Grignard and cerium reagents of pyrimidine derivatives

Article abstract of DOI:10.1055/s-1999-3404

5-(Pyrimidinyl)magnesium and cerium chlorides were prepared via the halogen-metal exchange of 5-bromopyrimidine with ethylmagnesium chloride and a sequential treatment of butyl-lithium and cerium(III) chloride, respectively. In a similar way, 5-[2,4-di(te

Full text of DOI:10.1055/s-1999-3404

PAPER
495
Grignard and Cerium Reagents of Pyrimidine Derivatives
Akihiko Shimura,a Atsuya Momotake,b Hideo Togo,a Masataka Yokoyama*a,b
a Department of Chemistry, Faculty of Science, Chiba University, Yayoi-cho 1Ð33, Inage-ku, Chiba City 263Ð8522, Japan
b Graduate School of Science and Technology, Chiba University, Yayoi-cho 1Ð33, Inage-ku, Chiba City 263Ð8522, Japan
Fax: +81(43)2902874; E-mail: yokoyama@scichem.c.chiba-u.ac.jp
Received 6 April 1998; revised 12 October 1998
hydropyrimidine (6) in 20% and 70% yields based on 1,
respectively. Therefore, the preparation of 4 may require
an improved procedure for its synthetic application
(Scheme 1).
Abstract: 5-(Pyrimidinyl)magnesium and cerium chlorides were
prepared via the halogenÐmetal exchange of 5-bromopyrimidine
with ethylmagnesium chloride and a sequential treatment of butyl-
lithium and cerium(III) chloride, respectively. In a similar way, 5-
[2,4-di(tert-butoxy)pyrimidinyl]magnesium and cerium chlorides
were prepared from the reaction of 5-bromo-2,4-di(tert-butoxy)-
pyrimidine with ethylmagnesium chloride and butylcerium chlo-
ride, respectively.
Key words: Grignard reagents, cerium reagents, pyrimidines,
uracil, pseudouridine
Since the pseudouridine was found from active transfer
RNA as a first C-nucleoside which appeared to play an
important role in the protein synthesis, many C-nucleo-
sides were isolated from nature and exhibited anticancer
and/or antiviral activity.1 As part of our program for syn-
thesis and evaluation of a new type of DNA and RNA sub-
units,2 we intended to prepare the stable metal salts of
pyrimidine and uracil for the coupling synthesis of pyrim-
idine C-nucleosides because their lithium salts3 were sta-
ble only under Ð70¡C and decomposed instantly at room
temperature. Herein we report the first preparations and
their utilization for the magnesium and cerium salts of
pyrimidine and uracil.
Scheme 1
The reagent 3 was allowed to react with typical carbonyl
compounds 11 to give the corresponding alcohols 12 in
moderate yields. For the readily enolizable ketones (11b
and 11c), the reagent 3 increased the yields remarkably
over those of lithium reagent 2 (Scheme 3 and Table 1).
To our knowledge, the magnesium salts of aromatic het-
erocycles have been prepared by the following methods:
(1) oxidative addition of active magnesium to the halo-
heterocycles (thiophene and benzothiophene2m); (2) halo-
genÐmetal exchange with alkyl or aryl Grignard reagent
(thiophene,4 pyridine,4,5 indole6 and imidazole7); and (3)
hydrogenÐmetal exchange with magnesium amide
(indole8). From some preliminary experiments, we chose
the halogenÐmetal exchange method for the metallation of
pyrimidine and uracil.
Secondly, 5-[2,4-di(tert-butoxy)pyrimidinyl]magnesium
chloride (8) was prepared from 5-bromo-2,4-di(tert-but-
oxy)pyrimidine (7) via the halogenÐmetal exchange with
ethylmagnesium chloride. Among the several alkyl
Grignard reagents examined such as butylmagnesium
chloride, bromide, iodide etc., ethylmagnesium chloride
was the best reagent.
Interestingly, 5-[2,4-di(tert-butoxy)pyrimidinyl]cerium
chloride (10) was prepared from a one-step halogenÐmet-
al exchange of 7 with butylcerium chloride and could not
The cerium salt of 2-methylthiopyrimidine has been pre-
pared from the reaction of 5-bromo-2-methylthiopyrimi-
dine with butyllithium followed by treatment with
cerium(III) chloride.9 First, we could also obtain the ceri-
um salt of pyrimidine 3 cleanly from 5-bromopyrimidine
(1) according to the above method. The one-step halogenÐ
metal exchange of 1 with butylcerium chloride did not
take place successfully, resulting in the formation of a nu-
cleophilic addition product, 5-bromo-4-butyl-3,4-dihy-
dropyrimidine (5) (80% yield). On the other hand, 5-
pyrimidinylmagnesium chloride (4) was prepared from
the reaction of 1 with ethylmagnesium chloride. However,
the reaction of benzaldehyde with 4 gave the correspond-
ing alcohol 12a and a byproduct, 5-bromo-4-ethyl-3,4-di-
Table 1 Addition of Reagent 2 or 3 to 11
Carbonyl compds 11
12 Yield (%)
Reagent 2
R1
R2
Reagent 3
11a
11b
11c
Ph
Bn
Ph
H
Bn
Me
67
15
42
80
61
71
Synthesis 1999, No. 3, 495Ð499 ISSN 0039-7881 © Thieme Stuttgart á New York

496
A. Shimura et al.
PAPER
be prepared via lithium salt 9 as in the Undheim method
(Scheme 2).
Table 2 Addition of Reagent 8, 9 or 10 to 11
Carbonyl compds 11 13 Yield (%)
Conversion
Yield (%)
13 → 14
R1
R2
Re-
Re-
Re-
agent 8 agent 9 agent 10
11a
11b
11c
11d
11e
11f
Ph
Bn Bn
Ph
Pr
Ph
H
80
90
36
56
70
50
62
62
62
68
72
70
65
96
80
88
82
85
79
8a
Me
H
Ph
30a
53
41
37
Ð(CH2)5Ð
a Reagent 8 (3 equiv.) was used.
[[a]D +17.5 (c = 0.25, MeOH)] increased to 48% and 26%
respectively in the case of the reagent 8. Reagent 10 gave
altro-16 and allo-16 in 29% and 29% yields, respectively
(Scheme 4). Therefore, use of Grignard reagent 8 showed
better results than that of 9.
Scheme 2
In further studies, we applied the lithium reagent 9 to our
preparative method for b-pseudouridine.2f In the first step
of the reaction, the addition of 9 to 5-O-(tert-butyldimeth-
ylsilyl)-2,3-O-isopropylidene-D-ribofuranose (17) gave
5-O-(tert-butyldimethylsilyl)-1-[5-[2',4'-di(tert-butoxy)-
pyrimidinyl]-2,3-O-isopropylidene-D-ribitol (18) in 35%
yield, while use of reagent 8 increased the yield to 56%
(Scheme 5).
In conclusion, the first Grignard and cerium reagents of
pyrimidine and uracil were prepared. The Grignard re-
Scheme 3
Some aldehydes and ketones were treated with 8, 9, and
10 to give the corresponding alcohols 13, which were then
deprotected with conc. HCl to give 14 in good yield. For
the enolizable ketones such as 11b, 11c, and 11f, use of
cerium reagent 10 gave a good result (Scheme 3 and Table
2). The spectroscopic data of compounds 5Ð18 are sum-
marized in Table 3.
Furthermore, we examined the application of reagents 8
and 10 to the C-nucleoside synthesis. In the synthesis of
pseudouridine as a typical C-nucleoside, Shapiro and
Chambers have reported the isolation of b-form in only
2% yield from the reaction of 2,3,5-tri-O-benzoyl-D-ribo-
furanosyl chloride with 2,4-dimethoxypyrimidin-5-yllith-
ium.10 Later, Moffatt and co-workers have presented its
effective preparative method for b-pseudouridine from
the reaction of 2,4:3,5-di-O-benzylidenealdehyde-D-ri-
bose 15 with 2,4-di-tert-butoxypyrimidin-5-yllithium 9
(37% yield as altro-16 from which the desired b-pseudo-
uridine was obtained in 56% yield).11
Then, the addition of reagents 8 or 10 to 15 was examined.
The results were summarized as follows: the yields of
altro-16 [[a]D Ð67.2 (c = 0.25, MeOH)] and allo-16
Scheme 4
Synthesis 1999, No. 3, 495Ð499 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Grignard and Cerium Reagents of Pyrimidine Derivatives
497
used effectively in the reaction of the readily enolizable
aldehydes and ketones. In our laboratory, their use is on-
going for the synthesis of new type of DNA and RNA sub-
units.
Microanalyses were performed with a Perkin-Elmer 2400 elemental
analyser at the Chemical Analysis Center of Chiba University. IR
spectra were recorded on a Hitachi 215 specrometer. Mass spectra
were obtained on Hitachi M-60 and JEOL JMS-HX 110 mass spec-
trometers. 1H NMR spectra were measured [CDCl3 as solvent (un-
less specified otherwise), using TMS as internal reference] with
JEOL-GSX-400 spectrometer. Wakogel C-200 and 300 were used
for TLC and Wakogel B-5F for preparative TLC (PTLC).
5-(Pyrimidinyl)lithium (2)
Schema 5
To a mixture of 5-bromopyridine (320 mg, 2 mmol) and THF
(30 mL) was added 1.67 M BuLi in hexane (1.23 mL, 2 mmol) at
Ð100 ¡C and the mixture was stirred at the same temperature for 1 h
to give 2.
agent of uracil 8 can be handled without decomposition at
room temperature and increases the yields for the prepara-
tion of pseudouridine. The cerium reagents 3 and 10 are
Table 3 IR and MS Data of Compounds 5 Ð 18 Prepared
Producta
Molecular
Formula
IR (Neat)
HRMS (FAB/NBA) m/z
n (cmÐ1)
calc.
found
5
C8H13BrN2
(217.1)
3060, 2960, 1680, 1560
217.0341, 219.0321
(M + H)+
217.0320, 219.0341
(M + H)+
6
C6H9BrN2
(189.1)
3170, 2960, 1630, 1550
189.0028, 191.0008
189.0003, 190.9977
(M + H)+
(M + H)+
12a
12b
12c
13a
13b
13c
13d
13e
13f
14a
14b
14c
14d
14e
14f
18
C11H10N2O
(186.2)
C19H18N2O
(290.4)
C12H12N2O
(200.2)
C19H26N2O3
(330.4)
C27H34N2O3
(434.6)
C20H28N2O3
(344.5)
C16H28N2O3
(296.4)
C25H30N2O3
(406.5)
C18H30N2O3
(322.5)
C11H10N2O3
(218.2)
C19H18N2O3
(322.4)
C12H12N2O3
(232.2)
C8H12N2O3
(184.2)
C17H14N2O3
(294.3)
C10H14N2O3
(210.2)
C26H48N2O7Si
(528.8)
3260, 1570, 1410, 860
187.0871
187.0878
(M + H)+
(M + H)+
3300, 3030, 1560, 1420
291.1497
291.1483
(M + H)+
(M + H)+
3260, 2980, 1560, 1410
201.1028
201.1006
(M + H)+
(M + H)+
3230, 2980, 1560, 1420, 1150, 840
3530, 3450, 2980, 1590, 1420, 1170, 1050, 900
3560, 3430, 2980, 1590, 1420, 1170, 1080, 900
3360, 2960, 1560, 1420, 1160, 800
3420, 2980, 1670, 1570, 1160, 850
3250, 2930, 1650, 1420, 1160, 850
3420, 3220, 1720, 1680, 1450, 1100
3430, 3230, 1720, 1680, 1420, 1030
3450, 3220, 1730, 1650, 1440, 770
3440, 3210, 1740, 1680, 1440, 970
3240, 3300, 1700, 1680, 1470, 1070
3240, 3210, 1730, 1670, 1450, 850
2980, 2940, 1600, 1560, 1440, 940
331.2022
331.2005
(M + H)+
(M + H)+
435.2648
435.2638
(M + H)+
(M + H)+
345.2178
345.2183
(M + H)+
(M + H)+
297.2178
297.2160
(M + H)+
(M + H)+
407.2335
407.2308
(M + H)+
(M + H)+
323.2335
323.2311
(M + H)+
(M + H)+
201.0664
201.0666
(M Ð H2O + H)+
305.1290
(M Ð H2O + H)+
305.1301
(M Ð H2O + H)+
215.0821
(M Ð H2O + H)+
215.0813
(M Ð H2O + H)+
167.0821
(M Ð H2O + H)+
167.0827
(M Ð H2O + H)+
277.0977
(M Ð H2O + H)+
277.0986
(M Ð H2O + H)+
193.0977
(M Ð H2O + H)+
193.0983
(M Ð H2O + H)+
529.3309
(M Ð H2O + H)+
529.3326
(M + H)+
(M + H)+
a Satisfactory microanalyses obtained: C ± 0.35, H ± 0.30, N ± 0.20.
Synthesis 1999, No. 3, 495Ð499 ISSN 0039-7881 © Thieme Stuttgart · New York

498
A. Shimura et al.
PAPER
Table 4 1H NMR Data of Compounds 5Ð18 Prepared
Product 1H NMRa
δ, J (Hz)
5
6
0.92Ð1.87 (10 H, m, 6-H, butyl), 4.61 (1 H, br, 1-H), 6.61 (1 H, s, 4-H), 8.43 (1 H, br, 2-H)
1.01 (3 H, t, 2'-H, J = 7.5), 1.56Ð1.63 (1 H, m, 1'-Ha), 1.80Ð1.87 (1 H, m, 1'-Hb), 3.62 (1 H, br, 1-H), 4.39 (1 H, t, 6-H, J = 4.6),
6.52 (1 H, s, 4-H), 7.08 (1 H, s, 2-H)
12a
12b
3.73 (1 H, br, OH), 5.85 (1 H, s, 1'-H), 7.30Ð7.40 (5 H, m, Ph), 8.68 (2 H, s, 4, 6-H), 9.00 (1 H, s, 2-H)
2.18 (1 H, br, OH), 3.19 (2 H, d, CH2, J = 13.5), 3.27 (2 H, d, CH2, J = 13.8), 6.97Ð7.00 (4 H, m, Ph), 7.19Ð7.22 (6 H, m, Ph),
8.59 (2 H, s, 4, 6-H), 9.04 (1 H, s, 2-H)
12c
13a
13b
1.99 (3 H, s, 2'-H), 3.17 (1 H, br, OH), 7.28Ð7.43 (5 H, m, Ph), 8.74 (2 H, s, 4, 6-H), 9.01 (1 H, s, 2-H)
1.48 (9 H, s, O-t-Bu), 1.59 (9 H, s, O-t-Bu), 2.82 (1 H, br, OH), 5.74 (1 H, s, 1'-H), 7.26Ð7.38 (5 H, m, Ph), 8.15 (1 H, s, 6-H)
1.58 (9 H, s, O-t-Bu), 1.77 (9 H, s, O-t-Bu), 2.32 (1 H, br, OH), 3.05 (2 H, d, CH2, J = 13.4), 3.50 (2 H, d, CH2, J = 13.4), 7.01Ð
7.20 (10 H, m, Ph), 7.79 (1 H, s, 6-H)
13c
13d
1.30 (9 H, s, O-t-Bu), 1.61 (9 H, br, O-t-Bu), 1.79 (3 H, d, Me, J = 1.0), 3.91 (1 H, br d, OH, J = 1.0), 7.21Ð7.30 (5 H, m, Ph),
8.34 (1 H, s, 6-H)
0.95 (3 H, t, 4'-H, J = 7.4), 1.35Ð1.79 (4 H, 2'-H, 3'-H), 1.61 (9 H, s, O-t-Bu), 1.64 (9 H, s, O-t-Bu), 2.43 (1 H, m, 1'-H), 4.62 (1 H,
br, OH), 8.13 (1 H, s, 6-H)
13e
13f
14a
14b
14c
14d
14e
14f
18
1.56 (9 H, s, O-t-Bu), 1.66 (9 H, s, O-t-Bu), 4.80 (1 H, br, OH), 7.25Ð7.35 (10 H, m, Ph), 7.87 (1 H, s, 6-H)
1.58Ð1.94 (10 H, m, cyclohexyl), 1.60 (9 H, s, O-t-Bu), 1.67 (9 H, s, O-t-Bu), 3.33 (1 H, s, OH), 8.17 (1 H, s, 6-H)
5.12 (1 H, s, OH), 7.14 (1 H, d, 6-H, J = 1.0), 7.18Ð7.26 (5 H, m, Ph)
3.60Ð3.70 (4 H, m, CH2), 7.00Ð7.50 (11 H, m, 6-H, Ph)
5.47 (3 H, m, Me), 7.21Ð7.26 (6 H, m, 6-H, Ph)
0.80Ð2.10 (9 H, m, 1', 2', 3' and 4'-H), 7.29 (1 H, s, 6-H)
7.05 (1 H, s, 6-H), 7.16Ð7.39 (10 H, m, Ph)
1.51Ð1.65 (10 H, m, cyclohexyl), 7.11 (1 H, s, 6-H)
0.10 (6 H, s, TBDMS Si-Me), 0.92 (9 H, s, TBDMS Si-t-Bu), 1.33 (3 H, s, isopropylidene Me), 1.60 (3 H, s, isopropylidene Me),
1.60 (9 H, s, O-t-Bu), 1.61 (9 H, s, O-t-Bu), 2.75 (1 H, br, 4'-OH), 2.98 (1 H, br, 1'-OH), 3.72 (1 H, dd, 5'-Ha, Jgem = 10.0, J4',5'a
=
5.2), 3.86 (1 H, dd, 5'-Hb, Jgem = 10.0, J4',5'b = 3.0), 4.10Ð4.20 (2 H, m, 3'-H, 4'-H), 4.34 (1 H, dd, 2'-H, J = 6.1, J = 1.6), 5.25 (1
H, br, 1'-H), 8.27 (1 H, s, 6-H)
(another isomer): 0.12 (6 H, s, TBDMS Si-Me), 0.93 (9 H, s, TBDMS Si-t-Bu), 1.30 (3 H, s, isopropylidene Me), 1.34 (3 H, iso-
propylidene Me), 1.61 (9 H, s, O-t-Bu), 1.63 (9 H, s, O-t-Bu), 3.70Ð3.76 (2 H, m, 5'-Ha, Hb), 3.93 (1 H, m, 4'-H), 4.17 (1 H, dd,
3'-H, J3',4' = 9.8, J2',3' = 5.5), 4.45 (1 H, dd, 2'-H, J1',2'= 9.5, J2',3' = 5.5), 4.96 (1 H, d, 1'-H, J1',2' = 9.5), 8.23 (1 H, 6-H)
a Solvent for 1H NMR; for 5 Ð 13 and 18: CDCl3/TMS; for 14: CD3OD.
5-(Pyrimidinyl)cerium Chloride (3)
5-(Pyrimidinyl)magnesium Chloride (4)
This reagent was prepared according to the literature.9 A mixture of
anhyd CeCl3 which was obtained by stirring CeCl3•7H2O (745 mg,
2 mmol) at 140¡C in vacuo for 3 h and anhyd THF (4 mL) was
stirred at r.t. for 2 h. Meanwhile, to THF (30 mL) containing 5-bro-
mopyrimidine (1) (320 mg, 2 mmol) was added 1.63 M BuLi in
hexane (1.23 mL, 2 mmol) and the mixture was then stirred for 1 h
under Ð100 ¡C. To the resulting solution was added the ceriumÐ
THF solution obtained above and the mixture was then stirred for
1 h at Ð100 ¡C to give 3.
To a mixture of 1 (320 mg, 2 mmol) and THF (30 mL) was added
dropwise 2 M ethylmagnesium chloride in THF (1 mL, 2 mmol) at
Ð100 ¡C. The resulting mixture was stirred for 1 h at the same tem-
perature to give 4, which was used in the same way as mentioned
above to give 12a and 6 in 20% and 70% yields based on 1, respec-
tively. The concentration of 4 could not be increased above 0.014 M
which was determined by D2O quenching.
5-[2,4-Di(tert-butoxy)pyrimidinyl]magnesium Chloride (8)
A 2 M THF solution of ethylmagnesium chloride (0.5 mL, 1 mmol)
was added to a THF solution (4 mL) of 7 (1.2 g, 4 mmol) under
stirring and the mixture further stirred for 1.5 h at r.t. under Ar to
give 8.
5-[1-Hydroxy-1-(phenyl)methyl]pyrimidine (12a);
Typical Procedure
A THF solution (1 mL) containing benzaldehyde (216 mg, 2 mmol)
was dropped into the cerium reagent 3 obtained above (2.2 mmol).
The resulting mixture was stirred at Ð100 ¡C for 3 h and then at r.t.
overnight. The mixture was quenched with 0.1 M HCl (20 mL) and
extracted with EtOAc. The extract was dried (Na2SO4) and evapo-
rated to give a yellow oil, which was purified by pTLC on silica gel
(eluent: hexane / EtOAc = 1) to give 12a in 80% yield. The addition
of the lithium reagent 2 to carbonyl compounds was also carried out
in the same way as the cerium reagent 3.
5-[2,4-Di(tert-butoxy)pyrimidinyl]lithium (9)
To a mixture of 7 (303 mg, 1 mmol) and THF (1 mL) was added
dropwise 1.63 M BuLi hexane solution (0.62 mL, 1 mmol) at Ð78¡C
and the mixture was stirred at the same temperature for 15 min to
give 9.
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PAPER
Grignard and Cerium Reagents of Pyrimidine Derivatives
499
5-[2,4-Di(tert-butoxy)pyrimidinyl]cerium chloride (10)
(c) Togo, H.; Ishigami S.; Yokoyama, M. Chem. Lett. 1992,
1673.
(d) Togo, H.; Aoki, M.; Kuramochi T.; Yokoyama, M.
J. Chem. Soc., Perkin Trans. 1,1993, 2417.
(e) Yokoyama, M.; Tanabe, T.; Toyoshima A.; Togo, H.
Synthesis 1993, 517.
A mixture of anhyd CeCl3 (1 mmol) and anhyd THF (2 mL) was
stirred at r.t. for 2 h. To the resulting slurry solution was added drop-
wise 1.63 M BuLi in hexane (0.62 mL, 1 mmol) at Ð78¡C. After
stirring for additional 30 min, the THF solution containing 7
(606 mg, 2 mmol) was added dropwise to the resulting solution and
the mixture was gently warmed to Ð20¡C for 2 h to give 10.
(f) Yokoyama, M.; Toyoshima, A.; Akiba T.; Togo, H. Chem.
Lett. 1994, 265.
(g) Ishigami, S.; Togo H.; Yokoyama, M. J. Chem. Soc., Per-
kin Trans. 1 1994, 2407.
5-[1-Hydroxy-1-(phenyl)methyl]uracil (14a)
To the magnesium reagent 8 (1.2 mmol) obtained above was added
the THF (1 mL) solution containing benzaldehyde (108 mg,
1 mmol). After stirring overnight, the mixture was quenched with
0.1 M HCl (10 ml) and extracted with EtOAc (3 × 20 mL). The ex-
tract was dried (Na2SO4) and evaporated to give a yellow oil, which
was then purified by pTLC on silica gel (eluent: hexane/EtOAc = 3/
1) to give 13a in 80% yield. Next, a mixture of 13a obtained above,
MeOH (2 mL), and conc. HCl (0.3 mL) was stirred for 5 min under
heating at 60¡C. The resulting solution was evaporated to give a
residue which was then dried by the azeotropic method using anhyd
MeOH. Purification was performed by a HPLC (ODS column) us-
ing MeOH to give 14a in 96% yield.
(h) Togo, H.; Ishigami, S.; Fujii, M.; Ikuma T.; Yokoyama, M.
J. Chem. Soc., Perkin Trans. 1 1994, 2931.
(i) Yokoyama, M.; Akiba T.; Togo, H. Synthesis 1995, 638.
(j) Yokoyama, M.; Nomura, M.; Tanabe T.; Togo, H. Hete-
roatom Chem. 1995, 6, 189.
(k) Yokoyama, M.; Akiba, T.; Ochiai, Y.; Momotake A.; To-
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Queguiner, G.; Marsais, F.; Snieckus V.; Epstajn, J. Adv.
Heterocycl. Chem. 1991, 52, 187.
The addition of the lithium reagent 9 and the cerium reagent 10 to
carbonyl compounds was also carried out at Ð78 ¡C in the same way
as mentioned above. In the preparation of 16 and 18, Grignard re-
agent 8, lithium reagent 9, and cerium reagent 10 were also used in
the same way as described in the preparation of 13a.
(4) Paradies H. H.; Gšrbing, M. Angew. Chem., Int. Ed. Engl.
1969, 8, 279.
(5) Furukawa, N.; Shibutani T.; Fujihara, H. Tetrahedron Lett.
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(6) Kondo, Y.; Yoshida, A.; Sato S.; Sakamoto, T. Heterocycles
Acknowledgement
1996, 42, 105.
This work was supported by a Grant-in-Aid No. 07554085 for Sci-
entiÞc Research from the Ministry of Education, Science and Cul-
ture, Japan and Found for Researching Assistant of Chiba
University (A. M).
Ref. 2m.
(7) Kalish, R.; Broger, E.; Field, G. F.; Steppe T. V.; Sternbach,
L. H. J. Heterocycl. Chem. 1975, 12, 49.
Iddon B.; Ngochindo, R. I. Heterocycles 1994, 38, 2487.
(8) Kondo, Y.; Yoshida, A.; Sakamoto, T. J. Chem. Soc., Perkin
Trans. 1 1996, 2331.
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