Microwave-assisted synthesis of polysubstituted pyridazines

Article abstract of DOI:10.1055/s-2005-918926

3,4,6-Trisubstituted pyridazines are prepared through a microwave-assisted cyclocondensation of differently substituted 1,4-diketones and hydrazine in the presence of DDQ. The 1,4-diketones can be easily prepared through a functional homologation of comme

Full text of DOI:10.1055/s-2005-918926

LETTER
2743
Microwave-Assisted Synthesis of Polysubstituted Pyridazines
M
icrowave-Assist
i
e
d
Synt
a
hesis of
P
o
c
lysubstitute
o
d Pyridazine
m
s
o Minetto, L. Raffaella Lampariello, Maurizio Taddei*
Dipartimento Farmaco Chimico Tecnologico and Dipartimento di Chimica, Università degli Studi di Siena, Via A. Moro, 53100 Siena, Italy
Fax +39(0577)234333; E-mail: taddei.m@unisi.it
Received 12 July 2005
O
OMe NH2NH2·H2O
O
O
O
Abstract: 3,4,6-Trisubstituted pyridazines are prepared through a
microwave-assisted cyclocondensation of differently substituted
1,4-diketones and hydrazine in the presence of DDQ. The 1,4-di-
ketones can be easily prepared through a functional homologation
of commercially available b-keto esters providing a very rapid entry
to these family of pharmaceutically important compounds.
ref. 6
MW
Ph
OMe
1
2
O
COOMe
Ph
COOMe
Ph
COOMe
COOMe
Ph
Ph
Key words: pyridazines, microwaves, cyclocondensation, combi-
natorial chemistry
N
NH
NH
N
N
N
N
H
6
5
NH2
4
3
ox.
Heterocyclic chemistry is nowadays experiencing a re-
newed interest for the preparation of libraries of drug-like
compounds to be submitted to high throughput biological
screening.1 The presence in many natural products and
drugs makes heterocycles ideal scaffolds for the prepara-
tion of collections of new compounds through elaboration
of functionalities present in the substituents. Pyridazines
show different interesting pharmacological activities and
have inspired several researchers to design new potential
therapeutic agents based on this heterocycle.2 Conse-
quently, syntheses of these compounds have attracted
considerable interest3 especially in the case of synthetic
protocols that allow the generation of a high level of di-
versity.4 Generally, syntheses of polysubstituted py-
ridazines are based on nucleophilic substitution on 3- or 6-
halopyridazines using different Pd-based chemistry or
other organometallic approaches.5 Although very effi-
cient, these methods limit the possibility of introducing
diversity in position 3 or 4.
14
Scheme 1
The reaction of 1,4-diketones and hydrazine has been re-
ported to afford pyridazines directly.10 However, we ob-
served that the products obtained in this reaction were a
mixture of dihydropyridazines 3–5. Although compounds
3–5 could be easily transformed into the corresponding
pyridazines using different oxidizing agents,11 a high-
throughput synthesis required the formation of the py-
ridazine ring in a single step. The keto ester 1 was used as
a model compound and we found that, when the reaction
was carried out in the presence of 5 equivalents of hydra-
zine and 1.5 equivalents of DDQ, pyridazine 14 was ob-
tained in 72% yield.
Table 1 Microwave-Assisted Preparation of Pyridazines
COOMe
Recently, we described a convenient procedure to prepare
polyfunctionalized 1,4-dicarbonyl compounds based on
the functional homologation of b-keto esters with differ-
ent aldehydes in the presence of Et2Zn/CH2I2.6 As similar
compounds have been described as suitable substrates to
prepare pyridazines,7 we explored the possibility of carry-
ing out a microwave-assisted cyclocondensation to pro-
duce a rapid entry to 3,4,6-trisubstituted pyridazines.
NH2NH2·H2O
MW, AcOH, DDQ
O
OMe
R2
R2
O
R1
N
R1
N
O
2, 7–13
14–21
Diketone; R1, R2
2; t-Bu, Ph
Reaction conditions
120 °C, 1.5 min
120 °C, 1.5 min
120 °C, 1.5 min
120 °C, 1.5 min
120 °C, 3 min
Product (yield, %)a
14 (60)
At first, we explored the possibility to cyclize compound
1 with hydrazine under microwave irradiation. Unfortu-
nately, we obtained low yield of the required compound
together with different amounts of the 1-amino pyrrole8 6
(Scheme 1). Different reaction conditions were tried; best
results were obtained carrying out the microwave-assisted
cyclocondensation in AcOH at 110 °C for ten minutes.9
7; t-Bu, p-ClPh
8; t-Bu, PhCH2CH2
9; Me, Pr
15 (49)
16 (58)
17 (48)
10; Et, Pr
18 (52)
11; Ph, PhCH2
12; Ph, p-MeOPh
13; Ph, p-ClPh
150 °C, 3 min
19 (65)
150 °C, 3 min
20 (52)
SYNLETT 2005, No. 18, pp 2743–2746
0
3
.1
1
.2
0
0
5
150 °C, 3 min
21 (54)
Advanced online publication: 10.10.2005
DOI: 10.1055/s-2005-918926; Art ID: D19705ST
© Georg Thieme Verlag Stuttgart · New York
a Yields of isolated and fully characterized products.

2744
G. Minetto et al.
LETTER
Starting from g-keto esters 7–13, obtained as described for moved with HBr and the amino group coupled with two
compound 2,6 pyridazines 14–21 were obtained in accept- acyl chlorides to give products 35 and 36 in 64% and 54%
able yield (see Table 1). The molecular diversity at posi- yield, respectively, starting from pyridazine 34. This last
tions 3 and 6 come from the b-keto ester and the aldehyde transformation demonstrates the versatility of our synthe-
employed in the functional homologation, while the car- sis for the application to the preparation of parallel arrays
boxymethyl group in position 4 could be used for a further of differently decorated pyridazine scaffolds.
increase of diversity. Thus, we tried to carry out a direct
amidation of the ester function using primary or second-
COOEt
1) Et2Zn, CH2I2
PhCHO
2) PCC, SiO2
COOH
ref. 14
ary amines and AlMe3 without success.12 Consequently,
the carboxymethyl groups of compounds 15, 16 and 19
(Table 2) were hydrolyzed and the amides 22–30 formed
by coupling mediated by DMTMM.13
N
O
Cbz
N
32
31
Cbz
COOEt
Ph
COOH
Ph
Table 2 Pyridazines Amides
1) NH2NH2·H2O
MW, AcOH, DDQ
2) NaOH/EtOH
Pyridazine
ester
Amine
Pyridazine amides
(yield, %)a
O
O
N
N
33
34
15
15
15
PhCH2NH2
22 (86)
23 (80)
24 (86)
N
Cbz
N
Me2CHCH2NH2
Cbz
H
O
N
Ph
1) DMTMM, NMM, PhCH2NH2
2) HBr, H2O followed by RCOCl
Ph
16
16
16
PhCH2NH2
25 (79)
26 (82)
27 (77)
N
N
Me2CHCH2NH2
35 R = PhCH2CH2–
36 R = Ph–
N
R
O
19
19
19
PhCH2NH2
28 (72)
29 (70)
30 (84)
Scheme 2
Me2CHCH2NH2
In conclusion, we have described a new rapid entry to
polyfunctionalized pyridazines and to a versatile py-
ridazine scaffold for parallel synthesis. With this method-
ology it is possible to prepare various pyridazine with
interesting biological activity that will be reported else-
where.
a Yields of crude product (calculated on the starting ester) with a
purity of at least 90% (NMR analysis).
Finally, the synthetic protocol described here was used to
prepare the pyridazine scaffold 34 suitable for double
decoration at the side chain in position 6 and in position 4.
g-N-Methylaminobutyric acid was protect as Cbz (31)
and transformed into the b-keto ester 32 with the method
Methyl 6-tert-Butyl-3-(4-chlorophenyl)pyridazine-4-carboxy-
late (15) – General Procedure
Product 7 (140 mg 0.45 mmol)6 was dissolved in 0. 35 mL of AcOH
in a vial equipped with a stirrer bar and a reflux condenser. Hydra-
zine hydrate (0.110 mL, 2.25 mmol) and DDQ (0.150 g, 0.68 mmol)
were added. The flask was inserted into the cavity of a Discovery
Microwave System apparatus (from CEM) and heated at 100 W for
1.5 min (internal temperature and pressure: 120 °C, 250 psi). The
solution was diluted with EtOAc, filtered and washed two times
with a sat. solution of NaHCO3. The organic layer was dried over
anhyd Na2SO4 and the solvent evaporated. The crude oil was puri-
fied by flash chromatography (PE–EtOAc, 4:1) to obtain the prod-
uct 15 (60% yield). 1H NMR (200 MHz, CDCl3): d = 1.47 (s, 9 H,
t-Bu), 3.74 (s, 3 H, COOMe), 7.41 (d-like, 2 H, Ar), 7.55 (d-like, 2
H, Ar), 7.74 (s, 1 H, Ar). ES-MS: m/z = 305 [M+ + 1].
of
Masamune
[carbonyl
diimidazole
(CDI),
CH(COOMe)COOH, (EtO)2Mg].14 Reaction of 32 with
Et2Zn/CH2I2 and benzaldehyde afforded compound 33
that was cyclized under standard conditions to give com-
pound 34 (31% overall yield, Scheme 2). Then we tried to
carry out Cbz deprotection using different conditions [H2,
Pd/C or Pd(OH)2/C; transfer hydrogenolysis with Pd/
cyclohexadiene or Pd/ammonium formate in different
solvents] but in all cases we obtained a compound with a
mass spectrum corresponding to the product of partial re-
duction of the pyridine ring. Thus, the carboxymethyl
group was first transformed into the corresponding amide
under standard conditions (hydrolysis and coupling as for
compounds 22–30) and finally the Cbz group was re-
Methyl 6-tert-Butyl-3-phenylpyridazine-4-carboxylate (14)
1H NMR (200 MHz, CDCl3): d = 1.34 (s, 9 H, t-Bu), 3.63 (s, 3 H,
COOMe), 7.30–7.34 (m, Ar), 7.44–7.49 (m, Ar). ES-MS: m/z = 271
[M+ + 1].
Synlett 2005, No. 18, 2743–2746 © Thieme Stuttgart · New York

LETTER
Microwave-Assisted Synthesis of Polysubstituted Pyridazines
2745
Methyl 6-tert-Butyl-3-(2-phenylethyl)pyridazine-4-carboxylate
(16)
Amide 23
1H NMR (200 MHz, CDCl3): d = 0.98 (d, 3 H, J = 7.0 Hz, Me), 1.10
(d, 3 H, J = 7.0 Hz, Me), 1.18 (s, 9 H, t-Bu), 2.23 (m, 1 H, CH), 4.12
(d, 2 H, J = 7.0 Hz, CH2) 7.09–7.40 (m, 5 H, Ar), 8.00 (br s, 1 H,
NH). ES-MS: m/z = 346, 348 [M+ + 1].
1H NMR (200 MHz, CDCl3): d = 1.46 (s, 9 H, t-Bu), 3.15 (t, 2 H,
J = 6.5 Hz, CH2), 3.55 (t, 2 H, J = 6.5 Hz, CH2), 3.92 (s, 3 H,
COOMe), 7.17–7.27 (m, 5 H, Ar), 7.83 (s, 1 H, Ar). ES-MS: m/z =
299 [M+ + 1], 321 [M+ + Na].
Amide 24
Methyl 6-Methyl-3-propylpyridazine-4-carboxylate (17)
1H NMR (200 MHz, CDCl3): d = 0.97 (t, 3 H, J = 7.0 Hz, Me),
1.60–1.83 (m, 2 H, CH2), 2.71 (s, 3 H, Me), 3.24 (t, 2 H, J = 7.0 Hz,
CH2), 3.93 (s, 3 H, COOMe), 7.62 (s, 1 H, Ar). ES-MS: m/z = 195
[M+ + 1], 217 [M+ + Na].
1H NMR (200 MHz, CDCl3): d = 1.15 (s, 9 H, t-Bu), 2.46 (m, 2 H,
CH2), 2.51 (m, 4 H, CH2), 4.10 (m, 2 H, CH2), 4.33 (m, 4 H, CH2)
7.00–7.40 (m, 5 H, Ar), 7.86 (br s, 1 H, NH). ES-MS: m/z = 403,
405 [M+ + 1].
Amide 25
Methyl 6-Ethyl-3-propylpyridazine-4-carboxylate (18)
1H NMR (200 MHz, CDCl3): d = 0.99 (t, 3 H, J = 7.0 Hz, Me), 1.37
(t, 3 H, J = 7.0 Hz, Me), 1.61–1.86 (m, 2 H, CH2), 3.03 (q, 2 H,
J = 7.0 Hz, CH2), 3.23 (t, 2 H, J = 7.0 Hz, CH2), 3.94 (s, 3 H,
COOMe), 7.61 (s, 1 H, Ar). ES-MS: m/z = 209 [M+ + 1], 231 [M+ +
Na].
1H NMR (200 MHz, CDCl3): d = 1.14 (s, 9 H, t-Bu), 3.10 (t, J = 7.0
Hz, 2 H, CH2), 3.66 (t, J = 7.0 Hz, 2 H, CH2) 5.08 (s, 2 H, CH2),
7.10–7.40 (m, 11 H, Ar), 8.16 (br s, 1 H, NH). ES-MS: m/z = 374
[M+ + 1].
Amide 26
1H NMR (200 MHz, CDCl3): d = 0.90 (d, 3 H, J = 7.0 Hz, Me), 1.08
(d, 3 H, J = 7.0 Hz, Me), 1.18 (s, 9 H, t-Bu), 2.23 (m, 1 H, CH), 3.10
(t, J = 7.0 Hz, 2 H, CH2), 3.66 (t, J = 7.0 Hz, 2 H, CH2), 4.12 (d, 2
H, J = 7.0 Hz, CH2), 7.20–7.40 (m, 6 H, Ar), 7.76 (br s, 1 H, NH).
ES-MS: m/z = 340 [M+ + 1].
Methyl 6-Phenyl-3-benzylpyridazine-4-carboxylate (19)
1H NMR (200 MHz, CDCl3): d = 3.95 (s, 3 H, CH3), 4.70 (s, 2 H,
CH2), 7.15–7.50 (m, Ar), 8.01–8.11 (m, Ar). ES-MS: m/z = 319
[M+ + 1], 327 [M+ + Na].
Methyl 6-Phenyl-3-(4-methoxyphenyl)pyridazine-4-carboxy-
late (20)
Amide 27
1H NMR (200 MHz, CDCl3): d = 1.15 (s, 9 H, t-Bu), 2.46 (m, 2 H,
CH2), 2.51 (m, 4 H, CH2), 3.10 (t, J = 7.0 Hz, 2 H, CH2), 3.66 (t,
J = 7 Hz, 2 H, CH2), 4.10 (m, 2 H, CH2), 4.33 (m, 4 H, CH2), 7.10–
7.40 (m, 6 H, Ar), 7,59 (br s, 1 H, NH). ES-MS: m/z = 397 [M+ + 1].
1H NMR (200 MHz, CDCl3): d = 3.85 (s, 3 H, OMe), 3.95 (s, 3 H,
OMe), 6.97–7.02 (m, Ar), 7.49–7.69 (m, Ar), 8.05 (s, 1 H, Ar),
8.12–8.17 (m, Ar). ES-MS: m/z = 321 [M+ + 1].
Methyl 6-Phenyl-3-(4-chlorophenyl)pyridazine-4-carboxylate
(21)
Amide 28
1H NMR (200 MHz, CDCl3): d = 3.60 (s, 2 H, CH2), 5.18 (s, 2 H,
CH2), 7.00–7.50 (m, 16 H, Ar), 8.00 (br s, 1 H, NH). ES-MS: m/z =
380 [M+ + 1].
1H NMR (200 MHz, CDCl3): d = 3.95 (s, 3 H, CH3), 4.70 (s, 2 H,
CH2), 7.15–7.50 (m, Ar), 8.01–8.11 (m, Ar). ES-MS: m/z = 325
[M+ + 1], 347 [M+ + Na].
Amide 29
Ethyl 3-Phenyl-6-(3-N-methyl-N-carbobenzyloxypropyl)py-
ridazine-4-carboxylate (34)
1H NMR (200 MHz, CDCl3): d = 0.92 (d, 3 H, J = 7.0 Hz, Me), 1.06
(d, 3 H, J = 7.0 Hz, Me), 2.23 (m, 1 H, CH), 3.65 (s, 2 H, CH2),
4.12 (m, 2 H, CH2), 7.00–7.50 (m, 11 H, Ar), 8.01 (br s, 1 H, NH).
ES-MS: m/z = 346 [M+ + 1].
1H NMR (200 MHz, CDCl3): d = 1.09 (t, 3 H, J = 6.9 Hz, Me),
2.10–2.31 (m, 2 H, CH2), 2.92 (s, 3 H, Me), 2.98–3.11 (m, 2 H,
CH2), 3.41 (t, 2 H, J = 6.8 Hz, CH2), 4.15 (q, 2 H, J = 6.9 Hz, CH2),
5.11 (s, 2 H, CH2), 7.16–7.35 (m, Ar), 7.40–7.49 (m, Ar), 7.50–7.61
(m, Ar). ES-MS: m/z = 434 [M+ + 1], 456 [M+ + Na].
Amide 29
1H NMR (200 MHz, CDCl3): d = 2.40 (m, 2 H, CH2), 2.58 (m, 4 H,
CH2), 3.54 (s, 2 H, CH2), 4.18 (m, 2 H, CH2), 4.37 (m, 4 H, CH2),
7.10–7.40 (m, 11 H, Ar), 7.70 (br s, 1 H, NH). ES-MS: m/z = 403
[M+ + 1].
6-tert-Butyl-N-benzyl-3-(4-chlorophenyl)pyridazine-4-carbox-
amide (22) – General Procedure
Pyridazine 14 (30 mg, 0.094 mmol) was dissolved in 4 mL of a 3:1
EtOH–H2O solution containing 85 mg of KOH, and the solution
was stirred at 90 °C for 4 h. Then, the solution was cooled to r.t. and
EtOH evaporated. A solution of 1 N HCl was added and the aqueous
layer was extracted three times with EtOAc. The fractions were col-
lected, dried over anhyd Na2SO4 and the solvent evaporated. The
crude was dissolved into 1 mL of THF and 27 mL of benzylamine (1
equiv), 140 mg of DMTMM (2 equiv), and 75 mg of NMM (3
equiv) were slowly added and the solution was stirred overnight.
Then, Et2O was added and the white precipitate was filtered away.
The organic phase was washed two times with a solution of HCl
(5%), two times with TEA (10%), two times with HCl (5%) again
and finally with brine. The organic layer was dried over anhyd
Na2SO4 and the solvent was evaporated to give a residue that was
purified by flash chromatography (CHCl3–EtOAc–MeOH 4:1:0.5)
to give 30 mg of product 22 (yield 66%).
Butyl 3-Phenyl-6-(3-N-methyl–N-(2-phenylpropionyl)pro-
pyl)pyridazine-4-carboxamide (35)
Compound 24 (200 mg, 0.43 mmol), was stirred at r.t. and 700 mL
of a 33% solution of HBr in AcOH were added slowly. After 30
min, CHCl3 (1 mL) was added; the reaction was filtered and washed
with a solution of sat. NaHCO3. The aqueous phase was washed
three times with CHCl3; the organic layers were collected, washed
with brine and dried over anhyd Na2SO4. The solvent was removed
and the crude was used in the next step. This crude product (80 mg,
0,24 mmol) was dissolved in 5 mL of dry CH2Cl2; 40 mL of 3-phe-
nylpropionyl chloride (0.27 mmol), 38 mL of TEA, a catalytic
amount of DMAP was added and the solution was stirred at r.t. for
1.5 h. The organic phase was washed with a 1 M solution of HCl and
then with brine. The organic layer was dried over anhyd Na2SO4 and
the solvent was evaporated. The crude oil was purified by flash
chromatograpy (CHCl3–EtOAc 4:1) to obtain 70 mg of product 35
(yield 65%).
1H NMR (200 MHz, CDCl3): d = 1.14 (s, 9 H, t-Bu), 5.03 (s, 2 H,
CH2), 6.94–6.98 (m, 4 H, Ar), 7.09–7.40 (m, 4 H, Ar), 7.54 (m, 2 H,
Ar), 8.06 (br s, 1 H, NH). ES-MS: m/z = 380, 382 [M+ + 1].
Synlett 2005, No. 18, 2743–2746 © Thieme Stuttgart · New York

2746
G. Minetto et al.
LETTER
1H NMR (200 MHz, CDCl3): d = 0.77–0.84 (m, 3 H Me), 1.00–1.39
(m, 4 H, CH2), 1.72–1.97 (m, 2 H, CH2), 2.03–2.20 (m, 2 H, CH2),
2.46–2.65 (m, 2 H, CH2), 2.83–3.20 (m, 7 H), 3.30–3.41 (m, 4 H,
CH2), 7.07–7.30 (m, Ar), 7.38–7.55 (m, Ar), 7.68–7.75 (m, Ar),
8.00 (br s, 1 H, NH). 13C NMR (75 MHz, CDCl3): d = 13.5, 19.8,
25.3, 26.4, 27.3, 29.5, 30.7, 30.8, 31.2, 31.5, 31.7, 32.6, 32.7, 32.3,
34.8, 35.2, 35.3, 39.7, 46.8, 47.0, 49.1, 56.9, 125.3, 125.5, 126.0,
126.1, 126.8, 128.2, 128.3, 128.4, 128.5, 128.9, 129.0, 129.3, 129.5,
133.9, 135.9, 141.0, 141.2, 155.6, 161.0, 161.5, 165.8, 166.1, 172.1,
172.2. ES-MS: m/z = 459 [M+ + 1], 481 [M+ + Na].
Bouguignon, J. J.; Ramstrom, H.; Haiech, J.; Van Eldick, L.
J.; Watterson, D. M. J. Med. Chem. 2002, 45, 563.
(f) Contreras, J.-M.; Parrot, I.; Sippl, W.; Rival, Y. M.;
Wermuth, C. G. J. Med. Chem. 2001, 44, 2707. (g) Curtet,
S.; Soulier, J.-L.; Zahradnik, I.; Giner, M.; Berque-Bestel, I.;
Mialet, J.; Lezoualc’h, F.; Donzeau-Gouge, P.; Sicsic, S.;
Fischmeister, R.; Langlois, M. J. Med. Chem. 2000, 43,
3761.
(4) (a) Coelho, A.; Sotelo, E.; Novoa, H.; Peeters, O. M.; Blaton,
N.; Raviña, E. Tetrahedron Lett. 2004, 45, 3459.
(b) Marriner, G. A.; Garner, S. A.; Jang, H.-Y.; Krische, M.
J. J. Org. Chem. 2004, 69, 1380.
Butyl 3-Phenyl-6-(3-N-methyl-N-benzoylpropyl)pyridazine-4-
carboxamide (36)
Yield 65%. H NMR (200 MHz, CDCl3): d = 0.73 (t, 3 H, J = 7.0
(5) (a) Parrot, I.; Ritter, G.; Wermuth, C. G.; Hibert, M. Synlett
2002, 1123. (b) Sotelo, E.; Raviña, E. Synlett 2002, 223.
(c) Guery, S.; Parrot, I.; Rival, Y.; Wermuth, C. G. Synthesis
2001, 595. (d) Dal Piaz, V.; Capperucci, A. Synlett 1998,
762. (e) Draper, T. L.; Bailey, T. R. J. Org. Chem. 1995, 60,
748. For a review on metallation of pyridazines, see:
(f) Turk, A.; Plé, N.; Mongin, F.; Quéguiner, G. Tetrahedron
2001, 57, 4489. (g) Mongin, F.; Quéguiner, G. Tetrahedron
2001, 57, 4059.
1
Hz, Me), 0.92–1.26 (m, 4 H, CH2), 1.98–2.14 (m, 2 H, CH2), 2.80–
3.10 (m, 5 H, CH2 and Me), 3.35–3.56 (m, 2 H, CH2), 7.05–7.45 (m,
Ar), 7.51–7.63 (m, Ar), 8.00 (d-like, 2 H, Ar), 8.31 (br s, 1 H, NH).
13C NMR (75 MHz, CDCl3): d = 13.4, 14.0, 19.7, 20.8, 26.1, 30.6,
32.8, 35.1, 37.4, 39.5, 46.5, 56.8, 60.2, 125.4, 126.6, 128.1, 128.2,
128.3, 128.7, 128.8, 129.2, 129.4, 129.7, 132.6, 134.1, 135.8, 136.1,
136.3, 143.4, 155.7, 161.1, 166.1, 171.4. ES-MS: m/z = 431 [M+ +
1], 453 [M+ + Na].
(6) Minetto, G.; Raveglia, L. F.; Taddei, M. Org. Lett. 2004, 6,
389.
(7) Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Organic
Chemistry; Oxford University Press: Oxford, 2001, 1195.
(8) Stetter, H.; Jonas, F. Chem. Ber. 1981, 114, 564.
(9) A monomode Discover system from CEM was employed
using a sealed vial with a maximun pressure internal control
of 250 psi.
(10) Raghavan, S.; Anuradha, K. Synlett 2003, 711.
(11) Attanasi, O. A.; Filippone, P.; Fiorucci, C.; Mantellini, F.
Synlett 1997, 1361; and references cited therein.
(12) (a) Basha, A.; Lipton, M.; Weinreb, S. M. Tetrahedron Lett.
1977, 18, 4171. (b) See also: Rodriquez, M.; Sega, A.;
Taddei, M. Org. Lett. 2003, 5, 4029.
Acknowledgment
This work was financially supported by Nikem Research (Milan).
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Synlett 2005, No. 18, 2743–2746 © Thieme Stuttgart · New York