Preparation of nitrogen-containing π-deficient heteroaromatic Grignard reagents: Oxidative magnesiation of nitrogen-containing π-deficient halogenoheteroaromatics using active magnesium

Article abstract of DOI:10.1021/jo026492a

The oxidative magnesiation of nitrogen-containing π-deficient halogenoheteroaromatics using active magnesium was accomplished. Both magnesiation followed by addition of a carbonyl compound (Grignard reaction) and magnesiation in the presence of a carbonyl compound (Barbier reaction) were carried out to afford the corresponding product. Especially, the latter method enabled fused halogenodiazines such as 4-chloro-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine or 2-chloroquinoxaline to magnesiate at a mild temperature (-20 to 30 °C).

Full text of DOI:10.1021/jo026492a

tion),6-11 and only one report12 about the oxidative
magnesiation of 3-bromopyridine derivative using a
magnesium metal is known. Recently, study of the
oxidative magnesiation of halogenopyridines using active
magnesium has been reported by us.13 We applied this
method to the oxidative magnesiation of some π-deficient
halogenoheteroaromatics and report the results in this
paper.
P r ep a r a tion of Nitr ogen -Con ta in in g
π-Deficien t Heter oa r om a tic Gr ign a r d
Rea gen ts: Oxid a tive Ma gn esia tion of
Nitr ogen -Con ta in in g π-Deficien t
Ha logen oh eter oa r om a tics Usin g
Active Ma gn esiu m
Osamu Sugimoto,* Shigeru Yamada, and
Ken-ichi Tanji*
Table 1 shows the results of oxidative magnesiation of
halogenopyridines followed by addition of some carbonyl
compounds (Grignard reaction). Oxidative magnesiation
of 2-chloro-, 2-bromo-, and 2-iodopyridine took place at
-20 to 30 °C followed by addition of propionaldehyde to
give 1-(2-pyridinyl)-1-propanol (entries 1-6). Analogous
results were obtained when benzaldehyde (entry 7) or
benzophenone (entry 8) was used as an electrophile. It
should be noted that even chloropyridine was magnesi-
ated, whereas magnesiation of a chloropyridine derivative
hardly proceeded using isopropylmagnesium halide (chlo-
rine-magnesium exchange).6-11 Oxidative magnesiation
of 2-halogenopyridine followed by addition of 2-phenyl-
propionaldehyde (entries 9 and 10), pivalaldehyde (en-
tries 11 and 12), and 3-pentanone (entry 13) gave
pyridine (observed by TLC) and a small amount of the
product. These results can be explained as follows:
2-Pyridinylmagnesium halide is prepared smoothly by
the reaction of 2-halogenopyridine and Mg*. When a
bulky aldehyde (2-phenylpropionaldehyde and pivalal-
dehyde) or a ketone (3-pentanone) is used as an electro-
phile, however, 2-pyridinylmagnesium halide cannot
react with the electrophile and reacts with water at
posttreatment to afford pyridine.
Table 2 describes the results of oxidative magnesiation
of halogenopyridines in the presence of carbonyl com-
pounds (Barbier reaction). To our surprise, the relation-
ship of carbonyl compounds to yields of the products in
Table 2 were apparently different from that of Table 1.
The magnesiation of 2-iodopyridine in the presence of
propionaldehyde afforded no product with the recovery
of the substrate (entries 1 and 2). The corresponding
product was obtained only in 17% yield when benzalde-
hyde was used in this reaction (entry 3). On the contrary,
the oxidative magnesiation of 2-iodopyridine in the
presence of pivalaldehyde or 3-pentanone at 0-35 °C
gave the product in 50-67% yields (entries 6-8 and 13),
whereas the same reaction under the condition of Table
1 did not proceed. The oxidative magnesiation was
inhibited when excess aldehyde compared to Mg* was
used (entry 9). When 2-chloro- or 2-bromopyridine was
Laboratory of Organic Chemistry, School of Food and
Nutritional Sciences, University of Shizuoka, 52-1 Yada,
Shizuoka 422-8526, J apan
osamu@smail.u-shizuoka-ken.ac.jp
Received September 30, 2002
Abstr a ct: The oxidative magnesiation of nitrogen-contain-
ing π-deficient halogenoheteroaromatics using active mag-
nesium was accomplished. Both magnesiation followed by
addition of a carbonyl compound (Grignard reaction) and
magnesiation in the presence of a carbonyl compound
(Barbier reaction) were carried out to afford the correspond-
ing product. Especially, the latter method enabled fused
halogenodiazines such as 4-chloro-1-phenyl-1H-pyrazolo[3,4-
d]pyrimidine or 2-chloroquinoxaline to magnesiate at a mild
temperature (-20 to 30 °C).
Since many natural products or medicinal drugs are
made up of nitrogen-containing π-deficient heteroaro-
matics, studies of these compounds are of much interest
to many chemists. It is well-known that π-deficient
heteroaromatics react with nucleophiles to give the
corresponding substituted product. On the other hand,
it is usually difficult to introduce an electrophilic sub-
stituent into π-deficient heteroaromatics mainly for two
reasons. One is that π-deficient heteroaromatics hardly
undergo electrophilic substitution (e.g., Friedel-Crafts
acylation), and the other is that metalation of π-deficient
heteroaromatics has been reported insufficiently. For
example, preparation of lithiopyridine is accomplished by
the reaction of halogenopyridine with alkyllithium1,2 or
lithium naphthalenide3,4 or by the reaction of telluropy-
ridine with alkyllithium,5 but these reactions require a
low temperature such as -78 °C. On the contrary,
magnesiopyridine is stable enough compared to lithiopy-
ridine to be prepared at room temperature.6 However,
magnesiopyridine is usually prepared by the reaction of
bromo- or iodopyridine, which is less available and
expensive compared to chloropyridine, with alkylmag-
nesium halide (the halogen-magnesium exchange reac-
(7) Berillon, L.; Lepretre, A.; Turck, A.; Ple, N.; Queguiner, G.;
Cahiez, G.; Knochel, P. Synlett 1998, 1359-1360.
(8) Trecourt, F.; Breton, G.; Bonnet, V.; Mongin, F.; Marsais, F.;
Queguiner, G. Tetrahedron Lett. 1999, 40, 4339-4342.
(9) Abarbri, M.; Dehmel, F.; Knochel, P. Tetrahedron Lett. 1999, 40,
7449-7453.
(10) Abarbri, M.; Thibonnet, J .; Berillon, L.; Dehmel, F.; Rottlander,
M.; Knochel, P. J . Org. Chem. 2000, 65, 4618-4634.
(11) Trecourt, F.; Breton, G.; Bonnet, V.; Mongin, F.; Marsais, F.;
Queguiner, G. Tetrahedron 2000, 56, 1349-1360.
(12) Bell, A. S.; Roberts, D. A.; Ruddock, K. S. Synthesis 1987, 843-
844.
(1) Peterson, M. A.; Mitchell, J . R. J . Org. Chem. 1997, 62, 8237-
8239.
(2) Hannon, M. J .; Mayers, P. C.; Taylor, P. C. Tetrahedrion Lett.
1998, 39, 8509-8512.
(3) Kondo, Y.; Murata, N.; Sakamoto, T. Heterocycles 1994, 37,
1467-1468.
(4) Gomez, I.; Alonso, E.; Ramon, D. J .; Yus, M. Tetrahedron 2000,
56, 4043-4052.
(5) Kondo, Y.; Shilai, M.; Uchiyama, M.; Sakamoto, T. J . Chem. Soc.,
Perkin Trans. 1 1996, 1781-1782.
(6) Furukawa, N.; Shibutani, T.; Fujihara, H. Tetrahedron Lett.
1987, 28, 5845-5848.
(13) Sugimoto, O.; Yamada, S.; Tanji, K. Tetrahedron Lett. 2002,
43, 3355-3357.
10.1021/jo026492a CCC: $25.00 © 2003 American Chemical Society
Published on Web 02/11/2003
2054
J . Org. Chem. 2003, 68, 2054-2057

TABLE 1. Oxid a tive Ma gn esia tion of 2-Ha logen op yr id in e F ollow ed by Ad d ition of Som e Ca r bon yl Com p ou n d s
amount (equiv)
entry
X
Mg*
electrophile
electrophile
E
condition 1
condition 2
yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
Cl
Cl
Br
Br
I
4
4
4
4
4
3
3
3
4
2
3
4
4
4
4
4
4
4
5
5
5
4
2
5
3
4
EtCHdO
EtCHdO
EtCHdO
EtCHdO
EtCHdO
EtCHdO
PhCHdO
Ph2CdO
PhMeCHCHdO
PhMeCHCHdO
tBuCHdO
tBuCHdO
Et2CdO
2-CH(OH)Et
2-CH(OH)Et
2-CH(OH)Et
2-CH(OH)Et
2-CH(OH)Et
2-CH(OH)Et
2-CH(OH)Ph
30 °C, 15 min
30 °C, 3 h
30 °C, 15 min
30 °C, 2 h
-20 °C, 30 min
20 °C, 5 min
20 °C, 5 min
0 °C, 5 min
30 °C, 1 h
25-30 °C, 17 h
25-30 °C, 17 h
25-30 °C, 19 h
25-30 °C, 14 h
warmed to 25 °C
25 °C, 1 h
25 °C, 1 h
25 °C, 1 h
25∼30 °C, 17 h
25 °C, 20 min
25 °C, 30 min
25 °C, 18 h
56
54
52
60
46
40
65
56
20a
24a
6a
I
Cl
Cl
Cl
I
Br
I
2-C(OH)Ph2
2-CH(OH)CHMePh
2-CH(OH)CHMePh
2-CH(OH)tBu
2-CH(OH)tBu
2-C(OH)Et2
20 °C, 30 min
20 °C, 4 h
20 °C, 4 h
14a
0a
Br
30 °C, 1 h
25-30 °C, 19 h
a
Generation of pyridine was observed by TLC.
TABLE 2. Oxid a tive Ma gn esia tion of 2-Ha logen op yr id in es u n d er Ba r bier Con d ition s
amount (equiv)
entry
X
Mg*
electrophile
electrophile
E
condition
yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
I
I
I
I
I
I
I
I
4
4
4
4
4
4
4
4
4
4
3
3
4
3
3
3
3
3
3
3
3
5
3
2
2
3
EtCHdO
EtCHdO
PhCHdO
Ph2CdO
PhMeCHCHdO
tBuCHdO
tBuCHdO
tBuCHdO
tBuCHdO
tBuCHdO
tBuCHdO
tBuCHdO
Et2CdO
2-CH(OH)Et
2-CH(OH)Et
2-CH(OH)Ph
2-C(OH)Ph2
2-CH(OH)CHMePh
2-CH(OH)tBu
2-CH(OH)tBu
2-CH(OH)tBu
2-CH(OH)tBu
2-CH(OH)tBu
2-CH(OH)tBu
2-CH(OH)tBu
2-C(OH)Et2
-78 °C, 10 min to rt
20 °C, 30 min
20 °C, 30 min
20 °C, 30 min
20 °C, 30 min
0 °C, 30 min
20 °C, 30 min
35 °C, 30 min
20 °C, 30 min
20 °C, 30 min
25-30 °C, 24 h
reflux, 2 h
0a
0a
17
71
35
67
65
55
42
tra
0a
I
Br
Cl
Cl
I
21a
50
20 °C, 30 min
a
The substrate was observed by TLC.
F IGURE 1. Magnesiation of 2-halogenopyridines shown in Tables 1 and 2. Comparison of the yield of products. (1) EtCHdO; (2)
t
PhCHdO; (3) Ph2CdO; (4) PhMeCHCHdO; (5) BuCHdO; (6) Et2CdO.
used as a substrate, the magnesiation at 20-30 °C hardly
proceeded, and the reaction under reflux gave the cor-
responding product in a low yield (entries 10-12). These
results would indicate that Mg* and the oxygen atom of
a carbonyl compound make a coordinate state and Mg*
becomes inert.
Figure 1 displays the relationship of carbonyl com-
pounds to yields of the products in Tables 1 and 2. The
results would be based upon two factors: affinity of a
carbonyl compound for Mg* and reactivity of 2-pyridi-
nylmagnesium halide. Grignard reaction using a bulky
aldehyde (e.g., pivalaldehyde) or a ketone (e.g., 3-pen-
tanone) hardly proceeded because these carbonyl com-
pounds had insufficient reactivities with the Grignard
reagent (RMgX), which comes to equilibrium with R2Mg
and MgX2 to be a stable form in THF. On the other hand,
Barbier reaction using these carbonyl compounds pro-
ceeded to afford the corresponding products, because as
J . Org. Chem, Vol. 68, No. 5, 2003 2055

TABLE 3. Oxid a tive Ma gn esia tion of
without extra cooling such as -78 °C (entries 7-12).
Especially, since a method to introduce an electrophilic
substituent to the quinoxaline moiety has not been
established, this Barbier-type magnesiation would be a
useful method. The reaction of 4-chloroquinazoline af-
forded no desired product and gave 4,4′-biquinazolinyl
in 21-45% yields even though under the Barbier condi-
tions (entries 13 and 14). This result may indicate that
4-quinazolinylmagnesium chloride, which was inert to
pivalaldehyde, reacted with the substrate, 4-chloro-
quinazoline. It was found that many fused heteroaro-
matics were more reactive toward oxidative magnesiation
than monocyclic heteroaromatics such as pyridine.
In conclusion, two magnesiating reactions (Grignard
reaction and Barbier reaction) of nitrogen-containing
π-deficient halogenoheteroaromatics have been accom-
plished. Even a chloro compound, which was regarded
as an inert substrate for the metalating reaction, was
magnesiated without requiring low temperature.
Ha logen oh eter oa r om a tics u n d er Ba r bier Con d ition s
yield (%)
Het-CH-
by-
entry substrate
X
condition
20 °C, 30 min
(OH)tBu product
1
2
3
4
5
6
7
8
9
10
11
12
13
14
A
A
B
B
B
B
C
C
C
D
D
D
E
3-I
4-I
73
64
14a
28
59
42
41
43
47
51
51
40
20 °C, 30 min
2-Cl -20 °C, 30 min
2-Cl 20 °C, 30 min
2-Br -20 °C, 30 min
2-Br 20 °C, 30 min
Cl
Cl
Br
Cl
Cl
Cl
Cl
Cl
-20 °C, 30 min
0 °C, 15 min
-20 °C, 30 min to 25 °C
-40 °C, 5 min
-20 °C, 10 min
0 °C, 5 min
Exp er im en ta l Section
All manipulations were carried out under an argon atmo-
sphere. Tetrahydrofuran was distilled from lithium aluminum
hydride and triphenylmethane before use. Halogenopyridines
and 3-bromoquinoline are commercially available. 4-Halogeno-
1-phenyl-1H-pyrazolo[3,4-d]pyrimidines, 2-halogenoquinoxa-
lines, and 4-chloroquinazoline were prepared by the reaction of
the corresponding hydroxy compound with triphenylphosphine
and N-halogenosuccinimide.16,17 Melting points were not cor-
rected.
-70 °C, 10 min
-20 °C, 10 min
0a
0
21b
45b
E
a
b
The substrate was recovered or observed by TLC. 4,4′-
Biquinazolinyl.
soon as Grignard reagent generated, the carbonyl com-
pound reacted immediately with the “active” Grignard
reagent. It was found that propionaldehyde and benzal-
dehyde were not suitable for Barbier reaction. These
results may indicate that nonbulky aldehydes have easy
access to Mg* so that 2-iodopyridine is unable to be
magnesiated.
P r ep a r a tion of Mg*.18,19 Under argon atmosphere, a mixture
of lithium (83.3 mg, 12.0 mmol), naphthalene (1538 mg, 12.0
mmol), magnesium dichloride (571 mg, 6.00 mmol), and tet-
rahydrofuran (30 mL) was stirred at room temperature until
the lithium was completely consumed (2-3 h) to give a gray
suspension of Mg* (about 0.2 M). The amount of these reagents
may be used in proportion to that of the substrate.
Oxid a tive Ma gn esia tion of 2-Ha logen op yr id in es F ol-
low ed by Ad d ition of Ca r bon yl Com p ou n d s (Gr ign a r d
Rea ction ). Gen er a l P r oced u r e of Ta ble 1. To a suspension
of Mg* in tetrahydrofuran, a solution of 2-halogenopyridine in
tetrahydrofuran was added dropwise so as to maintain the given
temperature inside the flask (Condition 1). After the mixture
was stirred for an appropriate time (Condition 1), an electrophile
was added and the mixture was stirred (Condition 2). The
reaction mixture was quenched with aqueous hydrochloric acid
and extracted with ethyl acetate. The organic layer was dried
over sodium sulfate and treated with silica gel chromatography
to give the corresponding product.
Since many nitrogen-containing π-deficient heteroaro-
matics, especially fused diazines as shown in Table 3,
are highly reactive with nucleophiles, metalation of these
compounds requires a low temperature. For example,
7-iodo-3-phenyl-3H-1,2,3-triazolo[4,5-d]pyrimidine is lithi-
ated at the 7-position,14 but this reaction requires -100
°C and gives the corresponding products in low yield.
Moreover, lithiation of quinoxaline or quinazoline using
tellurium-lithium exchange reaction gave the dimer (2,2′-
biquinoxalinyl or 4,4′-biquinazolinyl) even at -78 °C.15
Thus, we applied the Barbier-type magnesiation to some
nitrogen-containing π-deficient halogenoheteroaromatics.
Table 3 shows the oxidative magnesiation of some
halogenoheteroaromatics in the presence of pivalalde-
hyde. 3-Iodopyridine and 4-iodopyridine were smoothly
magnesiated to afford the product in 73% and 64% yields,
respectively (entries 1 and 2). 2-Chloro- or 2-bromoquino-
line reacted with Mg* in the presence of pivalaldehyde
at -20 °C to afford the corresponding product in 14-
59% yields (entries 3-6), whereas 2-chloro- or 2-bro-
mopyridine was hardly magnesiated at 20 °C. The
4-chloro or 4-bromo derivative of 1-phenyl-1H-pyrazolo-
[3,4-d]pyrimidine, 2-chloroquinoxaline was magnesiated
to give the corresponding products in moderate yields
Oxid a tive Ma gn esia tion of Ha logen oh eter oa r om a tics in
th e P r esen ce of Ca r bon yl Com p ou n d s (Ba r bier Rea ction ).
Gen er a l P r oced u r e of Ta bles 2 a n d 3. To a suspension of
Mg* in tetrahydrofuran was added a carbonyl compound at the
temperature shown in Tables 2 and 3. A solution of halogeno-
heteroaromatics in tetrahydrofuran was added dropwise so as
to maintain the given temperature. The mixture was stirred for
the time shown in Tables 2 and 3 and raised to room temper-
ature. The reaction mixture was quenched with aqueous hydro-
chloric acid and extracted with ethyl acetate. The organic layer
was dried over sodium sulfate and treated with silica gel
chromatography to give the corresponding product.
1-(2-P yr id in yl)-1-p r op a n ol20 was purified with silica gel
chromatography (eluted with hexanes-ethyl acetate (2:5)) as
pale yellow oil. 1H NMR (CDCl3) ppm: δ 0.94 (3H, t, J ) 7.3
Hz), 1.31-2.12 (2H, m), 3.00-4.40 (1H, br), 4.68 (1H, t, J ) 5.8
(14) Tanji, K.; Kato, H.; Higashino, T. Chem. Pharm. Bull. 1991,
(16) Sugimoto, O.; Mori, M.; Moriya, K.; Tanji, K. Helv. Chim. Acta
2001, 84, 1112-1118.
(17) Sugimoto, O.; Mori, M.; Tanji, K. Tetrahedron Lett. 1999, 40,
7477-7478.
39, 2793-2796.
(15) Sugimoto, O.; Sudo, M.; Tanji, K. Tetrahedron 2001, 57, 2133-
2138.
2056 J . Org. Chem., Vol. 68, No. 5, 2003

Hz), 7.05-7.35 (2H, m), 7.68 (1H, td, J ) 7.6 Hz, 1.6 Hz), 8.53
(1H, d, J ) 4.8 Hz).
white powder. Mp 89-90 °C (lit. 81-83 °C). 1H NMR (CDCl3)
ppm: δ 0.90 (9H, s), 3.63 (1H, brs), 4.37 (1H, s), 7.19 (1H, dd, J
) 7.9 Hz, 4.8 Hz), 7.67 (1H, dt, J ) 7.9 Hz, 1.8 Hz), 8.25-8.45
(2H, m).
P h en yl(2-p yr id in yl)m eth a n ol21 was purified with silica gel
chromatography (eluted with hexanes-ethyl acetate (1:1)) as
pale yellow solids. Mp 59 °C (lit. 76-78 °C). 1H NMR (CDCl3)
ppm: δ 4.30-6.00 (1H, br), 5.74 (1H, s), 7.03-7.49 (7H, m), 7.61
(1H, td, J ) 7.7 Hz, 1.8 Hz), 8.56 (1H, d, J ) 5.1 Hz).
Dip h en yl(2-p yr id in yl)m eth a n ol22 was purified with silica
gel chromatography (eluted with hexanes-ethyl acetate (10:1))
2,2-Dim et h yl-1-(4-p yr id in yl)-1-p r op a n ol25 was purified
with silica gel chromatography (eluted with ethyl acetate) as a
white powder. Mp 112 °C (lit. 115.5-116.5 °C). 1H NMR (CDCl3)
ppm: δ 0.92 (9H, s), 2.90-3.50 (1H, br), 4.35 (1H, s), 7.22 (2H,
d, J ) 4.6 Hz), 8.42 (2H, d, J ) 4.6 Hz).
1
2,2-Dim eth yl-1-(2-qu in olin yl)-1-p r op a n ol4,26 was purified
with silica gel chromatography (eluted with hexanes-ethyl
acetate (4:1)) as yellow oil. 1H NMR (CDCl3) ppm: δ 0.98 (9H,
s), 4.20-5.10 (1H, br), 4.53 (1H, brs), 7.14-7.95 (4H, m), 8.09
(2H, d, J ) 8.4 Hz).
as white solids. Mp 101 °C (lit. 105 °C). H NMR (CDCl3) ppm:
δ 6.23 (1H, brs), 6.92-7.47 (12H, m), 7.62 (1H, td, J ) 7.7 Hz,
1.4 Hz), 8.56 (1H, dd, J ) 4.8 Hz, 1.4 Hz).
2-P h en yl-1-(2-p yr id in yl)-1-p r op a n ol6 was purified with
silica gel chromatography (eluted with hexanes-ethyl acetate
(2:1)) as white solids. Mp 80-82 °C. 1H NMR (CDCl3) ppm: δ
1.27 (3H, d, J ) 7.0 Hz), 2.60-3.96 (1H, br), 2.86-3.26 (1H, m),
4.80 (1H, d, J ) 5.5 Hz), 6.91 (1H, d, J ) 7.8 Hz), 6.98-7.41
(6H, m), 7.52 (1H, td, J ) 7.8 Hz, 1.3 Hz), 8.51 (1H, dd, J ) 4.8
Hz, 1.3 Hz).
2,2-Dim eth yl-1-(1-p h en yl-1H-p yr a zolo[3,4-d ]p yr im id in -
4-yl)-1-p r op a n ol15,27 was purified with silica gel chromatogra-
phy (eluted with hexanes-ethyl acetate (3:1)) as pale yellow
solids. Mp 115 °C (lit. 125-126 °C). 1H NMR (CDCl3) ppm: δ
1.03 (9H, s), 3.74 (1H, brs), 4.77 (1H, brs), 7.29-7.68 (3H, m),
8.10-8.35 (2H, m), 8.36 (1H, s), 9.04 (1H, s).
2,2-Dim et h yl-1-(2-p yr id in yl)-1-p r op a n ol23 was purified
with silica gel chromatography (eluted with hexanes-ethyl
acetate (2:1)) as pale yellow oil. 1H NMR (CDCl3) ppm: δ 0.92
(9H, s), 4.35 (2H, brs), 7.06-7.34 (2H, m), 7.48-7.77 (1H, m),
8.46-8.66 (1H, m).
2,2-Dim eth yl-1-(2-qu in oxa lin yl)-1-p r op a n ol was purified
with silica gel chromatography (eluted with hexanes-ethyl
acetate (3:1)) as yellow oil. Bp 165 °C /0.9 mmHg. 1H NMR
(CDCl3) ppm: δ 1.00 (9H, s), 4.06 (1H, d, J ) 6.7 Hz), 4.65 (1H,
d, J ) 6.7 Hz), 7.62-7.88 (2H, m), 7.94-8.22 (2H, m), 8.83 (1H,
s). Anal. Calcd for C13H16N2O: C, 72.19; H, 7.46; N, 12.95.
Found: C, 72.21; H, 7.64; N, 12.87.
3-(2-P yr id in yl)-3-p en ta n ol4 was purified with silica gel
chromatography (eluted with hexanes-ethyl acetate (12:1)) as
colorless oil. Bp 122 °C/13 mmHg. 1H NMR (CDCl3) ppm: δ 0.68
(6H, t, J ) 7.4 Hz), 1.82 (2H, q, J ) 7.3 Hz), 1.85 (2H, q, J ) 7.3
Hz), 5.21 (1H, brs), 7.07-7.39 (2H, m), 7.56-7.83 (1H, m), 8.44-
8.61 (1H, m).
4,4′-Biqu in a zolin yl28 was purified with silica gel chroma-
tography (eluted with hexanes-ethyl acetate (1:2)) as pale yellow
solids. 1H NMR (CDCl3) ppm: δ 7.48-7.74 (2H, m), 7.82-8.10
(4H, m), 8.10-8.32 (2H, m), 9.54 (2H, s).
2,2-Dim et h yl-1-(3-p yr id in yl)-1-p r op a n ol24 was purified
with silica gel chromatography (eluted with ethyl acetate) as
J O026492A
(18) Xiong, H.; Rieke, R. D. J . Org. Chem. 1989, 54, 3247-3249.
(19) Sell, M. S.; Xiong, H.; Rieke, R. D. Tetrahedron Lett. 1993, 34,
6007-6010.
(24) Sauter, F.; Stanetty, P.; Sittenthaler, W.; Waditschatka, R.
Monatsh. Chem. 1988, 119, 1427-1438.
(20) Moody, C. J .; Morfitt, C. N. Synthesis 1998, 1039-1042.
(21) Tilford, C. H.; Shelton, R. S.; Van Campen, M. G. J . Am. Chem.
Soc. 1948, 70, 4001-4009.
(25) Traynelis, V. J .; Yamauchi, K.; Kimball, J . P. J . Am. Chem.
Soc. 1974, 96, 7289-7294.
(26) Gros, P.; Fort, Y.; Caubere, P. J . Chem. Soc., Perkin Trans. 1
1997, 3597-3600.
(22) Tschitschibabin, A. E.; Benewolenskaja, S. W. Ber. 1928, 61,
547-555.
(23) Chelucci, G.; Soccolini, F. Tetrahedron: Asymmetry 1992, 3,
1235-1238.
(27) Sugimoto, O.; Sudo, M.; Tanji, K. Tetrahedron Lett. 1999, 40,
2139-2140.
(28) Higashino, T. Chem. Pharm. Bull. 1962, 10, 1043-4047.
J . Org. Chem, Vol. 68, No. 5, 2003 2057