4//-Quinolizine, structure

Following the original pattern of synthesis worked out by Diels and Pistor 25 and with a view to verifying the structures of some of the oxidation and hydrolysis products, Acheson and Taylor26 have re-centlysynthesized 9-methyl-and 7,9-dimethyl-4/f-quinolizine-1,2,3,4-tetracarboxylic esters. On the bases of extensive oxidation and reduction studies and ultraviolet and N.M.R. spectral data, the different labile and stable adducts have been assigned the 9aH- (16, 17) or the 4//-quinolizine structures (18, 19). 

The 9ai7-quinolizine structure (82) for the labile adduct from 3,5-dimethylpyridine was clearly established by the nuclear magnetic resonance studies of Richards and Higham, and subsequent work showed the labile adduct from 3-methylpyridine was analogous. As the labile adducts from all the pyridines and benzopyridines so far examined have very similar infrared absorption spectra in the 5-7 yn. (carbonyl and aromatic) region and within quite close limits very similar ultraviolet absorption spectra, it can be concluded that all are derivatives of 9aH-quinolizine,... 

Synthesis of (—)-Lasubine II. A reductive desulfonylation with lithium in ammonia is employed in the total synthesis of quinolizidine alkaloid (—)-lasubine II.264 A conjugate addition of methyl (.S )-(2-pipcridyl)acetate to an acetylenic sulfone, followed by lithium diisopropylamide (LDA)-promoted intramolecular acylation is the key step in the preparation of the quinolizine structure of (—)-lasubine II (Eq. 154). 

The simplest member of the indolo[2,3-a]quinolizine alkaloid group has been found in Dracontomelum magniferum Bl. (II) it possesses structure (—)-l. No name has as yet been given for this levorotatory alkaloid. 

Two new zwitterionic alkaloids with a 5,6-dihydroindolo[2,3-a]quinolizine ring system have been isolated from Vinca major L. var. elegantissima Hort (13). The structures of vincarpine (4) and dihydrovincarpine (5) have been determined on the basis of their spectral data and via some derivatives obtained by either catalytic or hydride reduction. Interestingly, the H-NMR spectrum of vincarpine in TFA solution corresponds to structure 6 derived by lactonization of 4 in the presence of acid. 

Formation of the imine and subsequent reduction can often be achieved in one pot . Thus, a microwave-assisted reductive amination-cyclisation domino reaction was used as the key step in the synthesis of perhydrocyclo-penta[ij]quinolizines from 1,5,9-triketones. This type of heterocycle is an important structural element in a series of alkaloids. The reaction of the triketone with ammonium formate in PEG-200 was performed within 1 min using microwave irradiation of370 W in a domestic microwave oven. Amixture oftwo ofthree possible stereoisomers was obtained in 87% overall yield (Scheme 4.29)52. 

No formation of the diazacycl[3,2,2]azine system (138) was reported. During attempts to prepare the cycl[4,3,2]azine system (139) by reaction of the enamine (140) with DMAD, the cyclopenta[c]quinolizine (141) was formed.165 Two intermediates of suggested structures 142... 

If methanol is employed as reaction medium, quinolizines (e.g., 306) are not formed but relatively high yields of deep red 1 3-molar adducts from the quinoline and DMAD are obtainable.379 Two isomeric types of adducts are formed, which are called first and second red adducts because of their elution order on chromatography. These adducts proved extremely difficult to separate completely. A provisional structure (317), for which many geometrical isomers are possible, was put forward379 to account for the properties of the compounds, but an X-ray diffraction study has now shown that the... 

Another peculiarity appears in the case of replacement by an NR group it can be introduced into the carbon skeleton in such a way that it links both ring systems. Structures of this type, e.g., indolizine (23),43 quinolizine (24),44 and some azapentalenes3 (such as 25),45 are pseudoazulenes, also,... 

Pyridine and its derivatives react with 1,3-pentadienes forming cyclic products. This type of cyclization was observed by the authors of 95JFC(72)49. They showed that in the reaction of (Z)-1,1,2,5,5,5-hexafluoro-4-phenyl-3-trifluoromethyl-1,3-pentadiene 117 with pyridine the products are [ S,9aR]- and [lS,9tfS]-3-fluoro-9<2-hydro-l,2-bis(trifluoro-methyl)-l-phenyl-4//-quinolizin-4-ones 118 and 119 with 54 and 21% yields, respectively. The structure of the compounds was confirmed by X-ray analysis. Similarly, the reaction of (Z)-l,l,2,5,5,5-hexafluoro-4-iodo-3-trifhioromethyl-l,3-pentadiene 120 with 4-substituted pyridines gives the derivative of 4//-quinolizin-4-one 121 with quinoline, the product is derivative 122. 

As in the earlier review1 this account will be restricted to the quinolizinium ion (1), the benzo[a]- (2), benzo [ft]- (3), and benzo[c]quinolizinium (4) ions, and to their derivatives. The quinolizones and compounds of similar structure (5) will be included, but the quinolizines (6 and 7) only where they appear as intermediates in synthesis or reaction. A number of trivial and unsystematic names have been used (pyridocolinium ion, dehydroquinolizinium ion for compound 1 acridizinium ion, 4u-azoniaanthracene for compound 3 phenanthridizinium ion for compounds 2 or 4), and numbering has also varied. Throughout this chapter the numbering will be as shown in formulas 1 to 4. 

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