Indolizines reactions

Dieckmann reaction, 4, 471 Indolizidine alkaloids mass spectra, 4, 444 Indolizidine immonium salts reactions, 4, 462 Indolizi dines basicity, 4, 461 circular dichroism, 4, 450 dipole moments, 4, 450 IR spectra, 4, 449 reactivity, 4, 461 reviews, 4, 444 stereochemistry, 4, 444 synthesis, 4, 471-476 Indolizine, 1-acetoxy-synthesis, 4, 466 Indolizine, 8-acetoxy-hydrolysis, 4, 452 synthesis, 4, 466 Indolizine, I-acetyl-2-methyI-iodination, 4, 457 Indolizine, 3-acyloxy-cyclazine synthesis from, 4, 460 Indolizine, alkyl-UV spectra, 4, 449 Indolizine, amino-instability, 4, 455 synthesis, 4, 121 tautomerism, 4, 200, 452 Indolizine, 1-amino-tautomerism, 4, 38 Indolizine, 3-amino-synthesis, 4, 461, 470... 

Indolizine, 1 -cyano-2-(methylthio)-synthesis, 4, 465 Indolizine, 3,5-dialkyl-synthesis, 4, 475 Indolizine, dihydrosynthesis, 4, 467, 468 Indolizine, dimethyl-mass spectrometry, 4, 187 Indolizine, 1,2-dimethyl-oxidative dimerization, 4, 458 Indolizine, 2,6-dimethyl-cycloaddition reaction, 4, 460 reduction, 4, 459... 

Indolizine, hydroxy-conformations, 4, 451 GLC retention times, 4, 451 synthesis, 4, 121 tautomerism, 4, 198, 452 Indolizine, 2-hydroxy-synthesis, 4, 463 Indolizine, 8-hydroxy-conformation, 4, 452 Indolizine, 2-hydroxymethyl-synthesis, 4, 461 Indolizine, 3-hydroxymethyl-synthesis, 4, 461 Indolizine, 6-hydroxymethyl-synthesis, 4, 461 Indolizine, methyl-mass spectra, 4, 187, 450 NM 4, 448 Indolizine, 2-methyl-diazo coupling, 4, 454 mass spectra, 2, 529, 4, 450 nitration, 4, 50, 454 nitrosation, 4, 454 reaction with diaryl disulfide, 4, 460 reaction with nitroethane, 4, 460 Indolizine, 3-methyl-basicity, 4, 454 Indolizine, 5-methyl-acidity, 4, 461 synthesis, 4, 466 Indolizine, 6-methyl-mass spectra, 4, 450 Indolizine, l-methyl-2-phenyl-nitration, 4, 454 nitrosation, 4, 454, 455 Indolizine, 3-methyl-2-phenyl-reaction... 

Diels and Meyer found that the exothermic reaction obtained on dropping pyridine into dimethyl acetylenedicarboxylate in methanol gave a mixture of the indolizine (108) and a methoxymethylindolizine formulated as (109), and some dimethyl fumarate and dimethyl methoxyfumarate. Later workers - obtained only the methoxymethylindolizine in rather poor yield. The indolizine (108) has also been isolated from the products obtained when the addition reaction was carried out in ether, but in this case the course of the reaction was very susceptible to the presence of impurities in the ether, and the results indicated that ethanol was necessary as a reactant. ... 

Very few reactions of carbenes with heterocyclic systems containing more than one hetero atom have been studied. They are confined to variants of the Reimer-Tiemann formylation of thiazoles, pyra-zoles, iminazoles, and indolizines/ and ring expansion does not appear to have been observed. 

A study of the photochemical reactions of some ylides of compound 1 showed the expected fragmentation to give, from compound 258 for example, 3-methyl-triazolopyridine and the products 259 and 260 postulated as derived from a carhene intermediate (00MI2). Ester 261 gives a hydrazone, and ylide 262 an indolizine. Thermal reactions of ylides are in Section IV. I. 

With a change to non-polar solvent, the reaction of ylides 269 with alkynes and alkenes changed dramatically, as shown in Scheme 10. With DM AD in toluene the ylides give pyrazolopyridines 272 in good yield (91TL4977), and with methyl propiolate (MEP) give indolizines 273 (92H(33)203). The reaction with acrylates is much less clean, but the variety of products is said to be formed from a diazene intermediate, which splits to give a diradical (93H(35)851). 

Scheme 77 RRM reactions of enantiopure cycloheptenes leading to dihydrocuscohydrine (390) [161], anaferin dihydrochloride (393) [162], and indolizine 167B (397) [163]...

Although the exact mechanism of the Tschitschibabin cyclisation has not been elucidated, it is reasonable, as shown in Scheme 4, to assume a series of reversible steps from the vinylogous ylide (or methylide) to a methine and an enol-betaine intermediate and then finally an irreversible dehydration to the indolizine nucleus. The reaction might be related to the modern electrocyclic 1,5 dipolar cyclization. 

Reaction of the nitrone 4-184 with allenic esters 4-185 as described by Ishar and coworkers led to the benzo[b]indolizines 4-186, together with small quantities of 4-187 (<5%) (Scheme 4.40) [63]. The first transformation is a 1,3-dipolar cycloaddition this is followed by four further steps, including a [4+2] cycloaddition of an intermediate 1-aza-l,3-butadiene. 

Tominaga and coworkers have reported the formation of indolizine by the reaction of azomethine ylide with l-nitro-2-phenylthioethylene (Eq. 10.86).146... 

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... 

Jug and co-workers investigated the mechanism of cycloaddition reactions of indolizines to give substituted cycl[3,2,2]azines <1998JPO201>. Intermediates in this reaction are not isolated, giving evidence for a concerted [8+2] cycloaddition, which was consistent with results of previous theoretical calculations <1984CHEC(4)443>. Calculations were performed for a number of substituted ethenes <1998JPO201>. For methyl acrylate, acrylonitrile, and ethene, the concerted [8+2] mechanism seems favored. However, from both ab initio and semi-empirical calculations of transition states they concluded that reaction with nitroethene proceeded via a two-step intermolecular electrophilic addition/cyclization route, and dimethylaminoethene via an unprecedented two-step nucleophilic addition/cyclization mechanism (Equation 1). 

Thieno[2,3(3,2)-/]indolizines such as 50 undergo Diels-Alder reactions with diethyl azodicarboxylate (DEAD) to give the tetracyclic system 51 (Equation 6) <1995TL83>. 

Whereas reaction of the cyano-substituted indolizine 251 with a base results in the tf-fused product (Equation 34), the diester 255 reacts to give only the Afused product 256 <1987CL2043> (Equation 37). Similarly, when the acylindolizines 257 are prepared (Equation 38), very small amounts of the thienoindolizines are found in the product mixture. When such indolizines are substituted with both cyano and keto groups, treatment with a base gives a mixture of products resulting from reaction of the ester enolate with either of these electrophiles <1989BCJ119> (Equation 39). 

Thienoindolizines can be prepared by treatment of the alkenylindolizine 261 with bromine and a base, whereby bromination of the indolizine ring also occurs. Alternatively, reaction of 261 with a tetraalkylammonium tribromide and a base gives the tricycle 262, which can then be brominated to 263 by treatment with molecular bromine <2004CPB279> (Scheme 71). 

The most frequently used synthetic route to cycl[3.2.2]azines involves the reaction of an indolizine with a dienophile, for example, DMAD, in the presence of a dehydrogenating agent such as palladium-on-carbon (Scheme 85), although the scope of the reaction is limited by the presence of substituents in one or both of the reactants, and/or the reaction conditions. If C-3 and C-5 of the indolizine are unsubstituted, the cyclazine is the main product a 3,4-dihydrocyclazine may sometimes be isolated as a by-product (see below). 

Reactions of 3-cyanoindolizines (indolizine-3-carbonitriles) with an excess of DMAD in the absence of palladium-on-carbon lead, not to cyclazines, but to 1 2 adducts, possibly 348, which are not isolable but undergo a series of rearrangements, giving finally 3-styrylpyrroles of the type 349 <1992J(P1)2437> (Scheme 87). 

The reaction of 6-methyl-7-nitro-2-phenylindolizine with DMAD gives, not only the expected nitrocyclazine but the denitrocyclazine as the main product the latter is formed, presumably, by loss of HNOz from the primary cycloadduct <1997RCB609>. Also reaction of the same indolizine with the ynamine 350 gives, not the... 

A third method for the synthesis of cycl[3.2.2]azines, from iV-(aroylmethyl)pyridinium salts via indolizines, involves intramolecular (reductive) McMurry coupling of the latter. For example, 3,5-dibenzoylindolizines, obtained from 2-benzoyl-iV-phenacylpyridinium bromide as shown (Scheme 91), are cyclized using zinc and titanium(iv) chloride to give the 3,4-diphenylcyclazines 352 in high yield (>90%). The reaction cannot be applied, however, to... 

Pyrano[3,2 ]indolizines such as 120 can be prepared from the reaction of N-( 1 -benzotriazolylmethyl)indolines with 3,4-dihydro-2//-pyran under acidic or Lewis-acidic conditions (Equation 26) <2001T4933>, and a simpler analogue 122 is the end product of an annulation process starting from the enamine 121 and ethyl acrylate <1996H(43)1391> (Scheme 34). Pyrano[4,3-/]indolizinetriones, for example, 124, result from the hydrolysis of protected 2,3-dihydro-l//-indolizincdioncs 123 (Equation 27) <2000H(53)771>. 

The reaction of 196 with phenyl chlorocarbene 198 illustrates the synthesis of indolizines by cyclization of pyridinium ylides (Scheme 7). Cyclization of ylide rotamer 199 generates the intermediate product 200, which undergoes elimination of chloride to provide compound 201 <2005EJ01532>. 

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