Westphal condensations synthesis

The Westphal condensation was applied to the synthesis of sempervirine (289) (68JOC3985). Quaternary salt 287 reacted with 1,2-cyclohexanedione in the presence of dibutylamine to give quinolizinium salt 288 (48%), which was hydrolyzed (93%) and decarboxylated (85%) to afford 289. 

Two additional examples of the Westphal synthesis which do not lend themselves to tabular treatment are the condensation of l-ethoxycarbonylmethyl-5,6,7,8-tetrahy-droquinolinium bromide (201 Scheme 107) with diacetyl to yield a quinolizinium ion (202) having a 1,9-trimethylene bridge, and the condensation of l-ethoxycarbonylmethyl-2-methylpyridinium bromide with phenanthroquinone (Scheme 108) to yield phenanthro[9,10-6]quinolizinium bromide. 

Some general reactions of the azinium salts (198) produced by reacting a-halogenocarbonyl compounds (197) with a-methylazines (196) are shown in Scheme 46. They cyclize in the presence of base to give pyrroloazines (199) or alternatively condense with a-diketones to give pyridoazinium salts (200) (the Westphal synthesis). 

A modification of the Westphal synthesis is based on fS-(2-pyridyl)substituted fS-hydroxyketones 18, which are available from aldol addition of pyridine-2-aldehyde to methylene ketones R -CH2-CO-R. O-Acylation and subsequent N-quaternization with bromoacetate or bromoacetonitrile transform 18 into pyridinium salts 19, which on treatment with BU2NH are cyclized to quinoHzinium salts 20 by intramolecular aldol condensation and HOAc ehmination ... 

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