Indolizine deriv

Enantiomerically pure triene 395, whose chirality stems from that of /3-D-ribofuranosc, was transformed into the chiral pyrrolidine 396 by intramolecular iodoamination. A subsequent RCM reaction gave indolizine derivative 397. Treatment of this compound with nucleophiles afforded mixtures of indolizine and quinolizine derivatives in... 

Numerous examples of the synthesis of tricyclic systems based on indolizine derivative 232 have been reported <2000M959>. The product obtained from the reaction of 232 with carbon disulfide depends on the reaction medium. Thus, in aqueous potassium hydroxide the pyrimidine-dithione 233 is formed, whereas in pyridine the iminothiazine-thione 234 is obtained. In aqueous potassium hydroxide, compound 234 rearranges to 233 (Scheme 12) <2000M959>. 

Bipyridinium ylides 133, generated in situ from 4,4-bipyridinium diquaternary salts 133, undergo 1,3-dipolar cycloaddition with activated alkynes under micro-waves, on KF-alumina in the absence of solvent, to give 7,7-bis-indolizines 134 in 81-93% yield (Scheme 9.40) [91]. The same reactions, when performed using benzene as a solvent under classical heating, yielded 7,7-bis-indolizine derivatives in yields of only 50-60% [92],... 

The use of a higher CO pressure allowed the same intramolecular reaction starting with alkyl iodide derivatives 49 <2000TL3035> (Scheme 17, Equation 2). Without the presence of the CO atmosphere, the same reaction affords the expected indolizine derivatives 54 and 55 <1997TL7937> (Scheme 17, Equation 3). 

The radical cyclization can also involve an acrylate to obtain C02Me-substituted indolizine derivatives 57 (Scheme 18) <2000TL10181>. 

Alkenyl and alkynyl Fischer carbene complexes reacted with pyrrole imine 108 to give, through a 1,2- and 1,3-metal migration, respectively, indolizine derivatives at a different level of unsaturation (Scheme 29) <1999JA3065>. 

Allene-substituted lactams or cyclic imines are useful intermediates in the synthesis of indolizine derivatives. While the former are stable and need a Pd(0) catalyst and the presence of phenyl iodide to react < 1997TL6275>, the latter are produced in situ and react immediately (Scheme 37) <2001JA2074>. 

The condensation of DMDP with carbon disulfide/dicyclohexylcarbodiimide (DCC) afforded the indolizine derivative—potentially biological active thionocarbamate on carbohydrate scaffold, fused from the nitrogen side. 

Ring contraction to form the indolizine ring system is another side-reaction in the alkaline hydrolysis of a quinolizine ester. Acheson etal.30 have studied in detail the conversion of tetramethyl 4Zf-quinolizine-1,2,3,4-tetracarboxylate into the corresponding indolizine derivative. 

Little work has been reported. From studies of proton/deuterium exchange rates, 2-methylpyrrolo[2,l-6]thiazole (478) was estimated to have a pKa of 6.4,394 a value comparable with that of 2-methylindolizine (pKa = 5.9).394 In the same way, the basicity of 3,4-dimethylimidazo-[l,5-a]benzimidazole (468b) (pA = 6.01) resembles that of imidazo-[l,2-a]pyridines (pA = 5.05-5.96).398 It would seem, therefore, that the basicity of azapentalenes parallels that of related indolizine derivatives [Eq. (40)]. 

The cyclazine (Iv) was the only product isolated in poor yield from reaction of pyridine and methyl propiolate in acetonitrile. The indolizine derivative (35) may be an intermediate, since it was obtained from a similar reaction in ether.39 2-Acetylpyridine and ethyl pyridine-2-carboxylate reacted similarly.40... 

Better yields may be obtained from vinylpyridines and alkyl propiolates, as can be seen from the conversion of 36 to the cycl[3,2,2]-azine (lw).41 Reaction of a-(bismethylthio)methylene-2-pyridineaceto-nitrile and ethyl bromoacetate using triethylamine afforded the indolizine derivative (37). Dimethyl l-carbamoyl-2-methylthiocycl-[3,2,2]azine-3,4-dicarboxylate (Iz) was synthesized by allowing dimethyl acetylenedicarboxylate to react with indolizine derivative 38, which was obtained by decarboxylation of 37 using sulfuric acid in presence of palladium-on-charcoal as catalyst [Eq. (6)].42... 

That these along with chemical shifts are of value in the assignment of substitution pattern emerges from data on six mono- and di-methylated indolizine derivatives (64AJC1128),... 

The indolizine derivatives (57) and (58) were obtained from a reaction of indolizines with the a-oxohydroximoyl chloride (59) in the presence of triethylamine. It has been assumed that (59) is first converted into a nitrile oxide which is the effective reagent. Cyclization of the 3-(2-oxohydroximyl)indolizines (58) to yield the [2.3.3]cyclazine derivatives (60) was brought about by treatment with potassium r-butoxide (81JCS(P1)3150). 

Indolizine derivatives have been studied for their psychotropic anti-inflammatory, analgesic, antimicrobial, antiexudative and hypoglycemic activity. Mannich bases of indolizines (see Section 3.08.3.1.3) have been found to possess central nervous system depressant activity <78AHC(23)103, 77HC(30)117, 77HC(30)179>. 

The compounds (215) (80JCS(P1)1614) and (216) (81CPB390) are the only indolizine derivatives which have been found to occur naturally. 

When reacted with trimethylsilylmethyl triflate, pyridines give pyridinium methyl-ides, a salt which is a good precursor for azomethine ylids under treatment with fluoride ion. Thus, indolizine derivatives can be prepared from non-stabilized pyridinium... 

Under the amine basic conditions, the subsequently added l-(2-oxoethyl)-pyridinium bromide derivatives 90 are transformed in situ into pyridinium ylides that undergo a [2 + 3] cycloaddition with the alkynone dipolarophiles present in the reaction mixture. The initial cycloadducts instantaneously aromatize to give rise to highly fluorescent indolizine derivatives 91. 

Indolizines.2 The reagent reacts with the pyridinium salts (2) in the presence of N(C2H5)3 to give the indolizine derivatives 3 and 4. When R = CH, 4 is not formed. 

Table 1 Bond Lengths riif of Indolizine Derivatives (7) and (8)a...

A cyclic enaminoester reacts with methyl propiolate to give a Michael adduct which serves as a precursor for indolizine derivatives. Dimethyl acetylenedicarboxylate leads to isomeric adducts with different E/Z configuration depending on conditions117 (equation 81). 

A similar mercaptoacetate addition reaction to 5-acyl-4,7-dioxo-4,7-dihydrobenzo[i]thiophene-2-carboxylates followed by cyclization and oxidation to give benzo[ 1,2-6 5,4-ft ]dithiophene-4,8-dione derivatives 29 has been shown <03H1689>. Nitrogen bridged heterocycles, 3-(benzylthio)thieno[3,4-6]indolizine derivatives 30 have been synthesized and intramolecular arene-arene interactions within these compounds were reported <03CPB75>. The arene-arene interaction leads to significant shifts in the proton NMR signals and red shifts in the absorption maxima. 

Jorgensen, A. S., Jacobsen, P., Christiansen, L. B., Bury, P. S., Kanstrup, A., Thorpe, S. M., Naerum, L., Wasser-mann, K. Synthesis and Estrogen Receptor Binding Affinities of Novel Pyrrolo[2,1,5-cd]indolizine Derivatives. Bioorg. Med. Chem. Lett. 2000, 10, 2383-2386. 

The initial attack in the anodic oxidation of papaverine [75] probably involves a similar attack further oxidation and dimerization leads to the isolated product, 12,12 -bis-(2,3,9,10-tetramethoxyindolo[2,l-fl]isoquinolyl). An analogous reaction is the electrooxidation of a tetramethoxy-substituted 2-methyl-l-phenethyl-l,2,3,4-tetrahydroisoquinoline to a dibenzoquinolizinium derivative [76] and the oxidation of A,A -triphenyl-( -phenyle-nediamine to 9,10-diphenylphenazine [77]. Intramolecular Michel addition of nitrogen in a tetrahydroquinoline derivative to an o-quinone moity have resulted in the formation of a 5,6-dihydrodibenz[6,d]indolizine derivative [78]. A similar ring closure occurs during the oxidation of various catecholamines [79] and similar compounds [79] to indoles. Cyclic a-carbonylazo compounds, generated by anodic oxidation of the hydrazines, may be trapped by reaction with dienes to the expected heterocycles [80]. 

Intramolecular aliphatic C—H insertion is synthetically impractical with piperidine derivatives. However, formal insertion into the C—H bond of the pyrrole ring is of synthetic utility with indolizine derivatives. The copper-catalyzed pyrolysis of 170 (R = R = R = H) quantitatively gives indolizi-none 171 (R = R = R = H). The insertion of a strongly electrophilic... 

Pohjala, E. Indolizine derivatives. IV. Evidence for a disproportionation-dehydrogenation mechanism in the Perkin reaction of 2-pyridinecarbaldehyde in the presence of a,P-unsaturated carbonyl compounds to give 1-acylpyrrolo[2,1,5-cd]indolizines. Heterocycles 1975,3, 615-618. 

Photolytic, thermal or ultrasonicated reaction of a series of 3-arylmethyl-3-chloro-3//-diazirines with 2-vinylpyridine did not afford the expected l-arylmethyl-l-chloro-2-(2-pyridyl)cyclo-propanes. Instead, indolizine derivatives were produced via the corresponding A-ylides from arylmethylchlorocarbenes and 2-vinylpyridine. ... 

Indolizine derivatives were also made with good enantioselectivity by rearrangement and cyclization of spiro[cyclopropane-l,5 (4 7/)-isoxazoles], e.g. 50.The latter were prepared by condensation of 4-chloro-l-nitroalkanes with methylenecyclopropane and pyrolyzed by refluxing in dimethylformamide containing potassium carbonate. 

Treatment of A -(4-nitrophenyl)cyclopropenimines with pyridine at 0°C gave 3-(4-nitrophen-ylamino)indolizine derivatives... 

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