Sulfur ylides 10. Modified method for the synthesis of pyrrolizine- and indolizinediones

Article abstract of DOI:10.1023/A:1015054907007

A modified method for the synthesis of derivatives of pyrrolizinedione and iridolizinedione was proposed. The method is based on the intramolecular cyclization of keto-stabilized sulfur ylides generated in situ from diazo ketones and Me2S in the presence of Rh2(OAc)4.

Full text of DOI:10.1023/A:1015054907007

Russian Chemical Bulletin, International Edition, Vol. 51, No. 1, pp. 189—190, January, 2002
189
Sulfur ylides
10.* Modified method for the synthesis of pyrrolizineꢀ and indolizinediones
b
b
S. N. Lakeev,a I. Z. Mullagalin,b I. O. Maidanova,a F. Z. Galin, and G. A. Tolstikov

aInstitute of Biology, Ufa Research Center of the Russian Academy of Sciences,
69 prosp. Oktyabrya, 450054 Ufa, Russian Federation.
Fax: +7 (347 2) 35 2641. Eꢀmail: irina_m@anrb.ru
bInstitute of Organic Chemistry, Ufa Research Center of the Russian Academy of Sciences,
71 prosp. Oktyabrya, 450054 Ufa, Russian Federation.
Fax: +7 (347 2) 35 6066. Eꢀmail: galin@anrb.ru
A modified method for the synthesis of derivatives of pyrrolizinedione and indolizinedione
was proposed. The method is based on the intramolecular cyclization of ketoꢀstabilized sulfur
ylides generated in situ from diazo ketones and Me2S in the presence of Rh2(OAc)4.
Key words: ketoꢀstabilized sulfonium ylides, diazo ketone, dimethyl sulfide, Rh2(OAc)4,
intramolecular cyclization, 3ꢀbenzylꢀ1ꢀmethylthioꢀ3Hꢀpyrrole[2,1ꢀa]isoindoleꢀ2,5ꢀdione,
1ꢀmethylthioꢀ3,4ꢀdihydropyrido[2,1ꢀa]isoindoleꢀ2,6ꢀdione.
Earlier,2,3 we have developed a method for the synꢀ
thesis of pyrrolizinedione 1 and indolizinedione 2 through
intramolecular cyclization of sulfur ylides 3, which are
derived from αꢀ and βꢀ(Nꢀphthaloyl)amino acids 4. The
method includes the conversion of Nꢀprotected amino
acids 4 into acid chlorides, which react with CH2N2 to
give diazo ketones 5. The latter are treated succesꢀ
sively with HBr and Me2S to form sulfonium salts 6,
whose deprotonation yields the corresponding ylides 3
(Scheme 1).
It is known4 that sulfur ylides can also be obtained
immediately from diazo compounds by reacting them with
sulfides in the presence of catalysts, usually Rh or Cu
compounds. To simplify the scheme of preparing cyclizaꢀ
tion products 1 and 2 and increase their yields, we studied
the intramolecular cyclization of sulfur ylides 3 generated
Scheme 1
Reagents and conditions: i. SOCl2; ii. CH2N2; iii. HBr; iv. Me2S; v. NaOH, K2CO3, CHCl3; vi. BzOH, PhMe, 110 °C; vii. Me2S,
Rh2(OAc)4, PhMe, 40 °C.
* For Part 9, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 177—178, January, 2002.
1066ꢀ5285/02/5101ꢀ189 $27.00 © 2002 Plenum Publishing Corporation

190
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 1, January, 2002
Lakeev et al.
10 mL of anhydrous toluene. The crimson reaction mixture was
stirred at 40 °C until the diazo ketone was completely consumed
(TLC, CHCl3—Me2CO (9 : 1), visualization with ninhydrin).
The solution gradually turned yellow. Then BzOH (0.25 g,
2.05 mmol) was added, and the resulting solution was refluxed
for 1 h. The solvent was evaporated, and the products were
isolated by column chromatography (AcOEt—hexane, 1 : 1).
The yields of compounds 1 and 2 were 63 and 68%, respectively.
The spectral characteristics of the products are consistent with
the previous data.3
in situ from diazo ketones 5 and Me2S in the presence of
Rh2(OAc)4. A mixture of diazo ketone 5 and Me2S with a
catalytic amount of Rh2(OAc)4 was heated in toluene at
40 °C until the diazo ketone was completely consumed
(monitoring by TLC). Then a necessary amount of benꢀ
zoic acid was added, and cyclization was carried out unꢀ
der reflux.
Thus, we shortened the original scheme by three steps
and performed cyclization without isolating ylides from
the reaction mixture. As a result, the yields of pyrrolizineꢀ
dione 1 and indolizinedione 2 from the starting diazo
ketones were increased by about 20% (from 41 to 63%
for 1 and from 49 to 68% for 2).
This work was financially supported by the State Proꢀ
gram for Support of Leading Scientific Schools (Project
No. 00ꢀ15ꢀ97325).
References
Experimental
1. V. K. Mavrodiev, I. I. Furlei, S. N. Lakeev, F. Z. Galin, and
G. A. Tolstikov, Izv. Akad. Nauk, Ser. Khim., 1999, 2100
[Russ. Chem. Bull., 1999, 48, 2077 (Engl. Transl.)].
2. G. A. Tolstikov, F. Z. Galin, S. N. Lakeev, L. M. Khalilov,
and V. S. Sultanova, Izv. Akad. Nauk SSSR, Ser. Khim., 1990,
612 [Bull. Acad. Sci. USSR, Div. Chem. Sci., 1990, 39, 535
(Engl. Transl.)].
3. F. Z. Galin, S. N. Lakeev, and G. A. Tolstikov, Izv. Akad.
Nauk, Ser. Khim., 1996, 165 [Russ. Chem. Bull., 1996, 45, 156
(Engl. Transl.)].
4. A. Padwa and S. F. Hornbuckle, Chem. Rev., 1991, 91, 263.
5. L. M. Zubritskii, Gomogennoꢀkataliticheskie reaktsii neꢀ
predel´nykh soedinenii [GomogeneousꢀCatalytic Reactions of Unꢀ
saturated Compounds], Izdꢀvo LTI, Leningrad, 1987, 85 (in
Russian).
The course of the reaction was monitored and the purity of
the products was checked by TLC on Silufol UVꢀ254 plates
(visualization under UV light or by heating the plates with a
sprayed solution of ninhydrin to 100—120 °C). The reaction
products were isolated by column chromatography on silica gel.
Me2S and BzOH (both highꢀpurity grade) were used withꢀ
out additional purification. Toluene was refluxed over Na and
distilled. The other solvents were purified by distillation. The
catalyst Rh2(OAc)4 was prepared according to the known proꢀ
cedure.5 The starting diazo ketones were synthesized as described
in Ref. 2.
3ꢀBenzylꢀ1ꢀmethylthioꢀ3Hꢀpyrrolo[2,1ꢀa]isoindoleꢀ2,5ꢀdione
(1) and 1ꢀmethylthioꢀ3,4ꢀdihydropyrido[2,1ꢀa]isoindoleꢀ2,6ꢀdione
(2) (general procedure). Rhodium acetate Rh2(OAc)4 (0.004 g,
0.009 mmol) was added in one portion to a stirred solution of
diazo ketone 5 (2.05 mmol) and Me2S (1 g, 16.10 mmol) in
Received August 30, 2001