A Very Efficient Cerium(IV) Ammonium Nitrate Catalyzed, Four‐Component Synthesis of Tetrahydropyridines and Its Application in the Concise Generation of Functionalized Homoquinolizine Frameworks

Abstract

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.

A β‐Enaminone‐Initiated Multicomponent Domino Reaction for the Synthesis of Indoloquinolizines and Benzoquinolizines from Acyclic Precursors

“…Subsequent steps include a Michael addition of I to the unsaturated aldehyde to give II , which would then undergo a 6‐ exo ‐ trig cyclization to a cyclic hemiaminal III . According to our experience,8j this intermediate is unstable and reacts with the ethanol present in the reaction medium to afford IV , which would be in equilibrium with species V , a vinylogous acyliminium cation. Finally, a Pictet–Spengler reaction would afford the observed products 2 .…”

“…Since our discovery that cerium(IV) ammonium nitrate (CAN)6 is an excellent catalyst that allows the very fast synthesis of β‐enaminones from β‐dicarbonyl compounds and primary amines,7 we have described a number of CAN‐catalyzed domino and multicomponent reactions initiated by the formation of a β‐enaminone 8. One of the methods thus discovered allowed the one‐pot, efficient preparation of 1‐alkyl‐6‐ethoxy‐1,4,5,6‐tetrahydropyridines from primary amines, β‐dicarbonyl compounds, α,β‐unsaturated aldehydes, and alcohols 8j…”

Fully Diastereoselective Synthesis of Polysubstituted, Functionalized Piperidines and Decahydroquinolines Based on Multicomponent Reactions Catalyzed by Cerium(IV) Ammonium Nitrate

“… [a] Compounds 4 r and 4 t are known 27. [b] This compound was isolated as a mixture with the corresponding 6‐ethoxy‐1,2,3,4‐tetrahydropyridine, a mixture that was reduced without separation to give 6 u . …”

Ceric Ammonium Nitrate (CAN)–Catalyzed Multicomponent Reactions: An Efficient Catalyst for Green Organic Synthesis

“…[28] Another protocol for the preparation of tetrahydropyridine derivatives have been developed by Maiti and co-authors using CAN as a catalyst in acetonitrile (CH 3 CN) (Scheme 10, Method 2). [29,30] Wang …”