Rare earth triflate-catalyzed addition reactions of acylhydrazones with silyl enolates. A facile synthesis of pyrazolone derivatives

Article abstract of DOI:10.1055/s-1998-1638

In the presence of a catalytic amount of a rare earth triflate, benzoylhydrazones reacted with silyl enolates to afford the corresponding β-N′-benzoylhydrazino esters in high yields. The hydrazino esters thus obtained were readily converted to pyrazolone derivatives by treatment with a base. A three-component reaction between an aldehyde, an acylhydrazine, and a silyl enolate was also performed successfully.

Full text of DOI:10.1055/s-1998-1638

March 1998
SYNLETT
249
Rare Earth Triflate-Catalyzed Addition Reactions of Acylhydrazones with Silyl Enolates. A
Facile Synthesis of Pyrazolone Derivatives
Hidekazu Oyamada and Shu Kobayashi*
Department of Applied Chemistry, Faculty of Science, Science University of Tokyo (SUT), Japan, and CREST, Japan Science and Technology
Corporation (JST), Kagurazaka, Shinjuku-ku, Tokyo 162, Japan
Fax +81(3)32604726
Received 14 October 1997
Abstract: In the presence of a catalytic amount of a rare earth triflate,
benzoylhydrazones reacted with silyl enolates to afford the
corresponding β-N'-benzoylhydrazino esters in high yields. The
hydrazino esters thus obtained were readily converted to pyrazolone
derivatives by treatment with a base. A three-component reaction
between an aldehyde, an acylhydrazine, and a silyl enolate was also
performed successfully.
In Lewis acid-mediated reactions of nitrogen-containing compounds,
many Lewis acids are deactivated or sometimes decomposed by the
nitrogen atoms of the starting materials or products, and even when the
desired reactions proceed, more than stoichiometric amounts of the
Lewis acids are needed because the acids are trapped by the nitrogen
1
atoms. It is desirable from a synthetic point of view that nitrogen-
containing compounds are activated by Lewis acids catalytically.
Recently, we have found that rare earth triflates are effective for the
2
catalytic activation of nitrogen-containing compounds. For example,
rare earth triflates activate aldehydes containing nitrogen atoms or
aldimines catalytically, and elegant carbon-carbon bond-forming
reactions have been realized using these catalytic systems. The catalytic
use of rare earth triflates is rationalized by the equilibrium of the Lewis
acids-nitrogen atoms coordination. This is similar to the equilibrium of
rare earth triflates-water coordination, which enables the Lewis acids to
3
be stable in water without hydrolysis. In the course of our
investigations to explore the utility of rare earth triflates in synthesis, we
further studied the activation of other useful nitrogen-containing
compounds by rare earth triflates. In this paper, we describe the catalytic
activation of acylhydrazones by rare earth triflates, which react with
silyl enolates smoothly to afford β-N'-benzoylhydrazino ester
derivatives.
We found that benzaldehyde benzoylhydrazone reacted with the silyl
4
enolate derived from methyl isobutyrate, in the presence of a catalytic
amount of scandium triflate (Sc(OTf) ). The reaction proceeded most
3
efficiently in acetonitrile at -20 °C to afford the corresponding β-N'-
benzoylhydrazino ester. Other benzoylhydrazones were then examined
and the results are summarized in Table 1. Not only aromatic but also
aliphatic, unsaturated aldehyde, and glyoxylate benzoylhydrazones
worked well. In most cases, the reactions proceeded smoothly at 0 °C to
rt for 1-2 h to afford the corresponding β-N'-benzoylhydrazino ester
derivatives in high yields, although some yields were not optimized. As
for silyl enolates, t-butyldimethylsilyl enolates reacted smoothly, and
the silyl enolates derived from esters as well as thioesters also gave
good results. It is noted that catalytic activation of the basic
5,6
interesting class of compounds, and these reactions provide a useful
route for the preparation of such derivatives.
Finally, a three-component reaction of an aldehyde, a hydrazine, and a
silyl enolate was examined, bearing in mind the application of these
reactions to the synthesis of a pyrazolone library. It was found that in
7,8
benzoylhydrazones has been achieved by using Sc(OTf) as a Lewis
3
the presence of a catalytic amount of ytterbium triflate (Yb(OTf) ) and
acid catalyst, and that typical Lewis acids such as TiCl , SnCl ,
3
4
4
Drierite, benzaldehyde reacted with benzoylhydrazine and the t-
butyldimethylsilyl enolate smoothly in acetonitrile at -20 °C to rt, to
afford the desired β-N'-benzoylhydrazino ester in a 92% yield (Scheme
BF OEt , etc. were not effective in this reaction (Table 2).
3•
2
The β-N'-benzoylhydrazino esters obtained were readily converted to
9
2).
5
the pyrazolone derivatives. Thus, treatment of the hydrazino ester
derivatives with NaOMe in MeOH at 70 °C promoted the cyclization
smoothly, and the corresponding pyrazolone derivatives were obtained
in excellent yields (Scheme 1). Pyrazolone derivatives are a biologically
A typical experimental procedure is described for the reaction of
isobutyroaldehyde benzoylhydrazone (1) with the trimethylsilyl enolate

250
LETTERS
SYNLETT
(2) (a) Kobayashi, S.; Araki, M.; Ishitani, H.; Nagayama, S.; Hachiya,
I. Synlett 1995, 233. (b) Kobayashi, S.; Ishitani, H.; Nagayama, S.
1995, 1195. (c) Kobayashi, S.; Araki, M.; Yasuda, M.
Synthesis
1995, , 5773.
36
Tetrahedron Lett.
(3) (a) Kobayashi, S.; Wakabayashi, T.; Nagayama, S.; Oyamada, H.
1997, , 4559. (b) Kobayashi, S.; Wakabayashi,
Tetrahedron Lett.
38
T.; Oyamada, H. Chem. Lett. 1997, 831. (c) Kobayashi, S. Synlett
1994, 689. (d) Kobayashi, S.; Hachiya, I. 1994,
J. Org. Chem.
59,
3590. (e) Kobayashi, S.; Hachiya, I.; Yamanoi, Y. Bull. Chem. Soc.
1994, , 2342. (f) Kobayashi, S.; Hachiya, I.
Jpn.
Lett.
67
Tetrahedron
1992, , 1625. (g) Kobayashi, S.
33
1991, 2187.
Chem. Lett.
(4) Reviews: (a) Rasmussen, J. K. Synthesis 1977, 91. (b) Fleming, I.
1980, , 265. (c) Brownbridge, P. 1983, 1; 85.
Chimia
34
Synthesis
(d) Weber, W. P. Silicon Reagents for Organic Synthesis; Springer-
Verlag: Berlin, 1983. (e) Colvin, E. W. Silicon in Organic
Synthesis; Butterworths: London, 1981. (f) Kleinnman, E. F.
Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon
Press: New York, 1991; Vol. 2, p 167.
(5) (a) Elgureo, J. Comprehensive Heterocyclic Chemistry; Katritzky,
A. R.; Rees, C. W., Eds.; Pergamon Press: Oxford, 1984, Vol. 5,
Chapter 4.04. (b) Claramunt, R. M.; Elguero, J., Org. Prep. Proc.
1991, 23, 273. (c) Attanasi, O. A.; Crescentini, L. D.; Filippone,
Int.
P.; Foresti, E.; Galeazzi, R.; Ghiviriga, I.; Katritzky, A. R.
1997,
, 5617. (d) Kost, A. N.; Grandberg, I. I.
Tetrahedron
53
Advances in Heterocyclic Chemistry; Katritzky, A. R., Ed.;
Academic Press: New York, Vol. 6, p. 347, 1996.
(6) (a) Kees, K.L.; Caggiano, T. J.; Steiner, K. E.; Fitzgerald, J. J.;
Kates, M. J.; Christos, T. E.; Kulishoff, J. M.; Moore, R. D.;
McCaleb, M. L. J. Med. Chem. 1995, 38, 617. (b) Lednicer, D. The
Organic Chemistry of Drug Synthesis, John Wiley & Sons: New
York, 1995. (c) Blaney, J. M.; Hansch, C. Comprehensive
Medicinal Chemistry; Hansch, C.; Sammes, P. G.; Taylor, J. B.;
Ramsden, C. A., Eds.; Pergamon Press: Oxford, 1990.
derived from methyl isobutyrate (2): To a mixture of Sc(OTf) (9.8 mg,
3
0.02 mmol, 5 mol%) and 1 (82 mg, 0.4 mmol) in CH CN (1.5 ml) were
3
added 2 (105 mg, 0.6 mmol) in CH CN (0.5 ml) at 0 °C. After the
3
mixture was stirred for 1 h, aqueous sat. NaHCO was added and the
3
product was extracted with dichloromethane. After the organic layer
was dried and evaporated, the crude product was chromatographed on
silica
gel
to
afford
methyl
3-N'-benzoylhydrazino-2,2,5-
10
(7) (a) Ugi, I.; Dömling, A.; Hörl, W. Endeavour 1994, 18, 115.
(b) Armstrong, R.; Combs, A. P.; Tempest, P. A.; Brown, S. D.;
Keating, T. A. Acc. Chem. Res. 1996, 29, 123. (c) Tempest, P. A.;
Brown, S. D.; Armstrong, R. W. Angew. Chem., Int. Ed. Engl. 1996,
trimethylhexanoate (3, 118 mg, 96% yield). To a MeOH solution of 3
(31 mg, 0.10 mmol) was added NaOMe (16 mg, 0.30 mmol) at rt. The
mixture was stirred for 2 h at 70 °C, and Amberlite IRC-76 resin was
added to quench the reaction at 0 °C. After a usual work up, the desired
1995,
36,
11
35, 640. (d) Wipf, P.; Cunningham, A. Tetrahedron Lett.
pyrazolone (4) was obtained in a 87% yield (15 mg).
7819. (e) Ugi, I.; Demharter, A.; Hörl, W.; Schmid, T. Tetrahedron
In
summary,
rare
earth
triflate-catalyzed
reactions
of
1996, , 11657.
52
benzoylhydrazones with silyl enolates proceeded smoothly to afford the
corresponding β-N'-benzoylhydrazino esters, which were readily
converted to pyrazolone derivatives by treatment with a base in high
(8) (a) Kobayashi, S.; Araki, M.; Yasuda, M. Tetrahedron Lett. 1995,
36, 5773. (b) Kobayashi, S.; Ishitani, H.; Nagayama, S. Chem. Lett.
1995, 423. (c) Kobayashi, S.; Nagayama, S.
J. Am. Chem. Soc.
, 8977. (d) Kobayashi, S.; Moriwaki, M.; Akiyama, R.;
yields.
A three-component reaction between an aldehyde, an
1996,
118
acylhydrazine, and a silyl enolate was also successfully carried out.
These results have demonstrated the utility of rare earth triflates for the
catalytic activation of nitrogen-containing compounds, which is
generally difficult using typical Lewis acids. Further investigations
along this line are now in progress in our laboratories.
Suzuki, S.; Hachiya, I. Tetrahedron Lett. 1996, 37, 7783.
(e) Kobayashi, S.; Nagayama, S.; Busujima, T. Tetrahedron Lett.
1996, , 9221. (f) Kobayashi, S.;
37
Akiyama, R.; Moriwaki, M.
1997, , 4819. (g) Kobayashi, S.; Iwamoto, S.;
Tetrahedron Lett.
38
Nagayam, S. Synlett 1997, 1099. (h) Kobayashi, S.; Akiyama, R.;
Kawamura, M.; Ishitani, H. Chem Lett. 1997, 1039.
Acknowledgment. This work was partially supported by a Grant-in-Aid
for Scientific Research from the Ministry of Education, Science, Sports,
and Culture, Japan, and a SUT Special Grant for Research Promotion.
(9) When Sc(OTf)3 was used under the same reaction conditions, the
desired product was obtained in a 72% yield (97% conversion).
(10) 3: Mp 84.3-84.5 °C (hexane-ethyl acetate). IR (KBr) 1728, 1640
cm-1; 1H NMR (CDCl3) δ 0.91-0.96 (m, 6H), 1.11-1.35 (m, 8H),
1.97 (m, 1H), 3.27 (dd, 1H, J = 2.1, 9.6 Hz), 3.57 (s, 3H), 4.90 (br s,
1H), 7.39-7.50 (m, 3H), 7.75 (d, 2H), 8.01 (br s, 1H).
(11) 4: IR (KBr) 3208, 1699, 1602 cm-1; 1H NMR (CDCl3) δ 0.99 (d,
6H, J = 6.4 Hz), 1.22 (s, 6H), 2.13-2.17 (m, 3H); HRMS calcd for
C9H16ON2 (M+) 168.1263, found 168.1265.
References and Notes
(1) For example, (a) Ishihara, K.; Funahashi, M.; Hanaki, N.; Miyata,
M.; Yamamoto, H. Synlett 1994, 963. (b) Onaka, M; Ohno, R.;
Yanagiya, N.; Izumi, Y. Synlett 1993, 141. (c) Mukaiyama, T.;
Akamatsu, H.; Han, J. S. Chem. Lett. 1990, 889. (d) Mukaiyama, T.;
Kashiwagi, K.; Matsui, S. Chem. Lett. 1989, 1397. (e) Guanti, G.;
Narisano, E.; Banfi, L. Tetrahedron Lett. 1987, 28, 4331. (f) Ojima,
I.; Inaba, S.; Yoshida, K. Tetrahedron Lett. 1977, 3643.