Alkyl quinolizines, synthesis

A recent quinolizine synthesis used the reactivity of both C- and N-alkyl groups in picolinium quaternary salts isa ... 

A recent formal synthesis of the alkaloid (—)-mitralactonine relied on a reaction that allowed the simultaneous creation of three new bonds, two of them a and one ft with respect to the quinolizine nitrogen. As shown in Scheme 112, treatment of triptamine with chiral aldehyde 480 in the presence of acid directly gave a mixture of diastereo-meric indoloquinolizidines 481 and 482 through a mechanism involving a Pictet-Spengler cyclization and a N-alkylation reaction <2007SL79>. 

Another related photocyclodehydrogenation synthesis uses an N- styrylpyridinone (164 Scheme 92), which is generated by N- alkylation of pyridinone with a styryl bromide. Irradiation in acid solution in the presence of oxygen causes isomerization and cyclodehydrogenation to afford 4//-benzo[a]quinolizin-4-one (165) and its 7-phenyl derivative (166) in yields of 37% and 60% respectively (77JOC1122). 

The scope of this process has been extended in a more detailed investigation to the synthesis of quinolizines [175] and the influence of alkyl substituents in various positions of the aminodialkene substrate on product diastereoselectivity was probed. Neodymium-based catalysts are particularly efficient for six-membered ring formation (40). The methodology has found further application in the synthesis of tri- and tetracyclic alkaloidal skeletons (41) [176]. 

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