile gave 32% (CH2Cl2/
AcOEt, 50:50), 40% when triethylamine (1.4 mL, 1.0 g,
10 mmol) was added before the electrophile, of 4c: viscous
1
added before the electrophile: oil; H NMR (CDCl3) d
2.35 (s, 3H, CH3), 6.70 (m, 1H, H3), 6.95 (m, 1H, H5),
7.30 (m, 1H, H4), 8.24 (d, 1H, H6), J5,6ˆ4.0 Hz; 13C NMR
(CDCl3) d 12.2 (CH3), 118.1 (C5), 120.5 (C3), 134.8 (C4),
148.5 (C6), 159.0 (C2) (the NMR data are in accordance with
1
oil; H NMR (CDCl3) d 5.00 (s, 1H, OH), 5.23 (s, 1H,
CHOH), 6.95 (dd, 1H, H5), 7.45 (d, 1H, H4), 8.05 (d, 1H,
1
H6), 8.23 (s, 1H, H2), J5,6ˆ4.0, J4,5ˆ7.6 Hz (the H NMR

´
F. Trecourt et al. / Tetrahedron 56 (2000) 1349–1360
1355
data are in accordance with those of the literature);13b 13
C
a,a-Diethyl-3-pyridinemethanol (4h). Procedure B, using
pentan-3-one as an electrophile gave 58% (CH2Cl2/Et2O,
80:20), 16% when triethylamine (1.4 mL, 1.0 g, 10 mmol)
was added before the electrophile, of 4h: oil; H NMR
(CDCl3) d 0.63 (t, 6H, 2CH3), 1.59 (q, 4H, 2CH2), 6.95 (s,
NMR (CDCl3) d 70.7 (CHOH), 123.4 (C5), 134.4 (C4),
139.5 (C3), 147.2 (C2), 147.8 (C6); IR (KBr) n 3243,
1660, 1584, 1581, 1479, 1428, 1059, 1028, 808,
714 cmϪ1. Anal. Calcd for C11H10N2O (186.22): C, 70.95;
H, 5.41; N, 15.04. Found: C, 71.10; H, 5.35; N, 14.86%.
1
1H, OH), 7.12 (dd, 1H, H5), 7.58 (d, 1H, H4), 8.18 (d, 1H,
1
H6), 8.40 (s, 1H, H2), J5,6ˆ4.8, J4,5ˆ7.9 Hz (the H NMR
a-(3-Pyridyl)-2-pyridinemethanol (4d). Procedure B,
using 2-formylpyridine as an electrophile gave 46%
(CH2Cl2/AcOEt, 50:50) of 4d: viscous oil; 1H NMR
(CDCl3) d 5.60 (s, 1H, CHOH), 6.10 (s, 1H, OH), 6.8 (m,
data are in accordance with those of the literature);13f 13C
NMR (CDCl3) d 7.5 (CH3), 34.4 (CH2), 63.4 (COH), 122.9
(C5), 134.3 (C4), 142.0 (C3), 146.0 (C2), 146.4 (C6); IR
(neat) n 3204, 2968, 2937, 2880, 1580, 1460, 1419, 1376,
1098, 969, 898, 811, 715 cmϪ1. Anal. Calcd for C10H15NO
(165.24): C, 72.69; H, 9.15; N, 8.48. Found: C, 72.41; H,
9.43; N, 8.32%.
0
0
2H, H5,5 ), 7.25 (m, 2H, H3,4), 7.53 (d, 1H, H4 ), 7.95 (d, 1H,
0
0
H6 ), 8.05 (d, 1H, H6), 8.29 (s, 1H, H2 ), J5,6ˆ3.8, J5,6ˆ3.9,
J4,5ˆ7.5, J4,5ˆ7.6 Hz; 13C NMR (CDCl3) d 73.4 (CHOH),
0
120.4 (C3), 122.2 (C5), 123.2 (C5 ), 134.6 (C4), 136.9
0
0
0
0
(C4 ), 139.2 (C3 ), 147.5 (C6), 147.5 (C6 ), 148.0 (C2 ),
3-Benzoylpyridine (4i). Procedure B, using benzoyl
chloride as an electrophile gave 35% (CH2Cl2 and then
CH2Cl2/AcOEt, 50:50) when added at Ϫ70ЊC and the
mixture gently warmed to room temperature, of 4i: mp
161.8 (C2); IR (KBr) n 3270, 1667, 1594, 1476, 1435,
1062, 768, 713 cmϪ1
. Anal. Calcd for C11H10N2O
(186.22): C, 70.95; H, 5.41; N, 15.04. Found: C, 70.81; H,
5.50; N, 15.17%.
1
36–37ЊC (13g mp 36–38ЊC); H NMR (CDCl3) d 7.5 (m,
6H, H5, Ph), 8.10 (ddd, 1H, H4), 8.79 (dd, 1H, H6), 8.98 (d,
1H, H2), J2,4ˆJ4,6ˆ1.9, J5,6ˆ5.0, J4,5ˆ7.9 Hz (the 1H NMR
data are in accordance with those of the literature).13h Anal.
Calcd for C12H9NO (183.21): C, 78.67; H, 4.95; N, 7.65.
Found: C, 78.45; H, 5.11; N, 7.37%.
a-(tert-Butyl)-3-pyridinemethanol (4e). Procedure B,
using 2,2-dimethylpropanal as an electrophile gave 78%
(CH2Cl2/Et2O, 80:20) of 4e: mp 80–83ЊC (Lit. 13c mp
1
79–82ЊC); H NMR (CDCl3) d 0.63 (s, 9H, 3 CH3), 4.10
(s, 1H, CHOH), 5.82 (s, 1H, OH), 6.89 (dd, 1H, H5), 7.43 (d,
1H, H4), 7.95 (d, 1H, H6), 8.04 (s, 1H, H2), J5,6ˆ4.9,
J4,5ˆ7.6 Hz; 13C NMR (CDCl3) d 25.5 (CH3), 35.3
(C(CH3)3), 78.7 (CHOH), 122.4 (C5), 135.4 (C4), 138.6
(C3), 147.0 (C2), 148.1 (C6) (the NMR data are in
accordance with those of the literature);13c IR (KBr) n
3234, 2965, 2868, 1591, 1578, 1483, 1424, 1363, 1310,
1237, 1212, 1175, 1066, 1042, 1029, 1012, 815, 759, 716,
630 cmϪ1. Anal. Calcd for C10H15NO (165.24): C, 72.69; H,
9.15; N, 8.48. Found: C, 72.70; H, 9.32; N, 8.59%.
3-(Isobutyryl)pyridine (4j). Procedure B, using isobutyryl
chloride as an electrophile gave 12% (CH2Cl2 and then
CH2Cl2/AcOEt, 50:50) when added at Ϫ70ЊC and the
1
mixture gently warmed to room temperature, of 4j: oil; H
NMR (CDCl3) d 1.15 (d, 6H, 2CH3), 3.45 (sept, 1H,
CH(CH3)2), 7.35 (dd, 1H, H5), 8.16 (dd, 1H, H4), 8.70 (dd,
1H, H6), 9.12 (s, 1H, H2), J4,6ˆ1.8, J5,6ˆ5.1, JCH–CH3ˆ6.6,
J4,5ˆ7.9 Hz (the 1H NMR data are in accordance with those
of the literature);13b 13C NMR (CDCl3) d 19.2 (CH3), 36.3
(CH(CH3)2), 124.1 (C5), 131.7 (C3), 136.1 (C4), 150.1 (C2),
153.6 (C6), 203.5 (CO); IR (neat) n 3363, 2972, 2933, 2874,
1699, 1585, 1467, 1418, 1385, 1237, 981, 703 cmϪ1. Anal.
Calcd for C9H11NO (149.19): C, 72.46; H, 7.43; N, 9.39.
Found: C, 72.19; H, 7.40; N, 9.15%.
a-Methyl-3-pyridinemethanol (4f).13d Procedure B, using
acetaldehyde as an electrophile gave 51% (CH2Cl2), 14%
when triethylamine (1.4 mL, 1.0 g, 10 mmol) was added
before the electrophile, 74% when CH3CHO (5.6 mL,
4.4 g, 100 mmol) was added at Ϫ20ЊC, of 4f: oil; 1H
NMR (CDCl3) d 1.21 (d, 1H, CH3), 4.60 (s, 1H, CHOH),
6.88 (s, 1H, OH), 6.89 (dd, 1H, H5), 7.43 (dd, 1H, H4), 8.00
(dd, 1H, H6), 8.15 (s, 1H, H2), J4,6ˆ1.9, J5,6ˆ4.7, J4,5ˆ7.9,
JCH3–CHˆ6.6 Hz; 13C NMR (CDCl3) d 24.9 (CH3), 66.6
(CHOH), 123.2 (C5), 133.4 (C4), 142.0 (C3), 146.4 (C2),
147.1 (C6); IR (neat) n 3346, 2971, 2928, 1728, 1667,
1595, 1591, 1427, 1370, 1091, 714 cmϪ1. Anal. Calcd for
C7H9NO (123.16): C, 68.27; H, 7.37; N, 11.37. Found: C,
67.99; H, 7.66; N, 11.08%.
3-(Methylthio)pyridine (4k). Procedure B, using dimethyl
disulfide as an electrophile gave 49% (CH2Cl2/Et2O, 95:5),
58% when triethylamine (1.4 mL, 1.0 g, 10 mmol) was
added before the electrophile, of 4k: oil; 1H NMR
(CDCl3) d 2.98 (s, 3H, CH3), 6.70 (dd, 1H, H5), 7.05
(ddd, 1H, H4), 7.91 (dd, 1H, H6), 8.00 (d, 1H, H2), J4,6ˆ
1.5, J2,4ˆ2.0, J5,6ˆ4.8, J4,5ˆ8.0 Hz; 13C NMR (CDCl3) d
14.9 (CH3), 122.9 (C5), 133.3 (C4), 135.0 (C3), 145.5 (C6),
147.2 (C2) (the NMR data are in accordance with those of
the literature);13i IR (neat) n 3396, 3036, 2921, 1559, 1469,
1435, 1404, 1109, 1018, 793, 705 cmϪ1. Anal. Calcd for
C6H7NS (125.19): C, 57.56; H, 5.64; N, 11.19. Found: C,
57.37; H, 5.91; N, 11.37%.
a,a-Diphenyl-3-pyridinemethanol (4g). Procedure B,
using benzophenone as an electrophile gave 51% (CH2Cl2/
AcOEt, 80:20) of 4g: mp 115–116ЊC (Lit. 13e mp 115–
1
117ЊC); H NMR (CDCl3) d 6.60 (s, 1H, OH), 7.12 (dd,
1H, H5), 7.2 (m, 10H, Ph), 7.71 (d, 1H, H4), 8.08 (d, 1H,
3-Iodopyridine (4l). Procedure B, using iodine as an
electrophile gave 78% (CH2Cl2) of 4l: mp 52–53ЊC (Lit.
H6), 8.20 (s, 1H, H2), J5,6ˆ4.8, J4,5ˆ8.5 Hz; 13C NMR
1
0
(CDCl3) d 80.0 (COH), 122.8 (C5), 127.2 (2C1 ), 127.9
13j mp 52.3–53ЊC); H NMR (CDCl3) dˆ7.16 (dd, 1H,
(2C2,6, 2 C3,5), 135.9 (C4), 143.3 (C3), 146.4 (2C4), 146.9
(C2), 148.6 (C6); IR (KBr) n 3152, 2800, 1588, 1489, 1428,
1223, 1163, 1039, 1022, 897, 775, 758, 704 cmϪ1. Anal.
Calcd for C18H15NO (261.33): C, 82.73; H, 5.79; N, 5.36.
Found: C, 82.44; H, 5.95; N, 5.20%.
H5), 8.09 (ddd, 1H, H4), 8.63 (dd, 1H, H6), 8.92 (d, 1H,
H2), J4,6ˆ1.4, J2,4ˆ1.9, J5,6ˆ1.7, J4,5ˆ8.2 Hz (the 1H
NMR data are in accordance with those of the literature);13k
13C NMR (CDCl3): d 93.5 (C3), 125.1 (C5), 144.1 (C4),
148.0 (C6), 155.7 (C2). Anal. Calcd for C5H4IN (205.00):

´
F. Trecourt et al. / Tetrahedron 56 (2000) 1349–1360
1356
C, 29.30; H, 1.97; N, 6.83. Found: C, 29.60; H, 1.87; N,
6.98%.
140.1 (C2), 149.2 (C2,6), 152.9 (C4); IR (KBr) n 3152, 2845,
1605, 1411, 1334, 1273, 1053, 1003, 828, 743 cmϪ1. Anal.
Calcd for C16H13NO (235.29): C, 81.68; H, 5.57; N, 5.95.
Found: C, 81.63; H, 5.62; N, 6.25%.
Bis(3-pyridyl)mercury (4m). Procedure B, using mercury(II)
bromide as an electrophile gave 80% of 4m, after filtration
of the reaction mixture, washing with water (100 mL) and
a-Pentyl-4-pyridinemethanol (6c).14c Procedure C, using
1
1
drying: mp 238ЊC (13l mp 239ЊC); H NMR (DMSO-d6) d
hexanal as an electrophile gave 42% (Et2O) of 6c: oil; H
7.32 (dd, 1H, H5), 7.94 (m, 1H, H4), 8.33 (dd, 1H, H6), 8.59
(dd, 1H, H2), J2,4ˆ1.5, J4,6ˆ1.7, J5,6ˆ4.8, J4,5ˆ7.3,
J2,Hgˆ60, J4,Hgˆ109 Hz; 13C NMR (DMSO-d6) d 124.4
(C5), 146.1 (C4), 148.3 (C6), 157.8 (C2), 164.7 (C3); IR
(KBr) n 3448, 3020, 1654, 1560, 1464, 1393, 1294, 1022,
797, 714, 623, 380 cmϪ1. Anal. Calcd for C10H8HgN2
(356.78): C, 33.67; H, 2.26; N, 7.85. Found: C, 33.90; H,
2.16; N, 7.59%.
NMR (CDCl3) d 0.78 (t, CH3, 3H), 1.5 (m, 8H, CH2), 4.57
(t, 1H, CHOH), 5.05 (s, 1H, OH), 7.18 (d, 2H, H3,5), 8.27 (d,
2H, H2,6), J2,3ˆ5.1, JCH3–CH2ˆ6.3, JCH–CH2ˆ6.4 Hz; 13C
NMR (CDCl3) d 14.4 (CH3), 22.9 (CH2), 25.6 (CH2), 32.0
(CH2), 39.3 (CH2), 72.8 (CHOH), 121.5 (C3,5), 149.3 (C2,6),
155.7 (C4); IR (neat) n 3400, 2956, 2931, 2859, 1605, 1416,
1065, 1004, 825 cmϪ1. Anal. Calcd for C11H17NO (179.26):
C, 73.70; H, 9.56; N, 7.81. Found: C, 73.57; H, 9.29; N,
8.08%.
2-Chloro-a-(2-methoxyphenyl)-3-pyridinemethanol
(24). Procedure B was used, starting from 23 (1.9 g,
10 mmol). Using o-anisaldehyde as an electrophile gave
74% (CH2Cl2) of 24: mp 123–124ЊC (Lit. 10 mp 124ЊC);
1H NMR (CDCl3) d 3.85 (s, 3H, OCH3), 4.48 (d, 1H, OH),
6.35 (d, 1H, CHOH), 7.1 (m, 5H, H5, Ph), 7.90 (dd, 1H, H4),
8.25 (dd, 1H, H6), J4,6ˆ1.9, JCH–OHˆ4.0, J5,6ˆ5.0,
J4,5ˆ7.5 Hz; 13C NMR (CDCl3) d 54.3 (OCH3), 66.3
a-Isopropyl-4-pyridinemethanol (6d).14d Procedure C,
using isobutyraldehyde as an electrophile gave 39%
1
(CH2Cl2/AcOEt, 80:20) of 6d: oil; H NMR (CDCl3) d
0.81 (2d, 2CH3, 6H), 1.86 (m, 1H, CH), 4.34 (d, 1H,
CHOH), 4.80 (s, 1H, OH), 7.16 (d, 2H, H3,5), 8.28 (d, 2H,
H2,6), J2,3ˆ4.7, JCH–CH2ˆ5.7, JCH3–CHˆ6.8 Hz; 13C NMR
(CDCl3) d 17.7 (CH3), 19.3 (CH3), 35.4 (CH), 77.9
(CHOH), 122.3 (C3,5), 149.2 (C2,6), 154.1 (C4); IR (neat)
n 3234, 2962, 2932, 2873, 1605, 1416, 1048, 1019,
1004, 783 cmϪ1. Anal. Calcd for C9H13NO (151.21):
C, 71.49; H, 8.67; N, 9.26. Found: C, 71.38; H, 8.44; N,
8.96%.
0
0
0
(CHOH), 109.7 (C3 ), 119.6 (C5 ), 121.6 (C5), 126.7 (C6 ),
0
0
128.2 (C4 ), 128.9 (C1 ), 136.7 (C4), 136.9 (C3), 146.9 (C6),
0
148.9 (C2), 155.8 (C2 ); IR (KBr) n 3340, 1600, 1590,
1580, 1570 cmϪ1. Anal. Calcd for C13H12ClNO2 (249.70):
C, 62.53; H, 4.84; N, 5.61. Found: C, 62.29; H, 4.90; N,
5.63%.
a,a-Diphenyl-4-pyridinemethanol (6e). Procedure C,
using benzophenone as an electrophile gave 29% (AcOEt)
of 6e: mp 237–239ЊC (14e mp 238–239ЊC); 1H NMR
(DMSO-d6) d 6.75 (s, 1H, OH), 7.20 (d, 2H, H3,5), 7.5
(m, 10H, Ph), 8.53 (d, 2H, H2,6), J2,3ˆ5.6 Hz (the 1H
NMR data are in accordance with those of the literature);14f
IR (KBr) n 3085, 2789, 1659, 1596, 1445, 1427, 1278,
. Anal. Calcd for C18H15NO
(261.33): C, 82.73; H, 5.79; N, 5.36. Found: C, 82.91; H,
5.87; N, 5.08%.
4-Substituted pyridines 6a–g: general procedure C
Compound 5a (1.9 g, 10 mmol) was treated with 5%
aqueous Na2CO3 (50 mL). Extraction with Et2O
(3×20 mL), drying over MgSO4 and removal of the solvent
afforded 5b, which was immediately dissolved in THF
(10 mL). iPrMgCl (10 mmol) and after 1 h 30, the electro-
phile were added at rt. After 18 h, water (50 mL) was added.
Extraction with CH2Cl2 (3×20 mL), drying over MgSO4
and column chromatography on silica gel (eluent) afforded
6a–g.
1050, 1002, 698 cmϪ1
4-(Phenylthio)pyridine (6f). Procedure C, using diphenyl
disulfide as an electrophile gave 45% (CH2Cl2/Et2O, 90:10)
when triethylamine (1.4 mL, 1.0 g, 10 mmol) was added
a-Phenyl-4-pyridinemethanol (6a). Procedure C, using
1
before the electrophile, of 6f: oil; H NMR (CDCl3) d
benzaldehyde as an electrophile gave 64% (CH2Cl2/Et2O,
1
6.85 (AA0XX0, 2H, H3,5), 7.4 (m, 3H, Ph), 7.5 (m, 2H,
80:20) of 6a: mp 125ЊC (14a mp 125–126.5ЊC); H NMR
1
Ph), 8.26 (AA0XX0, 2H, H2,6), J2,3ˆ5.3 Hz (the H NMR
(CDCl3) d 5.71 (s, 1H, CHOH), 6.10 (s, 1H, OH), 7.2 (m,
data are in accordance with those of the literature);14g 13C
NMR (CDCl3) d 121.2 (C3,5), 129.8 (C1), 130.1 (C4), 130.3
(C3,5), 135.6 (C2,6), 149.9 (C2,6), 150.7 (C4); IR (neat) n
3400, 3050, 3032, 1573, 1541, 1477, 1440, 1407, 1066,
804, 751, 706, 691 cmϪ1. Anal. Calcd for C11H9NS
(187.27): C, 70.55; H, 4.84; N, 7.48; S, 17.12. Found: C,
70.26; H, 4.86; N, 7.42; S, 16.82%.
1
7H, H3,5, Ph), 8.20 (d, 2H, H2,6), J2,3ˆ5.3 Hz (the H NMR
data are in accordance with those of the literature);14b 13C
0
0
NMR (CDCl3) d 74.3 (CHOH), 121.4 (C3,5), 126.7 (C2 ,6 ),
0
0
0
0
127.8 (C4 ), 128.5 (C3 ,5 ), 143.1 (C1 ), 146.7 (C2,6), 153.9
(C4); IR (KBr) n 3132, 2825, 1599, 1453, 1260, 1094, 1046,
1002, 787, 762, 702, 658, 604 cmϪ1. Anal. Calcd for
C12H11NO (185.23): C, 77.81; H, 5.99; N, 7.56. Found: C,
77.55; H, 5.79; N, 7.28%.
4-Iodopyridine (6g). Procedure C, using iodine as an
electrophile gave 51% (CH2Cl2) of 6g: mp 98–100ЊC,
a-(2-Naphthyl)-4-pyridinemethanol (6b). Procedure C,
1
dec. (Lit. 14h mp 100ЊC, dec.); H NMR (CDCl3) d 7.72
using 2-naphthaldehyde as an electrophile gave 40%
(d, 1H, H3,5), 8.29 (d, 1H, H2,6), J2,3ˆ5.5 Hz; 13C NMR
(CDCl3) d 105.1 (C4), 132.8 (C3,5), 150.0 (C2,6) (the NMR
data are in accordance with those of the literature).14i Anal.
Calcd for C5H4IN (205.00): C, 29.30; H, 1.97; N, 6.83.
Found: C, 29.40; H, 1.85; N, 6.98%.
1
(CH2Cl2/AcOEt, 80:20) of 6b: mp 149–150ЊC; H NMR
(CDCl3) d 4.70 (s, 1H, OH), 5.90 (s, 1H, CHOH), 7.6 (m,
9H, H3,5, naphthyl), 8.37 (d, 2H, H2,6), J2,3ˆ5.9 Hz; 13C
NMR (CDCl3) d 74.7 (CHOH), 121.3 (C3,5), 124.4, 125.5,
126.1, 126.3, 127.6, 127.8, 128.6, 132.9 and 133.0 (Ca,b),

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F. Trecourt et al. / Tetrahedron 56 (2000) 1349–1360
1357
2-Bromo-6-substituted pyridines 8a–e
a-Phenyl-2-(6-d)pyridinemethanol (9a). Using benzalde-
hyde as an electrophile gave 66%, 100% d (CH2Cl2/Et2O,
90:10) of 9a: mp 72–73ЊC; 1H NMR (CDCl3) d 5.87 (s, 1H,
CHOH), 6.10 (s, 1H, OH), 7.3 (m, 8H, H3,4,5, Ph); 13C NMR
(CDCl3) d 76.6 (CHOH), 122.3 (C3), 123.4 (C5), 128.1
(C2,6), 128.7 (C4), 129.6 (C3,5), 138.2 (C4), 144.6 (C1),
150.0 (C6), 163.2 (C2); IR (KBr) n 3340, 3112, 3094,
Procedure A was used, starting from 7 (2.4 g, 10 mmol).
2-Bromo(6-d)pyridine (8a). Using D2O as an electrophile
gave 95%, 100% d (CH2Cl2) of 8a: oil; 1H NMR (CDCl3) d
7.27 (d, 1H, H5), 7.50 (d, 1H, H3), 7.56 (t, 1H, H4), J4,5ˆ7.0,
J3,4ˆ7.9 Hz (the 1H NMR data are in accordance with those
of the literature);15a 13C NMR (CDCl3) d 122.8 (C5), 128.5
(C3), 138.8 (C4), 142.4 (C2), 150.0 (C6); IR (neat) n 3051,
1594, 1494, 1435, 1050 cmϪ1
.
Anal. Calcd for
C12H10DNO (186.23): C, 77.39; “H”,15b 6.01; N, 7.52.
Found: C, 77.66; “H”, 6.12; N, 7.47%.
1571, 1561, 1447, 1414, 1106, 1076, 987, 759, 700 cmϪ1
.
Anal. Calcd for C5H3BrDN (159.01): C, 37.77; “H”,15b 2.61;
N, 8.81. Found: C, 37.52; “H”, 2.83; N, 8.90%.
2-Iodo(6-d)pyridine (9b). Using iodine as an electrophile
(in this case, the reaction mixture was treated with 50 mL of
a 0.5 N aqueous sodium thiosulfate solution instead of
water) gave 42%, 100% d (CH2Cl2/Et2O, 95:5) of 9b: oil;
bp 92ЊC/15 mm Hg; 1H NMR (CDCl3) d 7.5 (m, 3H, H3,4,5);
13C NMR (CDCl3) d 118.1 (C2), 122.7 (C5), 134.5 (C3),
137.3 (C4), 150.4 (C6); IR (neat) n 1553, 1445, 1411,
755 cmϪ1. Anal. Calcd for C5H3DIN (206.00): C, 29.15;
‘H’,15b 2.01; N, 6.80. Found: C, 28.92; “H”, 2.14; N, 6.95%.
6-Bromo-a-phenyl-2-pyridinemethanol (8b). Using
benzaldehyde as an electrophile gave 42% (CH2Cl2) of
1
8b: oil; H NMR (CDCl3) d 4.59 (s, 1H, CHOH), 4.90 (s,
1H, OH), 7.3 (m, 8H, H3,4,5, Ph); 13C NMR (CDCl3) d 75.5
(CHOH), 120.4 (C5), 127.2 (C3), 127.4 (C2,6), 128.5 (C4),
0
129.1 (C3,5), 139.7 (C4), 141.2 (C1 ), 142.6 (C2), 164.8 (C6);
IR (neat) n 3380, 2874, 1582, 1557, 1495, 1434, 1123, 1046,
986, 784, 737, 700 cmϪ1. Anal. Calcd for C12H10BrNO
(264.12): C, 54.57; H, 3.82; N, 5.30. Found: C, 54.39; H,
3.98; N, 5.04%.
3-Bromo-5-substituted pyridines 11a–b
Procedure B was used, starting from 10 (2.4 g, 10 mmol).
3-Bromo(5-d)pyridine (11a). Using D2O as an electrophile
gave 82%, 100% d (CH2Cl2/Et2O, 90:10) of 11a: oil; H
6-Bromo-2-pyridyltrimethylsilane (8c). Using chloro-
trimethylsilane as an electrophile gave 74% (CH2Cl2/Et2O,
90:10) of 8c: oil; 1H NMR (CDCl3) d 0.24 (s, 9H, Si(CH3)3),
1
NMR (CDCl3) d 7.76 (s, 1H, H4), 8.51 (s, 1H, H6), 8.68
(s, 1H, H2); 13C NMR (CDCl3) d 121.3 (C3), 125.0 (C5),
139.0 (C4), 148.1 (C6), 151.4 (C2); IR (KBr) n 3043, 1571,
1463, 1413, 1095, 1086, 1007, 792, 700, 612 cmϪ1. Anal.
Calcd for C5H3BrDN (159.01): C, 37.77; ‘H’,15b 2.61; N,
8.81. Found: C, 37.60; “H”, 2.80; N, 8.95%.
1
7.33 (m, 3H, H3,4,5) (the H NMR data are in accordance
with those of the literature);15d 13C NMR (CDCl3) d 0.0
(Si(CH3)3), 129.2 (C3), 129.2 (C5), 138.3 (C4), 145.3 (C6),
170.0 (C2); IR (neat) n 2958, 2926, 1542, 1419, 1370, 1249,
1107, 842, 757, 748 cmϪ1. Anal. Calcd for C8H12BrNSi
(230.18): C, 41.74; H, 5.25; N, 6.09. Found: C, 41.52; H,
5.32; N, 5.89%.
5-Bromo-a-phenyl-3-pyridinemethanol (11b). Using
benzaldehyde as an electrophile gave 76% (CH2Cl2) of
11b: viscous oil; 1H NMR (CDCl3) d 5.66 (s, 1H,
CHOH), 5.94 (s, 1H, OH), 7.2 (m, 5H, Ph), 7.90 (s, 1H,
H4), 8.20 (s, 1H, H2), 8.21 (s, 1H, H6); 13C NMR (CDCl3)
d 72.1 (CHOH), 120.0 (C5), 125.8 (C2,6), 127.3 (C4), 128.0
(C3,5), 136.2 (C4), 141.2 (C3), 142.0 (C1), 144.9 (C2), 148.0
(C6); IR (neat) n 3365, 2872, 1454, 1422, 1045, 1023,
700 cmϪ1. Anal. Calcd for C12H10BrNO (264.12): C,
54.57; H, 3.82; N, 5.30. Found: C, 54.85; H, 3.78; N, 5.15%.
6-Bromo-2-(methylthio)pyridine (8d). Using dimethyl
disulfide as an electrophile gave 45% (CH2Cl2/Et2O, 95:5)
when triethylamine (1.4 mL, 1.0 g, 10 mmol) was added
1
before the electrophile, of 8d: oil; H NMR (CDCl3) d
2.48 (s, 3H, SCH3), 7.04 (2 d, 2H, H3,5), 7.23 (t, 1H, H4)
1
(the H NMR data are in accordance with those of the
literature);15d 13C NMR (CDCl3) d 13.9 (SCH3), 120.5
(C3), 123.3 (C5), 138.2 (C4), 142.0 (C6), 161.5 (C2); IR
(neat) n 2925, 1568, 1537, 1411, 1384, 1158, 1116, 770,
648 cmϪ1. Anal. Calcd for C6H6BrNS (204.09): C, 35.31; H,
2.96; N, 6.86; S, 15.71. Found: C, 35.44; H, 3.18; N, 6.96; S,
15.52%.
3-Bromo-4-chloropyridine (14).16a The foregoing pro-
cedure, applied to 13 instead of 10, using H2O as an
electrophile gave 99% (CH2Cl2/cyclohexane, 25:75) of 14:
mp 18ЊC; bp 94ЊC/20 mm Hg; 1H NMR (CDCl3) d 7.33 (d,
1H, H5), 8.30 (d, 1H, H6), 8.59 (s, 1H, H2), J5–6ˆ5.2 Hz; 13
C
2-Bromo-6-iodopyridine (8e). Using iodine as an electro-
phile gave 90% (CH2Cl2/Et2O, 90:10) of 8e: mp 134ЊC; 1H
NMR (DMSO-d6) d 7.34 (dd, 1H, H4), 7.57 (d, 1H, H5), 7.78
(d, 1H, H3), J4,5ˆ7.7, J3,4ˆ8.0 Hz; 13C NMR (DMSO-d6) d
117.6 (C6), 128.0 (C5), 134.6 (C3), 140.6 (C2), 141.4 (C4); IR
(KBr) n 1654, 1537, 1434, 1409, 1128, 1026 cmϪ1. Anal.
Calcd for C5H3BrIN (283.89): C, 21.15; H, 1.07; N, 4.93.
Found: C, 20.98; H, 1.19; N, 4.99%.
NMR (CDCl3) d 121.0 (C3), 125.0 (C5), 143.5 (C4), 148.5
(C2), 152.5 (C6) (the NMR data are in accordance with those
of the literature);16b IR (neat) n 2926, 2855, 2367, 1598,
1568, 1450, 1267, 828 cmϪ1. Anal. Calcd for C5H3BrClN
(192.44): C, 31.21; H, 1.57; N, 7.28. Found: C, 30.95; H,
1.39; N, 7.31%.
3,5-Disubstituted pyridines 12a–b: general procedure D
2-Substituted (6-d)pyridines 9a–b
iPrMgCl (10 mmol) was added to 10 (2.4 g, 10 mmol) in
THF (10 mL) at rt. After 1 h, the first electrophile
(10 mmol) was added. After 18 h at rt, iPrMgCl
(10 mmol) was added to the reaction mixture. The second
Procedure A was used, starting from 8a (0.95 mL, 1.6 g,
10 mmol).

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F. Trecourt et al. / Tetrahedron 56 (2000) 1349–1360
1358
electrophile (10 mmol) was added 1 h later. After 18 h at rt,
water (50 mL) was added. Extraction with CH2Cl2
(3×20 mL), drying over MgSO4 and column chromato-
graphy on silica gel (eluent) afforded 12a–b.
2-Bromo-3-iodopyridine (17b). Using iodine as an electro-
phile gave 80% (CH2Cl2/cyclohexane, 25:75) of 17b: mp
95–97ЊC; H NMR (CDCl3) d 7.02 (dd, 1H, H5), 8.08 (dd,
1H, H4), 8.30 (dd, 1H, H6), J4,6ˆ1.7, J5,6ˆ4.6, J3,4ˆ7.8 Hz;
13C NMR (CDCl3) d 99.4 (C3), 123.3 (C5), 148.0 (C2), 148.3
(C4), 148.6 (C6); IR (KBr) n 1724, 1550, 1380, 1247, 1124,
1052, 1006, 794 cmϪ1. Anal. Calcd for C5H3BrIN (283.89):
C, 21.15; H, 1.07; N, 4.93. Found: C, 20.94; H, 1.26; N,
5.05%.
1
a,a0-Diphenyl-3,5-pyridinedimethanol (12a). Procedure
D, using benzaldehyde as an electrophile gave 49%
(CH2Cl2/AcOEt, 80:20) of 12a: viscous oil; 1H NMR
(DMSO-d6) d 5.85 (s, 2H, CHOH), 6.25 (s, 2H, OH), 7.3
(m, 10H, Ph), 7.89 (s, 1H, H4), 8.53 (s, 2H, H2,6), JCH–
ˆ3.1 Hz; 13C NMR (DMSO-d6) d 72.7 (2CHOH),
2-Bromo-5-substituted pyridines 19a–c
OH
126.6 (2C2,6), 127.4 (2C4), 128.7 (2C3,5), 134.3 (C4), 140.9
(2 C1), 141.3 (C3,5), 145.2 (C2,6); IR (KBr) n 3400, 2830,
Procedure B was used, starting from 18 (2.4 g, 10 mmol).
2-Bromo(5-d)pyridine (19a). Using D2O as an electrophile
1648, 1590, 1493, 1453, 1433, 1043, 1025, 757, 700 cmϪ1
.
Anal. Calcd for C19H17NO2 (291.35): C, 78.33; H, 5.88; N,
4.81. Found: C, 78.06; H, 5.59; N, 4.75%.
1
gave 64%, 100% d (CH2Cl2/Et2O, 80:20) of 19a: oil; H
NMR (CDCl3) d 7.51 (d, 1H, H3), 7.57 (d, 1H, H4), 8.39
(s, 1H, H6), J3,4ˆ8.0 Hz; 13C NMR (CDCl3) d 122.0 (C5),
128.6 (C3), 138.9 (C4), 142.6 (C2), 150.5 (C6); IR (KBr)
n 3052, 1571, 1561, 1448, 1414, 1106, 1077, 1042, 987,
759, 700 cmϪ1. Anal. Calcd for C5H3BrDN (159.01): C,
37.77; “H”,15b 2.61; N, 8.81. Found: C, 37.82; “H”, 2.89;
N, 8.71%.
a-Phenyl-5-(trimethylsilyl)-3-pyridinemethanol (12b).
Procedure D, using chlorotrimethylsilane and benzaldehyde
as electrophiles gave 52% (CH2Cl2/Et2O, 80:20) of 12b: mp
1
111–113ЊC; H NMR (CDCl3) d 0.01 (Si(CH3)3), 5.02 (s,
1H, OH), 5.50 (s, 1H, CHOH), 7.1 (m, 5H, Ph), 7.66 (s, 1H,
H4), 8.08 (2 s, 2H, H2,6); 13C NMR (CDCl3) d 0.0
(Si(CH3)3), 75.2 (CHOH), 127.9 (C2,6), 129.0 (C4), 129.9
(C3,5), 136.3 (C5), 140.5 (C3), 140.7 (C4), 145.0 (C1),
149.3 (C2), 153.2 (C6); IR (KBr) n 3136, 2953, 2894,
1570, 1456, 1440, 1395, 1252, 1226, 1039, 1028, 841,
754, 697 cmϪ1. Anal. Calcd for C15H19NOSi (257.41): C,
69.99; H, 7.44; N, 5.44. Found: C, 70.08; H, 7.23; N,
5.53%.
2-Bromo-a-phenyl-5-pyridinemethanol (19b).17a Using
benzaldehyde as an electrophile gave 86% (CH2Cl2) of
1
19b: mp 88–90ЊC; H NMR (CDCl3) d 5.00 (s, 1H, OH),
5.74 (s, 1H, CHOH), 7.2 (m, 5H, Ph), 7.33 (d, 1H, H3), 7.49
(d, 1H, H4), 8.11 (s, 1H, H6), J3,4ˆ8.2 Hz; 13C NMR
(CDCl3) d 72.9 (CHOH), 126.4 (C2,6), 127.8 (C4), 127.9
(C3), 128.6 (C3,5), 137.2 (C4), 139.2 (C5), 140.2 (C2),
142.6 (C1), 148.1 (C6); IR (KBr) n 3400, 3044, 2887,
1578, 1563, 1451, 1406, 1384, 1303, 1189, 1091, 1040,
1015, 812, 761, 737, 701 cmϪ1. Anal. Calcd for
C12H10BrNO (264.12): C, 54.57; H, 3.82; N, 5.30. Found:
C, 54.25; H, 3.69; N, 4.99%.
4-Chloro-a,a0-diphenyl-3,5-pyridinedimethanol
(15).
Procedure D, applied to 13 instead of 10, using benzalde-
hyde as an electrophile gave 74% (CH2Cl2/AcOEt, 90:10) of
1
15: mp 152–156ЊC; H NMR (DMSO-d6) d 6.10 (s, 2H,
OH), 6.27 (s, 2H, CHOH), 7.3 (m, 10H, Ph), 8.83 (s, 2H,
H2,6); 13C NMR (DMSO-d6) d 70.4/70.6 (2CHOH), 127.2
(2C2,6), 127.7 (2C4), 128.6 (2C3,5), 137.9 (C4), 139.7/139.2
(2C1), 143.2 (C3,5), 148.5/148.3 (C2,6), signals are doubled,
due to the presence of stereoisomers; IR (KBr) n 3401,
3030, 2816, 2683, 1577, 1454, 1419, 1241, 1159, 1076,
1048, 1028, 914, 833, 813, 763, 699 cmϪ1. Anal. Calcd
for C19H16ClNO2 (325.80): C, 70.05; H, 4.95; N, 4.30.
Found: C, 69.88; H, 5.02; N, 4.15%.
2-Bromo-5-iodopyridine (19c). Using iodine as an electro-
phile gave 82% (CH2Cl2/cyclohexane, 25:75) of 19c: mp
1
124–126ЊC (17b mp 125–126ЊC); H NMR (CDCl3) d 7.19
(d, 1H, H3), 7.83 (dd, 1H, H4), 8.50 (d, 1H, H6), J4,6ˆ2.3,
J3,4ˆ8.3 Hz; 13C NMR (CDCl3) d 91.7 (C5), 129.8 (C3),
141.2 (C2), 146.4 (C4), 155.9 (C6); IR (KBr) n 3018,
1544, 1439, 1354, 1085, 995, 828, 624, 477 cmϪ1. Anal.
Calcd for C5H3BrIN (283.89): C, 21.15; H, 1.07; N, 4.93.
Found: C, 20.96; H, 1.13; N, 4.85%.
2-Bromo-3-substituted pyridines 17a–b
4-Bromo-a-phenyl-3-pyridinemethanol (21) and 3-bromo-
a-phenyl-4-pyridinemethanol (22). Procedure B, starting
from 20 (2.4 g, 10 mmol), using benzaldehyde as an
electrophile, was used to give (CH2Cl2) 21 and 22 in 63
and 34% yield, respectively. Compound (21): mp 150ЊC,
Procedure B was used, starting from 16 (2.4 g, 10 mmol).
2-Bromo-a-phenyl-3-pyridinemethanol (17a). Using
benzaldehyde as an electrophile gave 92% (CH2Cl2) of
17a: mp 124–125ЊC (Lit. 2g mp 125ЊC); 1H NMR
(CDCl3) d 3.50 (s, 1H, OH), 6.12 (s, 1H, CHOH), 7.3 (m,
6H, H5, Ph), 7.90 (d, 1H, H4), 8.19 (d, 1H, H6), J4,6ˆ1.8,
J5,6ˆ4.6, J4,5ˆ7.7 Hz; 13C NMR (CDCl3) d 73.6 (CHOH),
123.0 (C5), 127.0 (C2,6), 127.9 (C4), 128.4 (C3,5), 136.9 (C4),
140.1 (C1), 141.3 (C2), 141.9 (C3), 148.7 (C6); IR (KBr) n
3183, 3036, 2909, 1566, 1493, 1449, 1414, 1400, 1330,
1257, 1213, 1194, 1086, 1032, 840, 796, 758, 742,
693 cmϪ1. Anal. Calcd for C12H10BrNO (264.12): C,
54.57; H, 3.82; N, 5.30. Found: C, 54.51; H, 3.68; N,
5.15%.
1
dec; H NMR (DMSO-d6) d 5.99 (s, 1H, CHOH), 6.30 (s,
1H, OH), 7.3 (m, 5H, Ph), 7.63 (d, 1H, H5), 8.29 (d, 1H, H6),
8.81 (s, 1H, H2), J5,6ˆ5.3 Hz; 13C NMR (DMSO-d6) d 72.3
(CHOH), 127.2 (C2,6), 127.7 (C4), 127.8 (C5), 128.6 (C3,5),
132.3 (C4), 139.9 (C1), 143.1 (C3), 149.4 (C6), 150.0 (C2); IR
(KBr) n 3096, 2855, 1576, 1466, 1406, 1226, 1062, 1047,
750, 701 cmϪ1. Anal. Calcd for C12H10BrNO (264.12): C,
54.57; H, 3.82; N, 5.30. Found: C, 54.80; H, 3.89; N, 5.08%.
Compound (22):18 mp 130–132ЊC; 1H NMR (CDCl3) d 3.70
(s, 1H, OH), 6.11 (s, 1H, CHOH), 7.3 (m, 5H, Ph), 7.73 (d,
1H, H5), 8.38 (d, 1H, H6), 8.50 (s, 1H, H2), J5,6ˆ5.3 Hz; 13
C

´
F. Trecourt et al. / Tetrahedron 56 (2000) 1349–1360
1359
11. (a) Mallet, M. J. Organomet. Chem. 1991, 406, 49–56. (b) den
Hertog, H. J.; Hoogzand, C. Recl. Trav. Chim. Pays-Bas 1957, 76,
261–266. (c) Talik, Z.; Talik, T. Roczniki Chem. 1962, 36,
417–423; Chem. Abstr. 1963, 58, 5627.
12. (a) Newkome, G. R.; Roper, J. M. J. Org. Chem. 1979, 44,
502–505. (b) Shaikh, A. A.; Thaker, K. A. J. Indian Chem. Soc.
1968, 45, 378–380. (c) Jones, G.; Mouat, D. J.; Tonkinson, D. J.
J. Chem. Soc., Perkin Trans. 1 1985, 2719–2723. (d) Moody, C. J.;
Morfitt, C. N. Synthesis 1998, 1039–1042. (e) Gros, P.; Fort, Y.;
NMR (CDCl3) d 73.8 (CHOH), 120.6 (C3), 122.6 (C5),
127.2 (C2,6), 128.2 (C4), 128.6 (C3,5), 140.6 (C1), 148.2
(C6), 151.4 (C4), 151.5 (C2); IR (KBr) n 3139, 3083,
2838, 1587, 1456, 1402, 1311, 1057, 1024, 765, 733, 700,
659 cmϪ1. Anal. Calcd for C12H10BrNO (264.12): C, 54.57;
H, 3.82; N, 5.30. Found: C, 54.35; H, 3.79; N, 5.09%.
Acknowledgements
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Caubere, P. J. Chem. Soc., Perkin Trans. 1 1997, 3597–3600. (f)
´ ´
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We thank Frederic Simian, Jerome Mazajczyk, Olivier
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Marcq and Gerald Chaumaz for their contribution to this
study.
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