Quinolizines nucleophilic

Furazano[3,4-d]pyrimidine, 7-amino-synthesis, 6, 729 UV spectra, 6, 713 Furazanopyrimidines amine synthesis from, 5, 591 synthesis, 6, 418 Furazano[3,4-d]pyrimidines nucleophilic attack, 6, 719 nucleophilic substitution, 6, 713 reduction, 6, 402 7-substituted reactions, 6, 722 Furazano[3,4-a]quinolizines synthesis, 6, 730... 

Enamine fragments present in quinolizine systems show their expected behavior as nucleophiles. For example, reaction of the indoloquinolizine derivative 78 with formaldehyde at room temperature afforded the unstable hydroxymethyl derivative 79, while reflux of 78 with formaldehyde under acidic conditions led to indole deprotection and allowed the isolation of the pentacyclic derivative 80 (Scheme 4) <2001TL7237>. 

An example of this displacement between a pyridine nitrogen atom and an aryl halide is shown in Scheme 21. When 2-pyridyl acetates 138 were C-acylated with 2-halobenzoyl chlorides, the enolized products 139 resulting from the reaction suffered an intramolecular nucleophilic attack of the pyridine nitrogen atom onto the ipso-position to give benzo[c]quinolizinium salts 140 as intermediates. Loss of HC1 gas from 140 afforded benzo[c]quinolizine derivatives 141 <2002JOC2082>. 

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... 

Several lupin alkaloids have been derived from the unsaturated quinalozidine 433, that was obtained in the treatment of amine 431 with ortho-quinone 432. This quinone behaves as a model of topaquinone, the cofactor of copper-containing amine oxidases. The cyclization step involved a nucleophilic attack of the piperidine nitrogen of 431 onto a side-chain aldehyde function that is unmasked by the oxidative deamination. Quinolizine 433, when treated with dehydropiperidine, gave the oxime ether 434 that, on ozonolysis followed by reduction, afforded sparteine 10, presumably via the bis(iminium) system 435 (Scheme 102) <1996JOC5581>. 

Ethoxy-l-azaquinolizinium tetrafluoroborate (245), prepared by the action of triethyl-oxonium tetrafluoroborate on l-azaquinolizin-2-one (238), undergoes nucleophilic displacement by m -nitrobenzoylhydrazine (Scheme 121) to afford a l-aza-2H-quinolizine derivative (246), useful as a dye intermediate (61LA(640)98). 

When the nitrogen atom of a pyridine is sufficiently nucleophilic, for example 3-cyano- (pK 1.45) but not 3-bromopyridine (pATa 0.9), attack occurs at the triple bond of the ester.238 The reaction can be very vigorous and, if carried out at - 60° in ether, pyridine itself appears to yield the zwitterion 1 which can be trapped by carbon dioxide. No direct physical evidence has been obtained for 1 and the first product detectable by low-temperature NMR measurements is the 9a//-quinolizine 5.239 Both geometrical forms of the betaine (2) have been isolated, and, at 0° in chloroform, decomposition to carbon dioxide, detected by its absorption at 2335 cm-1, and a red tar, occur rapidly. Treatment of the betaines with aqueous perchloric acid at its freezing point, however,... 

Phenanthridine with DMAD in dry methanol yields 471, but if water is present related compounds are also formed.439 In benzene the expected quinolizine 472 and also the oxazine 473 are obtained.440,441 Nucleophilic attack at the carbonyl group of DMAD is uncommon. 

The addition of the phthalimido anion to triesters of 2-phosphonopropenoic acid at room temperature gives an initial adduct, which is unexpectedly inert to benzaldehyde reaction but which adds to a second molecule of the phosphonic diester to form a second carbanion the latter undergoes an intramolecular WEH condensation to give the heterocyclic system 371 indolizine and quinolizine phosphonic diesters have been similarly obtained from maleimide, succinimide and glutarimide anions ". The ability of piperidine to add to the compounds 372 decreases in the order R R = (BuO)H (exothermic reaction) > (BuO)2 > (BuO)Me > Bu2 (the last requires heat) ". Ethenylphosphonic diamides (372 R = r2 = NR2) are unreactive to nucleophiles (by virtue of reduced electrophilic character at phosphorus and thus reduced electron attraction from the carbon-carbon double bond) but are reactive to electrophilic reagents. ... 

Intramolecular nucleophilic addition reactions of enamines to suitable electrophiles placed y to the enamine nitrogen atom afford quinolizine derivatives. Examples of this strategy (Schemes 50... 

The major adducts formed when phenanthridine is allowed to react with dimethyl acetylenedicarboxylate have been reformulated. - An initial Michael-type reaction gives the zwitterion (206) and succeeding reactions depend on the nature of the solvent. Adduct (207) is formed in anhydrous methanol by the addition of a proton and methoxide ion, while in benzene nucleophilic attack on the carbonyl group of a second ester molecule and subsequent cyclization provides 208. Alternatively, reaction at the triple bond of a second molecule of ester followed by ring closure of the new zwitterion gives 209. Other products related to 207 arise if the methanol contains water. 6-Methylphenanthridine with dimethyl acetylenedicarboxylate in benzene gives a mixture of the azepine (210) and tetramethyl 9a-methyl-9aA-dibenzo[a,c]quinolizine-6,7,8,9-tetracarboxylate. The... 

If halogen is present at the 4-position of the quinolizinium ion (e.g., 8), displacement reactions are possible. Thus, sodium malonic ester affords the methylene quinolizine 7 by nucleophilic substitution and subsequent deprotonation, whereas Pd-catalyzed... 

Interesting role of pyridine in dipolar cycloadditions was provided by Matsumoto [84]. High-pressure reaction of 2-halogenopyridines with dimethyl acetylene dicarboxylate provided 1 2 adducts 9aH-quinolizines 229 and 4H-quinolizines 230 (Scheme 55). The reaction mechanism includes [3 + 2] cycloaddition reaction in the first step nucleophilic attack of the nitrogen heterocycle form a 1,5-dipolar intermediate 228 which combines with the second molecule of the DM AD giving a cyclic product 229. In the case of fluorine substituent, 1 3 adduct of xmknown structure is formed in 5.3% yield. 

The enantioselective intramolecular formal 2+4-cycloaddition of acrylates and a, -unsaturated imines (99) catalysed by chiral phosphines (100), derived from amino acids, produced A-heterocycles (101) (Scheme 31). Chiral dirhodium(II) carboxamidates (102) catalysed the hetero-Diels-Alder reactions between 2-aza-3-silyloxy-l,3-butadienes and aldehydes to yield all cw-substituted l,3-oxazinan-4-ones in high yields and high enantioselectivity (98% ee)P The nickel-catalysed 4 + 2-cycloaddition of a, -unsaturated oximes with alkynes yielded 2,3,4,6-tetrasubstituted pyridine derivatives. The reaction of isoquinoline, an activated alkyne, and 4-oxo-4//-l-benzopyran-3-carboxaldehyde (103), in ionic solvents, produced 9a//,15//-benzo[a][l]benzopyrano[2,3-/t]quinolizine derivatives (105) via the zwitterion (104) selectively and in good yields (Scheme 32).The Diels-Alder cycloaddition of ethyl 3-(tetrazol-5-yl)-l,2-diaza-l,3-butadiene-l-carboxylates with -rich heterocycles, nucleophilic olefins, and cumulenes formed 3-tetrazolyl-l,4,5,6-tetrahydropyridazines regioselectively. The silver-catalysed formal inverse-electron-demand Diels-Alder... 

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