A very efficient cerium(IV) ammonium nitrate catalyzed, four-component synthesis of tetrahydropyridines and its application in the concise generation of functionalized homoquinolizine frameworks.

Molecular diversity: A cerium(IV) ammonium nitrate (CAN) catalyzed, four-component reaction from very simple acyclic starting materials afforded densely substituted tetrahydropyridines, which were transformed into homoquinolizines by using a gamma-alkylation-ring-closing metathesis (RCM) sequence (see scheme).The cerium(IV) ammonium nitrate (CAN) catalyzed, four-component reaction between primary aliphatic amines, beta-ketoesters or beta-ketothioesters, alpha,beta-unsaturated aldehydes, and alcohols provided a very efficient and atom-economical access to substituted 6-alkoxy-2-methyl-1,4,5,6-tetrahydropyridines. These materials were then transformed into homoquinolizine derivatives in excellent yields by using a two-step sequence comprised of regioselective gamma-deprotonation-allylation and ring-closing metathesis reactions. The possibility of displacing the alkoxy group by allylsilane nucleophiles, presumably through a vinylogous acyliminium intermediate species, was also demonstrated.