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Modification of the quinolizine backbone of the alkaloid lupinine was carried out by introducing substituted 1,2,3-triazole. When NaN3 acts upon the product of the reaction of lupinine with methanesulfonyl chloride, lupinyl azide is formed which in the reaction with terminal alkynes in the presence of aqueous CuSO4 and sodium ascorbate forms the corresponding (1S,9aR)-1-[(1,2,3-triazol-1-yl)-methyl]octahydro-1H-quinolizines with various substituents at the C-4 position of the triazole ring. The structures of lupinine methanesulfonate and 1-[(1,2,3-triazol-1-yl)methyl]octahydroquinolizines were confirmed by X-ray structural analysis. 1-[(1,2,3-Triazol-1-yl)methyl]octahydroquinolizines containing a hydroxymethyl or 2-hydroxypropan-2-yl substituent at the C-4 position of the triazole ring exhibit pronounced analgesic activity.

Iridium(I) N-heterocyclic carbene complexes of formula Ir(κ2O,O’-BHetA)(IPr)(η2-coe) [BHetA=bis-heteroatomic acidato, acetylacetonate or acetate; IPr=1,3-bis(2,6-diisopropylphenyl)imidazolin-2-carbene; coe=cyclooctene] have been prepared by treating Ir(κ2O,O’-BHetA)(η2-coe)2 complexes with IPr. These complexes react with 2-vinylpyridine to afford the hydrido-iridium(III)-alkenyl cyclometalated derivatives IrH(κ2O,O’-BHetA)(κ2N,C-C7H6N)(IPr) through the iridium(I) intermediate Ir(κ2O,O’-BHetA)(IPr)(η2-C7H7N). The cyclometalated IrH(κ2O,O’-acac)(κ2N,C–C7H6N)(IPr) complex efficiently catalyzes the hydroalkenylation of aromatic and aliphatic terminal alkynes and enynes with 2-vinylpyridine to afford 2-(4R-butadienyl)pyridines with Z,E configuration as the major reaction products (yield up to 89 %). In addition, unprecedented (Z)-2-butadienyl-5R-pyridine derivatives have been obtained as minor reaction products (yield up to 21 %) from the elusive 1Z,3gem-butadienyl hydroalkenylation products. These compounds undergo a thermal 6π-electrocyclization to afford bicyclic 4H-quinolizine derivatives that, under catalytic reaction conditions, tautomerize to 6H-quinolizine to afford the (Z)-2-(butadienyl)-5R-pyridine by a retro-electrocyclization reaction., Financial support from the Spanish Ministerio de Ciencia e Innovación (MICINN/FEDER) under Project PID2019-103965GB-I00, and the Departamento de Ciencia, Universidad y Sociedad del Conocimiento del Gobierno de Aragón (group E42_20R) is gratefully acknowledged. I.G. thanks the Humboldt Foundation for a research fellowship.

Here we report the 1,3-dipolar cycloaddition of polycyclic aromatic azomethine ylides with nitriles to produce highly fused imidazole derivatives, that is, tribenzo[b,g,ij]imidazo[2,1,5-de]quinolizine. The advantages of this transformation are the broad substrate scope and the good functional group compatibility. The subsequent palladium-catalyzed intramolecular cyclization provides an efficient approach to further π-extended imidazoles, that is, 14b1,15-diazadibenzo[fg,ij]cyclopenta[rst]pentaphene.

A Cu(OAc)2-catalyzed domino tricyclization between naphthalene-1,8-diamine and 2-(phenylethynyl)benzaldehyde is described, enabling aerobic oxidative dehydrogenation coupling to access heptacyclic quinolizino[3,4,5,6-kla]perimidines. In this reaction, the formation of three new rings and four new bonds was achieved in a functional-group-compatible fashion, allowing a facile method toward fused aza-heterocycles containing both quinolizine and perimidine moieties.

A facile synthetic method for the construction of 2-substituted-4-oxo-4H-quinolizine-based core structure has been successfully developed. The synthesis made use of a one-pot Stobbe condensation followed by cyclization starting from the commercially available 2-pyridinecarbaldehyde. The structure of the formed 4-oxo-4H-quinolizine-2-carboxylate was fully confirmed by mass spectra, 1H NMR and 13C NMR, correlation spectrography, heteronuclear multiple bond correlation, and heteronuclear single quantum coherence (HSQC) spectra. The ethyl carboxylate moiety was then further functionalized via direct aminolysis by a range of amines to afford the corresponding 4-oxo-4H-quinolizine-2-carboxamides 4a–i in moderate to good yields.

Pyridines were found to be a convenient nucleophile in the copper(I)-catalyzed synthesis of N-tosyl-4-iminoquinolizines from 2-pyridyl compounds. Intramolecular cyclization of an in situ generated ketenimine and a tethered pyridine, followed by a base-promoted oxidation, affords the desired products in moderate to good yields under mild reaction conditions.

The cerium(IV) ammonium nitrate (CAN)-catalyzed sequential multicomponent reaction between tryptamine, α,β-unsaturated aldehydes, and β-dicarbonyl compounds affords highly substituted indolo[2,3-a]quinolizines in a single synthetic operation. Two rings are generated through the creation of two C-C and two C-N bonds by a domino process comprising initial β-enaminone formation, followed by individual Michael addition, 6-exo-trig cyclization, iminium formation, and Pictet-Spengler steps. Furthermore, the reaction is diastereoselective and affords exclusively compounds with a trans relationship between the H-2 and H-12b protons. The use of amines bearing a less nucleophilic side chain aromatic ring (5-bromotryptamine, 3,4-dimethoxyphenylethylamine) prevents the Pictet-Spengler final step and leads to N-indolylethyl or N-phenylethyl-1,4-dihydropyridines, which are cyclized to the corresponding indolo[2,3-a]quinolizines or benzo[a]quinolizines in the presence of HCl in methanol/water. Treatment of the fused quinolizine derivatives with sodium triacetoxyborohydride led to the corresponding indolo[2,3-a]quinolizidines or benzo[a]quinolizidines, possessing four stereogenic centers, as mixtures of two diastereomers.

The cascade oxidative annulation reactions of aryl imidazoles with two molecules of alkynes via multiple C–H activation proceed efficiently in the presence of [Cp*RhCl2]2 and Cu(OAc)2·H2O to give substituted benzo[ij]imidazo[2,1,5-de]quinolizine-based polyheteroaromatic compounds. This method is compatible with various functional groups, which are very useful for further synthetic transformations.

The three-component reactions (TCRs) involving quinoline or isoquinoline, dialkyl acetylenedicarboxylate and β-trifluoroacetyl vinyl ethyl ether were investigated. The reaction proceeded smoothly under ambient temperature in DMSO to give the 4-trifluoroacetyl substituted benzo[c]quinolizine derivatives in moderate yields. However, under the same reaction condition, isoquinoline afforded the 2-trifluoromethyl substituted 1-oxa-(11H)-benzo[a]dihydroquinolizine or 4-trifluoroacetyl substituted benzo[a]dihydroquinolizine products. The possible reaction pathways were proposed.

Ionic liquids were found to be a suitable reaction medium for 1,4-dipolar cycloaddition reactions of an isoquinoline, an activated alkyne, and a 4-oxo-4H-1-benzopyran-3-carboxaldehyde at room temperature to afford [1]benzopyrano-pyrido-isoquinoline (=9aH,15H-benzo[a][1]benzopyrano[2,3-h]quinolizine) derivatives selectively in good yields. The ionic liquid can be recovered and recycled in further runs without loss of activity.

The condensation between 2-(2-oxocyclohexyl)propionic acid and β-arylethylamines, followed by dehydrogenation leads to 1-β-arylethylcarbostyrils in high yields, thus facilitating the Bishler-Napieralski pathway to dibenzo[a,f]quinolizines. An illustration is presented with the synthesis of 6,7,12,13-tetrahydro-9,10-dimethoxy-11bH-dibenz[a, f]quinolizine and 6,7,12,12b,13,14-hexahydrobenz[f]indolo[2,3-a]quinolizine. The octahydro-2-quinolone derivatives could not be reduced to the perhydro compounds, but resulted in a cyclised compound.

Cyclopenta[a]quinolizine, a novel tricyclic pseudoazulene, was prepared by reaction of cyclopentadienyllithium with oxazolo[3,2-a]pyridinium or substituted pyridinium salts. Structural analysis (X-ray analysis, NMR and UV spectroscopy) and DFT calculations confirm its highly dipolar nature (due to delocalization of the negative charge around the five-membered ring) combined with partial localization of bonds in both six-membered rings.

Polycyclic quinolizine derivatives, quinolizino[3,2-α]quinolizines (4a-c), were synthesized in moderate yields by a one-pot method using ketene dithioacetal, methyl bis(methylsulfanyl)methylene-cyanoacetate (2), alkyl 2-pyridylacetates (1a, b), and 2-pyridylacetonitrile (1c). Compounds 4a, b exhibited red fluorescence (Em max: 576 nm) in solid state., HETEROCYCLES, 78(5), pp.1271-1279; 2009

New fluorescent compounds 1,11-dihydro-11-imino-1-oxo-3-phenylpyrano[4,3-b]quinolizines were synthesized in good yields by the reaction of 6-aryl-3-cyano-4-methylsulfanyl-2H-pyrones and 4-methylsulfanyl-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-carbonitrile with 2-pyridylacetates. These fused quinolizine derivatives exhibited fluorescence in solid and solution states.

The synthesis of 2,3,4,4a,5,6-hexahydro-6H-spiro[benzo[c]quinolizine-5,4′-pyrazol]-5′-ones has been achieved by the reaction of 2-piperidinobenzaldehydes with 2-aryl-5-methyl-2,4-dihydropyrazol-3-one via the “tert-amino effect” mechanism.

While 3-aryl-2-ketopropanols (X) exclusively give the pyrandiones (XI), 3-pyridyl derivatives give either pyrandiones (VII) and (IX) or pyranoquinolizinetriones (III) and (V) depending on the substitution pattern at the pyridine moiety.

Keywords Reactions of 1-cyano-4-oxo-4H-quinolizine-3-diazonium tetrafluoroborate (1a) and 4-oxo-4Hpyridino[ 1,2-a]pyrimidine-3-diazonium tetrafluoroborate (1b) with aliphatic amines 2a - g were studied. Treatment of heteroaryldiazonium salts 1 with secondary amines 2a - d afforded the corresponding N-alkyl-N’-heteroaryltriazenes 3a - h in high yields. On the other hand, reactions of 1a with aliphatic primary amines 2e - g resulted in an unexpected rearrangements into the corresponding picolinic acid N-alkylcarboxamides 4a - c.

A convenient ipso substitution method for the preparation of benzo[c]quinolizine (2) and 4-hydroxy-3-(2'-pyridyl)coumarin (3) has been developed. The intramolecular nucleophilic substitution reaction of 3-oxo-2-(2'-pyridyl)-(2-halophenyl)propanoate (1) in refluxing xylenes gives initially benzo[c]quinolizine, while further heating results in the formation of 4-hydroxycoumarin. A mechanism has been proposed to rationalize the two competitive reaction pathways, and the role of HCl is discussed. Under optimized conditions, seven benzo[c]quinolizines and five coumarins were prepared in moderate to good yields.

Tetrahydro-1H,7H-benzo[ij]quinolizine-1,7-diones have been obtained by the cyclization of N-alkoxyphenyl-N-(2-carboxyethyl)-β-alanines. Fission of the ester bond occurs on cyclization of N-(4-ethoxyphenyl)-N-(2-carboxyethyl)-β-alanine, but the cyclization of the 3,4-dialkoxyphenyl derivative leads to the formation of 9-alkoxy-8-hydroxy-2,3,5,7-tetrahydro-1H,7H-benzo[ij]quinolizine-1,7-diones. The corresponding dioximes and diphenylhydrazones were obtained.

The dehydrogenative coupling of imidazo[1,2-a]pyridine derivative has been achieved for the first time. In cases in which the most-electron-rich position of the electron-excessive heterocycle was blocked by a naphthalen-1-yl substituent, neither oxidative aromatic coupling nor reaction under Scholl conditions enabled the fusion of the rings. The only method that converted the substrate into the corresponding imidazo[5,1,2-de]naphtho[1,8-ab]quinolizine was coupling in the presence of potassium in anhydrous toluene. Moreover, we discovered new, excellent conditions for this anion-radical coupling reaction, which employed dry O2 from the start in the reaction mixture. This method afforded vertically fused imidazo[1,2-a]pyridine in 63 % yield. Interestingly, whereas the fluorescence quantum yield (Φfl) of compound 3, despite the freedom of rotation, was close to 50 %, the Φfl value of flat naphthalene-imidazo[1,2-a]pyridine was only 5 %. Detailed analysis of this compound by using DFT calculations and a low-temperature Shpol′skii matrix revealed phosphorescence emission, thus indicating that efficient intersystem-crossing from the lowest-excited S1 level to the triplet manifold was the competing process with fluorescence. Po raz pierwszy otrzymano nowy typ związku heterocyklicznego - imidazo[1,2-a]pirydyne sprzezoną w pozycjach 3 i 5 z naftalenem. Udowodniono, ze spośrod wszystkich metod wewnątrzcząsteczkowego odwodornienia tylko sprzeganie z wytworzeniem aniono-rodnikow prowadzi do oczekiwanego produktu. Opracowano przy tym nowe warunki prowadzenia tej reakcji, w ktorych suchy tlen jest obecny od początku w ukladzie reakcyjnym. Dokladne zbadanie wlaściwości optyczne obu związkow zarowno w roztworze jak i w matrycach Szpolskiego oraz poprzez obliczenia kwantowo-mechaniczne wykazaly, ze za niską wydajnośc kwantową fluorescencji odpowiedzialne jest przejście miedzysystemowe na nisko lezący stan trypletowy.

The cerium(IV) ammonium nitrate (CAN)-catalyzed sequential multicomponent reaction between tryptamine, α,β-unsaturated aldehydes, and β-dicarbonyl compounds affords highly substituted indolo[2,3-a]quinolizines in a single synthetic operation. Two rings are generated through the creation of two CC and two CN bonds by a domino process comprising initial β-enaminone formation, followed by individual Michael addition, 6-exo-trig cyclization, iminium formation, and Pictet–Spengler steps. Furthermore, the reaction is diastereoselective and affords exclusively compounds with a trans relationship between the H-2 and H-12b protons. The use of amines bearing a less nucleophilic side chain aromatic ring (5-bromotryptamine, 3,4-dimethoxyphenylethylamine) prevents the Pictet–Spengler final step and leads to N-indolylethyl or N-phenylethyl-1,4-dihydropyridines, which are cyclized to the corresponding indolo[2,3-a]quinolizines or benzo[a]quinolizines in the presence of HCl in methanol/water. Treatment of the fused quinolizine derivatives with sodium triacetoxyborohydride led to the corresponding indolo[2,3-a]quinolizidines or benzo[a]quinolizidines, possessing four stereogenic centers, as mixtures of two diastereomers.

Access to the tricyclic benzo[a]quinolizine ring system, which forms the characteristic framework of alkaloids of the berberine and emetine type, is readily obtained by a three-step reaction sequence. This sequence includes the formation of a Schiff base, derived from a 2-bromo-substituted phenylethylamine, and its tandem Mannich/conjugate addition reaction with an electron-rich silyloxy diene forming an intermediate enaminone, which subsequently undergoes a Heck-type cyclization. Highest yields of the tandem Mannich/conjugate addition for aromatic Schiff bases and formaldehyde imines are observed in the presence of ZnCl2 in THF, whereas aromatic imines give the best results in the presence of EtAlCl2 in CH2Cl2. The best results for the Heck-type cyclizations are obtained either under heterogeneous conditions in the presence of K2CO3/NEt4Cl at 120 °C in DMF or in refluxing toluene or under homogeneous conditions at 100 °C in DMF in the presence of NEt(i-Pr)2. Depending on the substitution pattern of the d...

Preparation and structure of 1,2,3-triazolo[1,5-a]pyridinium N2-dicyanomethylides 7a,b are described. Reaction with methyl propiolate gives trisubstituted indolizines 8a,b in good yield. Reaction of 7b with dimethyl acetylenedicarboxylate gives a quinolizine 12.

The reactions of diethyl N,N-dimethylaminomethylenemalonate (3) with N- and C- nucleophiles were studied. In the reaction of 3 with heterocyclic amines 4, with the amino group attached at α-position in respect to the ring nitrogen atom, substitution of the dimethylamino group in 3 with the heterocyclic amino took place to give diethyl heteroarylaminomethylenemalonates 5, which can cyclize into fused azino- 6 or azolopyrimidinones 7. In the reaction of 3 with the compound with an active methylene group attached at α-position in regard to the ring nitrogen atom, such as pyridinylacetonitrile (8), ethyl pyridinyl- (9), and quinolinylacetate (10), fused quinolizines 11 and 12, and benzo[c]quinolizine 13 were formed, respectively. Heterocyclic systems with an active or potentially active methylene group incorporated in the ring system, such as pyrazole 14, pyrimidine 15, and pyridine derivative 18, gave with 3 fused pyranones 16, 17, and 19, and dihydroxynaphthalenes 22 and 23 naphtho[2,1-b]pyranones 24 and 25.

A new access to the indolo[2,3-a]quinolizine ring system was devised using the thermal decarboxylative ring-opening of 3-carboxyl isoxazoles into α-cyano aldehydes. Thus, from acetal 8b the indolo[2,3-a]quinolizine 5 was obtained in four steps via the β-carboline 11 which on heating gave compound 5 .

A new approach (AB + D → ABCD) to the construction of tetracyclic 8-azagonane (cyclopenta[5,6]pyrido[2,1-a]isoquinoline or benzo[a]cyclopenta[f]quinolizine) structures was developed and exemplified by cyclocondensation of 1-alkyl-3,4-dihydroisoquinolines with ethyl 2-oxocyclopentanecarboxylate.

Forging the lock that autolocks! Rh-NHC catalysts promote a new access to 4 H-quinolizine species from 2-vinylpyridine and terminal and internal alkynes through C-H activation and C-C coupling reactions (see figure). N-Bridgehead heterocycle formation is favored for internal- over terminal-substituted butadienylpyridine derivatives in a thermal 6π-electrocyclization process. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim., Financial support from the Ministerio de Economía y Competitividad of Spain Project CTQ2010–15221), the Diputación General de Aragón (E07), the ARAID Foundation under the program “Jóvenes Investigadores”, and CONSOLIDER INGENIO-2010, under the Project MULTICAT (CSD2009–00050) are gratefully acknowledged.

In the reaction of 2-(2-pyridylcarbonyl)benzoyl chloride, which exists in the form of 6,11-dioxo-6,11dihydrobenzo[b]quinolizinium chloride, with p-nitroaniline, 2-(4-nitrophenylimino)-6, 11-dihydro-2H-benzo-[b]quinolizine-6, I I -dione is unexpectedly formed. When it reacts with water or methanol there is an opening of the quinolizine ring and aromatization of the quinoid fragment with the formation of 2-[4-(4nitrophenylamino)-2-pyridylcarbonyl]benzoic acid or its methyl ester. Under the action of antimony pentachloride, 2- 2-quinolylcarbonyl)benzoylchloride-3 (2-quinolyl)-3-chloro- 1, 3-dihydrobenzo[c]furan-1 -one -is converted to 3-(2-quinolyl)-1,3-dihydrobenzo[c]furan-1-on-3-ylium hexachlorantimonate, which undergoes isomerizing recyclization upon heating to 7,12-dioxo-7,12-dihydrobenzo[b/ hexachloroantimonate. The latter enters into an analogous reaction with p-nitroaniline, thereby forming 5-(4-nitrophenylimino)-7,12-dihydro-5H-dibenzo[b,f]quinolizine-7,2-dione.

Crystals of the title compound, C(23)H(17)ClN(4)O(2).2.5H(2)O, contain channels filled with highly disordered water molecules. The best structure refinement was obtained by removing the solvent contribution from the intensity data and refining against a solvent-free model. The central six-membered ring of the quinolizine molecule has a slightly distorted screw-boat conformation.

In the title compound, C20H15NO, the heterotricycle is essential planar [maximum deviation = 0.0790 (5) Å] and makes a dihedral angle of 50.70 (2)° with the benzene ring. The formyl group is almost coplanar with the tricyclic ring, the C—C—C—O torsion angle being −0.78 (13)°.

Photolysis of 1-( chloroacetyl )-8,9-dimethoxy-2,3,5,6-tetrahydropyrrolo[2,1-a] isoquinoline (4a) and 1-( chloroacetyl )-9,10-dimethoxy-3,4,6,7-tetrahydro-2H-benzo[a] quinolizine (4b) in acidified water/ acetonitrile each gave mixtures of two products: 10,11-dimethoxy-1,4,5,6,7,8-hexahydro-3,6-methano-2H-3-benzazecine-7,13-dione (5) plus crude 7,8-dimethoxy-1,2,4,5,9,10-hexahydrobenzo [de] pyrrolo [3,2,1-ij] isoquinoline-9,10-dione (6); and 12-hydroxy-11-methoxy- 1,2,4,5,6,7,8,9-octahydro-3,7-methano-3-benzazacycloundecine-8,14-dione (7) and 8,9-dimethoxy-2,3,5,6,10,11-hexahydro-1H-benzo[de] pyrido [3,2,1ij ]quinoline-10,11-dione (8), respectively. The structures of (5), (7) and (8) were confirmed by X-ray crystallographic studies.

The reactions of diethyl N,N-dimethylaminomethylenemalonate (3) with N- and C- nucleophiles were studied. In the reaction of 3 with heterocyclic amines 4, with the amino group attached at α-position in respect to the ring nitrogen atom, substitution of the dimethylamino group in 3 with the heterocyclic amino took place to give diethyl heteroarylaminomethylenemalonates 5, which can cyclize into fused azino- 6 or azolopyrimidinones 7. In the reaction of 3 with the compound with an active methylene group attached at α-position in regard to the ring nitrogen atom, such as pyridinylacetonitrile (8), ethyl pyridinyl- (9), and quinolinylacetate (10), fused quinolizines 11 and 12, and benzo[c]quinolizine 13 were formed, respectively. Heterocyclic systems with an active or potentially active methylene group incorporated in the ring system, such as pyrazole 14, pyrimidine 15, and pyridine derivative 18, gave with 3 fused pyranones 16, 17, and 19, and dihydroxynaphthalenes 22 and 23 naphtho[2,1-b]pyranones 24 and 25.

Access to the tricyclic benzo[a]quinolizine ring system, which forms the characteristic framework of alkaloids of the berberine and emetine type, is readily obtained by a three-step reaction sequence. This sequence includes the formation of a Schiff base, derived from a 2-bromo-substituted phenylethylamine, and its tandem Mannich/conjugate addition reaction with an electron-rich silyloxy diene forming an intermediate enaminone, which subsequently undergoes a Heck-type cyclization. Highest yields of the tandem Mannich/conjugate addition for aromatic Schiff bases and formaldehyde imines are observed in the presence of ZnCl2 in THF, whereas aromatic imines give the best results in the presence of EtAlCl2 in CH2Cl2. The best results for the Heck-type cyclizations are obtained either under heterogeneous conditions in the presence of K2CO3/NEt4Cl at 120 °C in DMF or in refluxing toluene or under homogeneous conditions at 100 °C in DMF in the presence of NEt(i-Pr)2. Depending on the substitution pattern of the d...

The quaternizations of dibenzoquinolizines 9 and 14 with 3-halo-1-propanols are highly cis-selective (94-100% cis), results consistent with the N-methylation of O-methylcapaurine (7b), but in contrast to the proposed trans-stereochemistry of dibenzo[a,h]quinolizine methiodide 10 and the analogous quaternizations of 1-benzyl- and 1-phenylisoquinoline congeners 5b and 5c. In this report, we describe stereoselective preparation of the unique cis-dibenzoquinolizinium propanols 15 and 16and their transformation into bis- and mixed-onium chlorofumarates 19, 20ab, and 26. Dibenzo[a,g]quinolizinium propanol 15 was prepared enantioselectively in three steps from dihydroisoquinoline 11. Asymmetric transfer hydrogenation of 11 in the presence of triethylamine/formic acid and Noyori's chiral ruthenium catalyst 12 produced R-(-)-5',8-dimethoxynorlaudanosine (13) in 98% yield and 87% ee. Pictet-Spengler cyclization of 13 in formalin/formic acid afforded the dibenzo[a,g]quinolizine 14 in 65% yield. Quaternization of 14 with 3-chloro-1-propanol under Finkelstein conditions generated cis-dibenzoquinolizinium propanol 15 in 85% yield with >94% cis-selectivity. The cis-dibenzo[a,h]quinolizinium propanol 16 was obtained as a single stereoisomer by reaction of the known tetramethoxyquinolizine 9 with neat 3-iodo-1-propanol. Bis-onium chlorofumarates 18 and 19 and the mixed-onium derivative 20ab were prepared by a pool synthesis procedure from (1R)-trans-6a, 16, and chlorofumaryl chloride (17). Mixed-onium alpha-chlorofumarate 26 was synthesized from (1S)-trans-6d, 15 and (+/-)-trans-2,3-dichlorosuccinic anhydride (22), employing a recently disclosed chlorofumarate mixed-diester synthesis. The title compounds (19, 20ab, and 26) displayed curare-like effects of ultrashort duration in rhesus monkeys.

Novel synthetic routes to nitrogen-bridged derivatives of pyrrolo[2,1,5-cd]indolizine and pyrrolo[2,1,5-de]quinolizine were developed starting from 2-acyl-N-(acylmethyl)pyridinium halides. Thus, 2-benzoyl-N-phenacylpyridinium bromide (1) afforded 3,4-diphenylpyrrolo[2,1,5-cd]indolizines (4) via 1,3-dipolar cycloaddition, to yield 3,5-dibenzoylindolizines (3), followed by intramolecular McMurry coupling. Similarly, 2-(1,3-dioxolan-2-yl)-N-phenacylpyridinium bromide (5) gave 3-phenylpyrrolo[2,1,5-cd]indolizine (7) together with the unexpected product 3-phenyl-4-hydroxypyrrolo[2,1,5-cd]indolizines (8). However, 2-acetyl-N-phenacylpyridinium bromide (13) or 2-benzoyl-N-acetonylpyridinium bromide (16) underwent a tandem reaction of aldol condensation and 1,3-dipolar cycloaddition to form 3-phenyl-5H-pyrrolo[2,1,5-de]quinolizin-5-ones (15) or 5-phenyl-3H-pyrrolo[2,1,5-de]quinolizin-3-ones (17) in a single step. These novel procedures are general and can be carried out under convenient conditions.

The 1-substituted 3-amino-4H-quinolizin-4-ones 13, available in two steps from 10 and methyl (Z)-2-benzyloxycarbonylamino-3-(dimethylamino)propenoate (11), were diazotized to give the stable diazonium tetrafluoroborates 7a and 7b. Heating of these diazonium salts in alcohols gave mixtures of 3-unsubstituted quinolizine derivatives 8a and 8b and the alkyl indolizine-3-carboxylates 9a−h. The ratio of the two types of products 8 and 9 was dependent on the type of alcohol employed. Thus, treatment of 7a or 7b with 2-propanol predominantly resulted in the 3-unsubstituted quinolizinones 8, while treatment of 7a or 7b with primary alcohols gave the indolizine-3-carboxylates 9 as the major products in most cases. The transformation of the 4-oxoquinolizine-3-diazonium tetrafluoroborates 7a and 7b into the alkyl indolizine-3-carboxylates 9a−h represents the first example of a Wolff rearrangement in the fused cyclic α-diazoamide series.

A convenient ipso substitution method for the preparation of benzo[c]quinolizine (2) and 4-hydroxy-3-(2'-pyridyl)coumarin (3) has been developed. The intramolecular nucleophilic substitution reaction of 3-oxo-2-(2'-pyridyl)-(2-halophenyl)propanoate (1) in refluxing xylenes gives initially benzo[c]quinolizine, while further heating results in the formation of 4-hydroxycoumarin. A mechanism has been proposed to rationalize the two competitive reaction pathways, and the role of HCl is discussed. Under optimized conditions, seven benzo[c]quinolizines and five coumarins were prepared in moderate to good yields.

Reaction of phenyl vinyl ketone with cyclopentanone under thermal conditions resulted in novel domino products, 1,5,9-triketones along with the expected 1,5-diketones. The 1,5,9-triketones were formed via a Michael–Michael-rearrangement pathway. On the other hand, reaction under basic conditions furnished a spiro[4.5]decanone, formed by domino pathways involving Michael–Michael-aldol condensation reactions. Microwave mediated reductive amination–cyclization of the 1,5,9-triketone furnished the perhydrocyclopenta[ij]quinolizine derivative.

In the synthesis of 4H-quinolizine derivatives involving the use of a sulfonyl ketene dithioacetal, we found a novel reaction in which the remaining methylsulfanyl group was replaced with a proton after the ring-closure reaction in the quinolizine skeleton under mild conditions, without the use of any metallic reagent. The reaction of 3,3-bis(methylsulfanyl)-2-phenylsulfonylacrylonitriles (1a,b) with 2-pyridylacetonitrile (2a) in the presence of potassium carbonate as a base in DMSO afforded 4-imino-2-methylsulfanyl-3-phenylsulfonyl-4H-quinolizine-1-carbonitriles (3a,b). The methylsulfanyl group at the 2-position of 3a,b was readily removed under methanol reflux conditions to afford 4-imino-3-phenylsulfonyl-4H-quinolizine-1-carbonitriles (4a,b) in good yields. Alkyl 3-phenylsulfonyl-4H-quinolizine-1-carboxylates (4c–f) were directly synthesized from sulfonyl ketene dithioacetal (1a,b) with alkyl 2-pyridylacetates (2b,c) and involved desulfanylation by simple hydrolysis. In addition, the fluorescent properties of these compounds were investigated. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

In the title compound, C23H30N2O4·C2H6O, the indole derivative has four fused rings, forming an indolo[2-3a]quinolizine system, in which one six-membered ring is directly connected to the indole unit and has a distorted chair conformation. The fourth ring is also a six-membered ring, depicting a regular chair conformation. In the crystal, the molecules are linked by N—H...O and O—H...N interactions, forming aC(7) chain.

A short and efficient synthesis for a series of 1,6-diaryl- 3,4-diarylaminohexa-2,4-diene-1,6-diones was developed. Based on the acylation-prototropism sequence during the reaction of vari- ous aryl methyl ketones with bis-imidoyl chlorides, the products were isolated in good yields. Substituted acetophenones, acetyl- thiophene, 3-acetylpyridine, and acetylferrocene can be integrated into this reaction as ketone component. Similarly, a-tetralone can be transformed with bis-electrophiles into the corresponding bis- enaminones. Treatment of 2-acetylpyridine with N,N¢-bis(4- tolyl)ethanebis(imidoyl) dichloride yielded not only the expected bis-enaminone, but also a new quinolizine derivative which was structurally characterized by single crystal X-ray analysis. Analo- gously, pinacolone and cyclopropyl methyl ketone can readily be converted into bis-enaminones. Monoimidoyl chlorides showed the same reactivity, providing derivatives in high yields.

The 13C NMR spectra of 22 alkyl-substituted 9aH-quinolizine-1,2,3,4-tetracarboxylates have been obtained and X-ray analyses have been performed for three of them. The chemical shift differences between the parent 9aH-quinolizine and the methyl-substituted compounds can only be interpreted in terms of the usual α and β effects for 8-methyl-9aH-quinolizine. 6-, 7-, 9-, and 9a-methyl substituents cause not only a very large deshielding of the carbon at the position of substitution together with shielding changes at adjacent atoms, but also influence the shieldings of the other carbons in both rings of the compounds under study. The observed changes are interpreted in terms of steric hindrance between the methyl groups of ring B and the ester groups of ring A, and hyperconjugative effects introduced by the methyl groups.

Goal-directed search for long-wavelength fluorescent dyes is an important problem in the chemistry of polymethines [1]. One of the principal methods for solving this problem is to search for new heterocyclic rings or to modify known heterocyclic rings in order to construct polymethine dyes. We know that polymethine dyes, derivatives of julolidine (2,3,5,7,6,9-hexahydrobenzo[i,j]quinolizine), are characterized by rather intense long-wavelength absorption bands [2]. With the aim of obtaining new polymethine dyes that are analogs of julolidine dyes (8-hydroxyjulolidine derivatives), we have studied the reaction of self-condensation of 9-formyl-8hydroxyjulolidine 1, which was carried out according to the procedure in [3]. We found that when compound 1 was fused with excess p-toluenesulfonic acid, the pyronine 3 was formed rather than the expected dye 2 [2].