Quinolizines, acyl

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>. 

The quinolizine derivative 276 was obtained through a Friedel-Crafts acylation reaction onto the C-3 indole position of 275. This precursor was obtained by a sequence comprising a Fischer cyclization leading to 5-methyl-2-(2-pyridyl)indole 274, catalytic hydrogenation, N-alkylation with ethyl bromoacetate, and hydrolysis of the ester group (Scheme 59) <1999FA479>. 

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). 

Attempts to condense the quinolizine (73.4) with methyl propynoate in boiling tenzene or toluene containing palladium-charcoal failed, but when nitrobenzene was used, moderate-to-good yields of the pyridoquinolizine were obtained. Formation of a 4 oxo- or 4-chloro-pyridine ring from a carboxylic acid (or ester) or an acyl chloride respectively Is well documented (see pp. 378-381, and Section II.3 of this chapter) in this particular example, a fused... 

When the structure is favorable, intramolecular acylation becomes possible, as in the synthesis in 82% yield of 4-cyano-4,4a,5,6-tetrahydro-lf/-benzo[c]-quinolizin-3(2//)-one from ethyl 2-(cyanomethyl)-1,2,3,4-tetrahydro-1-quino-linepropionate 741... 

Fowler and co-workers have studied the participation of 1-acyl-l-azadienes in hetero Diels-Alder reactions, finding that vacuum pyrolysis of the O-acylhydroxamic acid (298) leads to a quinolizine system (300) through an intermediate A-acyl-l-azadiene (299) (Scheme 64), a method that was later applied to the synthesis of several quinolizine alkaloids <83JA7696, 85JOC27i9>. A similar result can be achieved by flash-vacuum pyrolysis of l-acyl-2-azetines <9UOC6729>. 

Replacement of G-acyl by nitro groups 4H-Quinolizin-4-one derivatives... 

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