The tellurium-lithium exchange reaction: Selective functionalization of electron-deficient heteroaromatics

Article abstract of DOI:10.1016/S0040-4020(01)00089-8

Electron-deficient heteroaromatic tellurides, which was obtained from the corresponding haloheteroaromatics, reacted selectively with n-butyllithium to give the lithio derivatives.

Full text of DOI:10.1016/S0040-4020(01)00089-8

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 2133±2138
The tellurium±lithium exchange reaction: selective
functionalization of electron-de®cient heteroaromatics
Osamu Sugimoto, Muneyoshi Sudo and Ken-ichi Tanjip
Laboratory of Organic Chemistry, School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Received 18 December 2000; accepted 15 January 2001
AbstractÐElectron-de®cient heteroaromatic tellurides, which was obtained from the corresponding haloheteroaromatics, reacted selec-
tively with n-butyllithium to give the lithio derivatives. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
Recently, lithiation via a tellurium±lithium exchange reac-
tion has been reported.4±6 As the rate of the tellurium±
lithium exchange reaction is much faster than that of the
halogen±lithium exchange reaction, the former reaction is
expected to be useful for the lithiation of electron-de®cient
heteroaromatics. Lithiation of electron-de®cient heteroaro-
matics, using the lithium±tellurium exchange reaction, has
not been studied systematically except for the lithiation of a
pyridine derivative.7 Hence, investigations were performed
aimed at establishing the feasibility of introducing an
electrophile into easily accessible electron-de®cient hetero-
aromatics. As a study of the lithiation of 4-chloro-1-phenyl-
1H-pyrazolo[3,4-d]pyrimidine has previously been reported
by us,8 we applied similar methods to the lithiation of some
electron-de®cient haloheteroaromatics in this work.
A number of studies on the lithiation of heteroaromatics
have been reported in review form,1,2 however, data on
the lithiation of electron-de®cient heteroaromatics is sparse,
and there remains a wide unexplored domain. Alkyl-
lithiums, which are often used as lithiating reagents, possess
not only high basicity but also high nucleophilicity. This
dual nature often results in side reactions when using alkyl-
lithiums. Electron-excessive heteroaromatics are relatively
stable to nucleophiles, so they can be lithiated using alkyl-
lithium to give the lithio compound without any side reac-
tions. By contrast, because electron-de®cient heteroaromatics
are generally reactive to nucleophiles and because the
halogeno group acts as a good leaving group, treatment of
electron-de®cient haloheteroaromatics with alkyllithium
proceeds with some side reactions. Hence, there are few
reports on the selective lithiation of electron-de®cient
heteroaromatics. For example, it has been reported that 7-
iodo-3-phenyl-3H-1,2,3-triazolo[4,5-d]pyrimidine is lithiated
at the 7-position,3 but this reaction requires a temperature of
21008C, and gives the corresponding products in low yield.
Similarly, the reaction of 4-iodo-1-phenyl-1H-pyrazolo[3,4-
d]pyrimidine with n-butyllithium in THF at 2788C gave
multispots in thin layer chromatography.
2. Results and discussion
Reaction of 4-chloro-1-phenyl-1H-pyrazolo[3,4-d]pyrimi-
dine (1) with lithium n-butanetellurolate, obtained from
the reaction of tellurium and n-butyllithium, proceeded
smoothly at rt to give n-butyl 1-phenyl-1H-pyrazolo[3,4-
d]pyrimidin-4-yl telluride (2) in 90% yield. Subsequently,
2 was converted into the product 4 in 52% yield using
t
Scheme 1. Reagents and conditions: (i) nBuLi (1.1 equiv.)/2 788C; (ii) BuCHvO (5.0 equiv.)/2 788C to rt; (iii) H3O1/rt.
Keywords: lithiation; tellurium and compounds; heteroaromatics.
Corresponding author. Tel.: 181-54-264-5542; fax: 181-54-264-5099; e-mail: tanji@smail.u-shizuoka-ken.ac.jp
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)00089-8

2134
O. Sugimoto et al. / Tetrahedron 57 (2001) 2133±2138
Table 1. Reagents and conditions: (i) RTeLi (1.1 equiv.)/THF/rt; (ii) RLI/2788C/time; (iii) electrophile (5.0 equiv.)/2 788C to rt; (iv) H3O1/rt
Entry
Lithiation condition
RLi
Electrophile
±E
Yield (%)
Product
Time (min)
5
6
1
2
3
4
5
6
7
8
9
nBuLi (1.1 equiv.)
nBuLi (1.1 equiv.)
nBuLi (3.0 equiv.)
MeLi (1.1 equiv.)
PhLi (1.1 equiv.)
nBuLi (1.1 equiv.)
nBuLi (1.1 equiv.)
nBuLi (1.1 equiv.)
nBuLi (1.1 equiv.)
10
90
10
10
10
10
10
10
10
tBuCHvO
tBuCHvO
tBuCHvO
tBuCHvO
tBuCHvO
PhCHvO
Ph2CvO
±CH(OH)tBu
±CH(OH)tBu
±CH(OH)tBu
±CH(OH)tBu
±CH(OH)tBu
±CH(OH)Ph
±C(OH)Ph2
±C(OH)Me2
±CMe(OH)CHvCH2
74 (4)
50 (4)
43 (4)
48 (4)
16 (4)
61 (7)
82 (8)
68 (9)
48 (10)
14
Me2CvO
MeCOCHvCH2
3
23
n-butyllithium and pivalaldehyde at 2788C (Scheme 1).
The high rate of the tellurium±lithium exchange reaction
and the low ability of the n-butyltelluro group as a leaving
group seems to be the reason for the ease of lithiation of 2.
Thus, our method using the tellurium±lithium exchange
reaction even enables the conversion of the chloro
compound, which is not usually active in the halogen±
lithium exchange reaction, into the lithio adduct.
treatment of 2, generated in situ from 1, with an excess of
n-butyllithium gives the product 5, which is derived from
the nucleophilic attack of n-butyllithium at the 6-position of
the 4-lithio derivative 3 (entry 3). Using methyllithium or
phenyllithium instead of n-butyllithium, we found that the
nature of the alkyllithium affects the yield of the product 4.
The introduction of some electrophiles at the 4-position in
1-phenyl-1H-pyrazolo[3,4-d]pyrimidine was accomplished
in good to fair yields under the best conditions we examined
(entries 6±9). When ketones having a-hydrogens were used
in this reaction, the protonated compound 6 was obtained
(entry 8,9).
As it was found that the telluride 2 was obtained in excellent
yield, the one-pot lithiation without intermdiate isolation of
the telluride 2 was then carried out (Table 1). The conditions
shown in entry 1 of the table gave the product 4 in good
yield. When the lithiating time was extended to 90 min, the
yield of the product 4 showed a slight decline. Hence it
appears that, even at a reaction temperature of 2788C, the
4-lithio derivative 3 is unstable. It should be noted that
Next, lithiation of some electron-de®cient heteroaromatics
shown in Table 2 was carried out. Although the introduction
of an electrophile was accomplished when 2-bromoquino-
line (11), 1-bromoisoquinoline (12), 6-chloro-1,4-diphenyl-
n
Table 2. Reagents and conditions: (i) nBuTeLi (1.1 equiv.)/THF; (ii) BuLi (1.1 equiv.)/2 788C; (iii) pivalaldehyde (5.0 equiv.)/2 788C to rt; (iv) H3O1/rt
Entry
Substrate
Yield (%)
Het±CH(OH)tBu
Het±Het
1
2
3
4
5
6
7
2-bromoquinoline (11)
1-bromoisoquinoline (12)
6-chloro-1,4-diphenyl-1H-pyrazolo[3,4-d]pyrimidine (13)
4-chloro-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine (1)
2-chloro-4-phenylquinazoline (14)
2-chloroquinoxaline (15)
75 (17)
36 (18)
52 (19)
74 (4)
63 (20)
36 (21)
94 (22)
4-chloroquinazoline (16)

O. Sugimoto et al. / Tetrahedron 57 (2001) 2133±2138
2135
Table 3.
Entry
Substrate
Yield (%)
1
2
23 (R2ˆMe, R6ˆCl)
24 (R2ˆCl, R6ˆH)
37 (25: R2ˆMe, R6ˆH), 29 (26: R2ˆCH(OH)tBu)
34 (27: R2ˆR6ˆH)
1H-pyrazolo[3,4-d]pyrimidine (13), 4-chloro-1-phenyl-
1H-pyrazolo[3,4-d]pyrimidine (1) or 2-chloro-4-phenyl-
quinazoli-ne (14) was used, dimerization occurred when
2-chloroquinoxaline (15) or 4-chloroquina-zoline (16)
acted as substrate. It can be estimated that the extent of
dimerization depends on the reactivities of the telluride as
an electrophile and the lithio derivative as a nucleophile.
As the 4-position of quinazoline or the 2-position of quinoxa-
line is highly reactive9 with nucleophiles, such as carbanions,
amines or alkoxides, dimerization occurred when 15 or 16 was
used as a substrate. The 2-position of quinazoline has a similar
reactivity to that of the 2-position of quinoxaline; however,
interestingly dimerization does not occur. We surmise that the
2-carbanion of quinazoline is stabilized by the electron with-
drawing effect of the two ring nitrogens.
1. Since the rate of tellurium±lithium exchange reaction is
so fast, many electron-de®cient heteroaromatic tellurides
react selectively with 1 equiv. of n-butyllithium to give
the corresponding lithio derivatives.
2. When the tellurium-substituted position at heterocycles
has a high reactivity towards nucleophiles, the lithio
derivative reacts with the unreacted telluride to give the
corresponding dimer. The kind of reaction pattern
depends on the position of tellurium-substitution in the
heterocycle. For example, 2-quinazolinyl tellurides gives
2-lithioquinazolines selectively, while 4-quinazolinyl
tellurides gives the 4,40-dimer.
3. The presence of an acidic proton (e.g. the 8-position of
9H-purines) causes relocation of the carbanion.
We postulate that same scheme might be applied to many
heterocycles as yet not researched by us.
Lithiation of 9-phenyl-9H-purine derivatives (23,24) took
place with 8-lithiation to give the 8- (25,27) and 6,8- (26)
substituted products (Table 3). A similar relocation of the
carbanion was reported by Leonard.10
4. Experimental
4.1. General
Lithiation at the 8-position could occur by two main routes.
One would involve hydrogen abstraction at the 8-position of
the 6-carbanion, formed via the tellurium±lithium exchange
reaction, by another 6-carbanion then, the resulting 6,8-
dilithio derivative may abstract hydrogen at the 8-position
from the 6-protonated derivative. Another route would
involve the direct lithiation at the 8-position of the 6-carb-
anion by n-butyllithium (Scheme 2).
1
Melting points were not corrected. H NMR spectra were
measured with HITACHI R-90H spectrometer using TMS
as an internal standard.
4.1.1. Synthesis of n-butyl 1-phenyl-1H-pyrazolo[3,4-
d]pyrimidin-4-yl telluride (2). In a three-necked round-
bottomed ¯ask, a suspension of 281 mg (2.20 mmol) of
tellurium in 30 ml of THF was treated dropwise with
1.58 ml (1.39 M, 2.20 mmol) of n-butyllithium while stir-
ring at rt. As the n-butyllithium was added, the tellurium
dissolved and the reaction mixture turned dark. The solution
became colorless near the equivalence point. After stirring
the reaction mixture for 10 min, a solution of 461 mg
(2.00 mmol) of 4-chloro-1-phenyl-1H-pyrazolo[3,4-d]pyri-
3. Conclusion
On examining the lithiation of electron-de®cient heteroaro-
matics using the tellurium±lithium exchange reaction, we
observed the following (these reactions can be divided
broadly into three patterns):
Scheme 2.

2136
O. Sugimoto et al. / Tetrahedron 57 (2001) 2133±2138
Entry
Alkyllithium (equiv.)
Lithiation time (min)
Product in mg (yield in %)
4
5
1
2
3
4
5
nBuLi (1.1)
10
90
10
10
10
418 (74)
281 (50)
237 (43)
273 (48)
90 (16)
nBuLi (1.1)
nBuLi (3.0)
MeLi (1.1)
PhLi (1.1)
97 (14)
midine (1) in 12 ml of THF was added and stirred for
10 min. 50 ml of water was added and neutralized with
1N HCl. The mixture was extracted with ethyl acetate and
dried over Na2SO4. The solvent was removed by rotary
evaporation, and residual crude product puri®ed with SiO2
chromatography (eluted with hexane±ethyl acetate (10:1))
to give 684 mg (90%) of n-butyl 1-phenyl-1H-pyrazo-
then warmed to rt, and 50 ml of water was added, and
neutralized with 1N HCl. The mixture was extracted with
ethyl acetate and dried over Na2SO4. The solvent was
removed by a rotary evaporator, and the residual crude
product was puri®ed with SiO2 chromatography.
4.1.4. 2,2-Dimethyl-1-(6-n-butyl-1-phenyl-1H-pyrazolo-
[3,4-d]pyrimidin-4-yl)-1-propanol (5). Pale-yellow oil.
1
lo[3,4-d]pyrimidin-4-yl telluride (2). Pale-green solids. H
t
1H NMR (CDCl3); ppm: 0.77±1.15 (12H, m, Bu and
NMR (CDCl3); ppm: 0.97 (3H, t, Jˆ6.9 Hz, ±CH2CH2
CH2CH3), 1.13±1.67 (2H, m, ±CH2CH2CH2CH3), 1.67±
2.16 (2H, m, ±CH2CH2CH2CH3), 3.43 (2H, t, Jˆ7.3 Hz, ±
CH2CH2CH2CH3), 7.25±7.67 (3H, m, phenyl-H), 8.08 (1H,
s, C3±H), 8.10±8.31 (2H, m, phenyl-H), 8.77 (1H, s, C6±H);
Anal. calcd for C15H16N4Te: C, 47.42; H, 4.24; N, 14.75.
Found: C, 47.53; H, 4.03; N, 14.47.
CH2CH2CH2CH3), 1.15±1.64 (2H, m, CH2CH2CH2CH3),
1.64±2.08 (2H, m, CH2CH2CH2CH3), 3.09 (2H, t, Jˆ
7.5 Hz, CH2CH2CH2CH3), 4.05 (1H, d, Jˆ7.3 Hz, ±OH),
4.73 (1H, d, Jˆ7.3 Hz, ±CH±), 7.27±7.68 (3H, m, phenyl-
H), 8.14±8.41 (2H, m, phenyl-H), 8.23 (1H, s, C3±H). Anal.
calcd for C20H26N4O: C, 70.98; H, 7.74; N, 16.55. Found: C,
71.01; H, 7.74; N, 16.52.
4.1.2. Lithiation of 2. In a three-necked round-bottomed
¯ask, a solution of 760 mg (2.00 mmol) of 2 in 30 ml of
THF was treated with 1.58 ml (1.39 M, 2.20 mmol) of
n-butyllithium in one portion while being stirred at an inter-
ior temperature of 2788C. The mixture was stirred for
10 min then 861 mg (10.0 mmol) of pivalaldehyde was
added. The reaction mixture was then warmed to rt and
50 ml of water was added, and neutralized with 1N HCl.
The mixture was extracted with ethyl acetate and dried over
Na2SO4. The solvent was removed by a rotary evaporator,
and the residual crude product was puri®ed with SiO2
chromatography (eluted with hexane±ethyl acetate (2:1))
to give 294 mg (52%) of 2,2-dimethyl-1-(1-phenyl-1H-
pyrazolo[3,4-d]pyrimidin-4-yl)-1-propanol (4). Pale-yellow
prisms (recryst. from hexane±ethyl acetate). Mp 125±
4.1.5. Lithiation of some haloheteroarenes: general
procedure. A solution of starting material in THF was
added to the solution of n-butanetellurolate in THF at con-
dition. The mixture was cooled to 2788C, treated with
n-butyllithium in one portion. The mixture was stirred for
10 min then, electrophile was added. The reaction mixture
was then warmed to rt, water was added, and neutralized
with 1N HCl. The mixture was extracted with ethyl acetate
and dried over Na2SO4. The solvent was removed by a
rotary evaporator, and the residual crude product was puri-
®ed with SiO2 chromatography.
4.1.6. Phenyl(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-
yl)methanol (7). Lithium n-butanetellurolate (2.20 mmol),
1 461 mg (2.00 mmol), n-butyllithium (2.20 mmol) and
benzaldehyde 1061 mg (10.0 mmol) were used in this reac-
tion to give 370 mg (yield: 61%) of the compound11 accord-
ing to the protocol described in general procedure (condition:
rt/10 min). White solids. Mp 103±1048C (lit. 107±1108C). 1H
NMR (CDCl3); ppm: 4.78 (1H, d, Jˆ3.8 Hz, ±OH), 6.08 (1H,
d, Jˆ3.8 Hz, ±CH±), 7.26±7.68 (8H, m, phenyl-H), 8.01 (1H,
s, C3±H), 8.03±8.30 (2H, m, phenyl-H), 9.07 (1H, s, C6±H).
1
1268C. H NMR (CDCl3); ppm: 1.04 (9H, s, C(CH3)3),
3.70 (1H, d, Jˆ6.8 Hz, ±OH), 4.78 (1H, d, Jˆ6.8 Hz, ±
CH±), 7.26±7.70 (3H, m, phenyl-H), 8.00±8.35 (2H, m,
phenyl-H), 8.36 (1H, s, C3±H), 9.05 (1H, s, C6±H); Anal.
calcd for C16H18N4O: C, 68.06; H, 6.43; N, 19.84. Found: C,
67.87; H, 6.38; N, 20.02.
4.1.3. Lithiation of 2 generated in situ from 1. In a three-
necked round-bottomed ¯ask, a suspension of tellurium
(2.20 mmol) in THF (30 ml) was treated dropwise with
alkyllithium (2.20 mmol) while stirring at rt. As alkyl-
lithium was added, tellurium was dissolved and the reaction
mixture turned dark. This change of color proved the
equation of the amount of alkyllithium. This change of
color con®rmed the supposed stoichiometry. After stirring
the reaction mixture for10 min, a solution of 1 (2.00 mmol)
in THF (12 ml) was added and stirred at an appropriate
temperature. The mixture was cooled to 2788C then treated
with alkyllithium (molar: shown in Table 4) in one portion
while being stirred at an interior temperature of 2788C. The
mixture was stirred for the time shown below then, electro-
phile (10.0 mmol) was added. The reaction mixture was
4.1.7. Diphenyl(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-
yl)methanol (8). Lithium n-butanetellurolate (2.20 mmol), 1
461 mg (2.00 mmol), n-butyllithium (2.20 mmol) and benzo-
phenone 1822 mg (10.0 mmol) were used in this reaction to
give 624 mg (yield: 82%) of the compound according to the
protocol described in general procedure (condition: rt/
10 min). White needles (recryst. from hexane±ethyl acetate).
Mp 219±2218C. 1H NMR (DMSO-d6); ppm: 7.15±7.80 (13H,
m, aromatic-H), 8.06±8.30 (2H, m, aromatic-H), 8.53 (1H, s,
C3±H), 9.05 (1H, s, C6±H). Anal. calcd for C24H18N4O: C,
76.17; H, 4.79; N, 14.81. Found: C, 76.23; H, 4.82; N, 14.64.
4.1.8. 2-(1-Phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2-

O. Sugimoto et al. / Tetrahedron 57 (2001) 2133±2138
2137
propanol (9)Lithium n-butanetellurolate (2.20 mmol), 1
461 mg (2.00 mmol), n-butyllithium (2.20 mmol) and ace-
tone 580 mg (10.0 mmol) were used in this reaction to give
344 mg (yield: 68%) of the compound and 12 mg (yield:
3%) of 612 according to the protocol described in general
procedure (condition: rt/10 min). Yellow prisms (recryst.
aromatic-H), 8.50 (1H, d, Jˆ5.7 Hz, aromatic-H); Anal.
calcd for C14H17NO: C, 78.10; H, 7.96; N, 6.51. Found: C,
78.12; H, 7.83; N, 6.54.
4.1.13. 2,2-Dimethyl-1-(1,4-diphenyl-1H-pyrazolo[3,4-d]-
pyrimidin-6-yl)-1-propanol (19). Lithium n-butanetelluro-
late (2.20 mmol), 6-chloro-1,4-diphenyl-1H-pyrazolo[3,4-
d]pyrimidine (13) 614 mg (2.00 mmol), n-butyllithium
(2.20 mmol) and pivalaldehyde 861 mg (10.0 mmol) were
used in this reaction to give 370 mg (yield: 52%) of the
compound according to the protocol described in general
procedure (condition: rt/10 min). Pale-yellow needles
1
from hexane±ethyl acetate). Mp 758C. H NMR (CDCl3);
ppm: 1.76 (6H, s, (CH3)2), 4.33 (1H, s, ±OH), 7.32±7.77
(3H, m, phenyl-H), 8.12±8.40 (2H, m, phenyl-H), 8.47 (1H,
s, C3±H), 9.03 (1H, s, C6±H). Anal. calcd for C14H14N4O: C,
66.13; H, 5.55; N, 22.03. Found: C, 66.12; H, 5.38; N, 21.86.
1
4.1.9. 1-Phenyl-1H-pyrazolo[3,4-d]pyrimidine (6). Lithium
n-butanetellurolate (2.20 mmol), 1 461 mg (2.00 mmol),
(recryst. from hexane±ethyl acetate). Mp 1588C. H NMR
t
(CDCl3); ppm: 1.07 (9H, s, Bu), 4.29 (1H, d, Jˆ7.7 Hz, ±
n-butyllithium
(2.20 mmol)
and
acetone
580 mg
OH), 4.68 (1H, d, Jˆ7.7 Hz, ±CH±), 7.26±7.75 (6H, m,
phenyl-H), 8.09±8.37 (4H, m, phenyl-H), 8.52 (1H, s, C3±
H). Anal. calcd for C22H22N4O: C, 73.72; H, 6.19; N, 15.63.
Found: C, 73.84; H, 6.36; N, 15.48.
(10.0 mmol) were used in this reaction to give 12 mg (yield:
3%) of the compound12 and 344 mg (yield: 68%) of 9 accord-
ing to the protocol described in general procedure (condition:
1
rt/10 min). Pale-yellow solids. Mp 808C (lit. 79±818C). H
NMR (CDCl3); ppm: 7.30±7.70 (3H, m, phenyl-H), 8.11±
8.40 (2H, m, phenyl-H), 8.32 (1H, s, C3±H), 9.13 (1H, s,
C6±H), 9.27 (1H, s, C4±H).
4.1.14.
2,2-Dimethyl-1-(4-phenylquinazolin-2-yl)-1-
propanol (20). Lithium n-butanetellurolate (2.20 mmol),
2-chloro-4-phenylquinazoline (14) 481 mg (2.00 mmol),
n-butyllithium (2.20 mmol), and pivalaldehyde 861 mg
(10.0 mmol) were used in this reaction to give 366 mg
(yield: 63%) of the compound according to the protocol
described in general procedure (condition: rt/10 min).
White needles (recryst. from hexane±ethyl acetate). Mp
120±1218C. H NMR (CDCl3); ppm: 1.05 (9H, s, Bu),
4.42 (1H, d, Jˆ7.7 Hz, ±OH), 4.72 (1H, d, Jˆ7.7 Hz, ±
CH±), 7.40±8.24 (9H, m, aromatic-H); Anal. calcd for
C19H20N2O: C, 78.05; H, 6.89; N, 9.58. Found: C, 78.00;
H, 6.90; N, 9.66.
4.1.10. 2-(1-Phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-
3-buten-2-ol (10). Lithium n-butanetellurolate (2.20
mmol), 1 461 mg (2.00 mmol), n-butyllithium (2.20
mmol) and 3-buten-2-one 700 mg (10.0 mmol) were used
in this reaction to give 255 mg (yield: 48%) of the
compound and 90 mg (yield: 23%) of 6 according to the
protocol described in general procedure (condition: rt/
10 min). White powder (recryst. from hexane±ethyl ace-
1
t
1
tate). Mp 65±668C. H NMR (CDCl3); ppm: 1.84 (3H, s,
CH3), 4.63 (1H, s, ±OH), 5.28 (1H, dd, Jˆ10.4, 0.9 Hz,
alkene-H), 5.56 (1H, dd, Jˆ17.1, 0.9 Hz, alkene-H), 6.33
(1H, dd, Jˆ17.1, 10.4 Hz, alkene-H), 7.31±7.71 (3H, m,
phenyl-H), 8.12±8.33 (2H, m, phenyl-H), 8.44 (1H, s, C3±
H), 9.03 (1H, s, C6±H); Anal. calcd for C15H14N4O: C,
67.65; H, 5.30; N, 21.04. Found: C, 67.51; H, 5.30; N, 20.78.
4.1.15. 2,20-Biquinoxalinyl (21). Lithium n-butanetelluro-
late (2.20 mmol), 2-chloroquinoxaline (15) 329 mg
(2.00 mmol), n-butyllithium (2.20 mmol) and pivalalde-
hyde 861 mg (10.0 mmol) were used in this reaction to
give 95 mg (yield: 36%) of the compound13 according to
the protocol described in general procedure (condition: rt/
1
4.1.11. 2,2-Dimethyl-1-(2-quinolinyl)-1-propanol (17).
Lithium n-butanetellurolate (2.20 mmol), 2-bromoquinoline
(11) 416 mg (2.00 mmol), n-butyllithium (2.20 mmol) and
pivalaldehyde 861 mg (10.0 mmol) were used in this reac-
tion to give 323 mg (yield: 75%) of the compound according
to the protocol described in general procedure (condition:
re¯ux/43 h). Pale-yellow plates (recryst. from hexane±ethyl
acetate). Mp 73±758C. 1H NMR (CDCl3); ppm: 0.98 (9H, s,
tBu), 4.20±5.10 (1H, br, ±OH), 4.53 (1H, brs, ±CH±),
7.14±7.95 (4H, m, aromatic-H), 8.09 (2H, d, Jˆ8.4 Hz,
aromatic-H); Anal. calcd for C14H17NO: C, 78.10; H,
7.96; N, 6.51. Found: C, 78.00; H, 7.99; N, 6.58.
10 min). Dark-red solids. Mp 2728C (lit. 2748C). H NMR
(CDCl3); ppm: 7.76±8.06 (4H, m, aromatic-H), 8.11±8.42
0
(4H, m, aromatic-H), 10.13 (2H, s, C3 and C3 ±H).
4.1.16. 4,40-Biquinazolinyl (22). Lithium n-butanetelluro-
late (2.20 mmol), 4-chloroquinazoline (16) 329 mg
(2.00 mmol), n-butyllithium (2.20 mmol) and pivalalde-
hyde 861 mg (10.0 mmol) were used in this reaction to
give 240 mg (yield: 94%) of the compound14 according to
the protocol described in general procedure (condition: rt/
10 min). White solids. Mp 210±2128C (lit. 208±2098C). 1H
0
NMR (CDCl3); ppm: 7.50±7.83 (2H0, m, C6 and C6 ±H),
0
7.83±8.17 (4H, m, C5, C7, C5 and C7 ±H), 8.17±8.42 (2H,
0
0
4.1.12. 2,2-Dimethyl-1-(1-isoquinolinyl)-1-propanol (18).
Lithium n-butanetellurolate (2.20 mmol), 1-bromoisoquino-
line (12) 320 mg (1.54 mmol), n-butyllithium (1.69 mmol)
and pivalaldehyde 662 mg (7.69 mmol) were used in this
reaction to give 118 mg (yield: 36%) of the compound
and 75 mg (yield: 38%) of isoquinoline according to the
protocol described in general procedure (condition: re¯ux/
24 h). White needles (recryst. from hexane). Mp 106±
m, C8 and C8 ±H), 9.54 (2H, s, C2 and C2 ±H).
4.1.17. 2,2-Dimethyl-1-(2-methyl-9-phenyl-9H-purin-8-
yl)-1-propanol
(25).
Lithium
n-butanetellurolate
(1.10 mmol), 6-chloro-2-methyl-9-phenyl-9H-purine (23)
245 mg (1.00 mmol), n-butyllithium (1.10 mmol) and
pivalaldehyde 431 mg (5.00 mmol) were used in this
reaction to give 110 mg (yield: 37%) of the compound
and 111 mg (yield: 29%) of 26 according to the protocol
described in general procedure (condition: rt/30 min). Pale-
yellow powder (recryst. from hexane±ethyl acetate). Mp
1
t
1078C. H NMR (CDCl3); ppm: 0.95 (9H, s, Bu), 4. 50
(1H, d, Jˆ8.8 Hz, ±OH), 5.26 (1H, d, Jˆ8.8 Hz, ±CH±),
7.42±7.97 (4H, m, aromatic-H), 8.06±8.31 (1H, m,

2138
O. Sugimoto et al. / Tetrahedron 57 (2001) 2133±2138
1868C. 1H NMR (CDCl3); ppm: 0.90 (9H, s, tBu), 2.75 (3H,
s, CH3), 3.09 (1H, d, Jˆ9.7 Hz, ±OH), 4.56 (1H, d,
Jˆ9.7 Hz, ±CH±), 7.28±7.75 (5H, m, phenyl-H), 9.06
(1H, s, C6±H). Anal. calcd for C17H20N4O: C, 68.89; H,
6.80; N, 18.90. Found: C, 69.12; H, 6.71; N, 18.74.
C16H18N4O: C, 68.06; H, 6.43; N, 19.84. Found: C, 68.08;
H, 6.35; N, 19.61.
References
1. Queguiner, G.; Marsais, F.; Snieckus, V.; Epsztajn, J. Adv.
Heterocycl. Chem. 1991, 52, 187±304.
4.1.18. 6,8-Bis(1-hydroxy-2,2-dimethylpropyl)-2-methyl-
9-phenyl-9H-purine (26). Lithium n-butanetellurolate
(1.10 mmol), 6-chloro-2-methyl-9-phenyl-9H-purine (23)
245 mg (1.00 mmol), n-butyllithium (1.10 mmol) and
pivalaldehyde 431 mg (5.00 mmol) were used in this reac-
tion to give 111 mg (yield: 29%) of the compound and
110 mg (yield: 37%) of 25 according to the protocol
described in general procedure (condition: rt/30 min).
Pale-yellow prisms (recryst. from hexane). Mp 176±
2. Rewcastle, G. W.; Katritzky, A. R. Adv. Heterocycl. Chem.
1993, 56, 155±302.
3. Tanji, K.; Kato, H.; Higashino, T. Chem. Pharm. Bull. 1991,
39, 2793±2796.
4. Hiiro, T.; Morita, Y.; Inoue, T.; Kambe, N.; Ogawa, A.;
Ryu, I.; Sonoda, N. J. Am. Chem. Soc. 1990, 112, 455±457.
5. Hiiro, T.; Kambe, N.; Ogawa, A.; Miyoshi, N.; Murai, S.;
Sonoda, N. Angew. Chem., Int. Ed. Engl. 1987, 26, 1187±
1188.
1
t
1798C. H NMR (CDCl3); ppm: 0.87 (9H, s, Bu), 1.03
t
(9H, s, Bu), 2.72 (3H, s, CH3), 2.90 (1H, dd, Jˆ9.8,
6. Hiiro, T.; Mogami, T.; Kambe, N.; Fujiwara, S.; Sonoda, N.
Synth. Commun. 1990, 20, 703±711.
5.6 Hz, ±OH), 4.30±4.60 (2H, m, ±CH± and ±OH), 4.96
(1H, t, Jˆ8.8 Hz, ±CH±), 7.30±7.67 (5H, m, phenyl-H).
Anal. calcd for C22H30N4O2: C, 69.08; H,7.91; N, 14.65.
Found: C, 69.12; H, 7.85; N, 14.54.
7. Kondo, Y.; Shilai, M.; Uchiyama, M.; Sakamoto, T. J. Chem.
Soc., Perkin Trans. 1 1996, 1781±1782.
8. Sugimoto, O.; Sudo, M.; Tanji, K. Tetrahedron Lett. 1999, 40,
2139±2140.
4.1.19.
2,2-Dimethyl-1-(9-phenyl-9H-purin-8-yl)-1-pro-
9. Chapman, N. B.; Russell-Hill, D. Q. J. Chem. Soc. 1956,
1563±1572.
panol (27). Lithium n-butanetellurolate (2.20 mmol),
2-chloro-9-phenyl-9H-purine (24) 461 mg (2.00 mmol),
n-butyllithium (2.20 mmol) and pivalaldehyde 861 mg
(10.0 mmol) were used in this reaction to give 190 mg
(yield: 34%) of 111 mg (yield: 29%) of the compound
according to the protocol described in general procedure
(condition: rt/2 h). Pale-yellow needles (recryst. from
hexane±ethyl acetate). Mp 1648C. 1H NMR (CDCl3);
10. Leonard, N. J.; Bryant, J. D. J. Org. Chem. 1979, 44, 4612±
4616.
11. Higashino, T.; Goi, M.; Hayashi, E. Chem. Pharm. Bull. 1976,
24, 238±252.
12. Higashino, T.; Iwai, Y.; Hayashi, E. Yakugaku Zasshi 1974,
94, 666±671.
t
13. Maurer, K.; Boettger, B. Chem. Ber. 1938, 71, 2092±2094.
14. Higashino, T. Chem. Pharm. Bull. 1962, 10, 1043±1047.
ppm: 0.92 (9H, s, Bu), 3.08 (1H, d, Jˆ9.7 Hz, ±OH),
4.60 (1H, d, Jˆ9.7 Hz, ±CH), 7.31±7.74 (5H, m, phenyl-
H), 8.95 (1H, s, C2±H), 9.18 (1H, s, C6±H). Anal. calcd for