Multicomponent Reactions for the Synthesis of Complex Piperidine Scaffolds

Abstract

Auf direktem Weg zur Diversität: Mehrkomponentenreaktionen führen effizient zu Piperidinen mit vielfältigen Gerüsten, Funktionalisierungsmustern und stereochemischen Eigenschaften (siehe Schema, X=OR, NR2). Eine Verknüpfung der Säurechlorid‐Komponente mit dem Dienophil ergibt über eine intramolekulare Diels‐Alder‐Reaktion der in situ erzeugten Azadiene polycyclische Piperidine.

Intermolecular [3+3] ring expansion of aziridines to dehydropiperi-dines through the intermediacy of aziridinium ylides

“…Piperidines rank as the most prominent N-heterocyclic pharmacophore in current drugs on the market, appearing in~55% of all FDA-approved drugs containing at least one N-heterocycle, as well as in numerous bioactive natural products 3 . Convergent methods that unite multiple reactive fragments, particularly hetero-[4+2] cycloadditions, deliver substituted dehydropiperidines in enantioenriched form [21][22][23][24][25][26][27][28][29][30][31] ; however, critical substrate and/or catalyst control over regio-and stereoselectivity is challenging and often results in narrow scope. Traditional preparations of stereodefined piperidines using intramolecular S N 2-type reactions require selective installation of functional groups prior to ring closure, resulting in lower efficiency, modularity, and step economy as the desired target's complexity increases 3 .…”

Schiff Bases and Their Metallic Derivatives: Highly Versatile Molecules with Biological and Abiological Perspective

“…• Reaction of aldehydes/ketones with primary amines under acidic/basic conditions [30] • Aldol-like condensation of aldehyde [31] • Oxidative synthesis of imines from alcohols and amines [32] • Addition of organometallic reagents to cyanides [33] • Reaction of phenols and phenol-ethers with nitriles [34] • Reaction of metal amides [35] • Synthesis of ketimines from ketals [ • Reaction of olefins and tertiary alcohols with hydrazoic acid [37] • Conversion of α-amino acids into imines [38] • Reduction of nitro compounds [39]…”

A Three‐Component Reaction Based on a Remote‐Group‐Directed Dynamic Kinetic Aza‐Michael Addition: Stereoselective Synthesis of Imidazolidin‐4‐ones

“…Multicomponent reactions (MCRs) have become an important synthetic strategy in organic synthesis to build up structural and functional complexity owing to their reaction efficiency, low cost, and atom economy. [24] However, due to the coexistence of multiple substrates and functional groups, the chemo-and stereoselectivity of MCRs remains a challenge. The three-component reaction was carried out by mixing 1 a, 2 a, and 5 a directly in ethanol in the presence of trifluoroacetic acid (TFA; Table 1, entry 2).…”