Synthesis of Substituted Pyridines from Cascade [1 + 5] Cycloaddition of Isonitriles to N-Formylmethyl-Substituted Enamides, Aerobic Oxidative Aromatization, and Acyl Transfer Reaction

Abstract

A novel strategy for de novo synthesis of pyridines featuring an unprecedented α-addition of aldehyde and enamide to isonitrile as a key step is described. Under mild conditions, a cascade reaction involving Zn(OTf)2-promoted [1 + 5] cycloaddition of isonitrile with N-formylmethyl-substituted enamide, facile aerobic oxidative aromatization and intermolecular acyl transfer from the pyridinium nitrogen to the 5-hydroxy oxygen, and finally acylation of the 4-amino group by an external acyl chloride efficiently afforded 2-substituted 4-acylamino-5-acyloxypyridines in good to excellent yields.

Phosphine Ligand‐Free Ruthenium Complexes as Efficient Catalysts for the Synthesis of Quinolines and Pyridines by Acceptorless Dehydrogenative Coupling Reactions

“…Numerous synthetic protocols for the quinoline nucleus have been reported, including the Skraup, Comps, Conrad‐Limpach, Gould‐Jacobs, Doebner‐von Miller and Povarov reactions . Pyridine derivatives can be synthesized by transition metal catalyzed cycloaddition reactions . However, harsh reaction conditions, low stereoselectivity, multiple steps and low yields limit the general applicability of these methods.…”

“…[6][7][8][9][10][11][12] Pyridine derivatives can be synthesized by transition metal catalyzed cycloaddition reactions. [13][14][15][16][17][18][19][20][21][22] However, harsh reaction conditions, low stereoselectivity, multiple steps and low yields limit the general applicability of these methods. Green and atom-economic acceptorless dehydrogenative coupling (ADC) reactions are a competitive methodology for the synthesis of quinolines (a variation on the Friedländer protocol) and pyridines from 2-aminobenzyl or γ-amino alcohols with secondary alcohols or ketones.…”

Atom‐Economic Silver‐Catalyzed Difunctionalization of the Isocyano Group with Cyclic Oximes: Towards Pyrimidinediones

“…[1] Such substrates can participate in arange of reactions,such as multicomponent reactions [2] (e.g.U gi and Passerini reactions), insertion reactions, [3] and cycloaddition reactions. Considering the potential reactivity of nitrogen and carbon functionalities toward new chemical-bond formation, we can envision that exploration of both the nitrogen and carbon atoms of the isocyano group as reactive sites,t os imultaneously construct new chemical bonds in one step (difunctionalization of isocyano group), would provide opportunities for the creation of structurally new and important molecules.I nt his context, af ew groups have recently reported their pioneering work toward cycloaddition reactions between isocyanides and propargylamines, [6] between isocyanides and enamides, [7] and between two isocyanides (Scheme 1b). Considering the potential reactivity of nitrogen and carbon functionalities toward new chemical-bond formation, we can envision that exploration of both the nitrogen and carbon atoms of the isocyano group as reactive sites,t os imultaneously construct new chemical bonds in one step (difunctionalization of isocyano group), would provide opportunities for the creation of structurally new and important molecules.I nt his context, af ew groups have recently reported their pioneering work toward cycloaddition reactions between isocyanides and propargylamines, [6] between isocyanides and enamides, [7] and between two isocyanides (Scheme 1b).…”

Silver‐Catalyzed Chemoselective [4+2] Annulation of Two Isocyanides: A General Route to Pyridone‐Fused Carbo‐ and Heterocycles

“…[1][2][3][4][5][6][7][8] These reactions mainly involve the participation of activated methylene isocyanides (as at hree-atom component) in [3+ +2], [3] [3+ +3], [4] and [3+ +6] annulations [5] and of isocyanides (as ao ne-atom component) in [1+ +4], [2,6] [1+ +5], [7] and [1+ +2+ +2] annulations. [1][2][3][4][5][6][7][8] These reactions mainly involve the participation of activated methylene isocyanides (as at hree-atom component) in [3+ +2], [3] [3+ +3], [4] and [3+ +6] annulations [5] and of isocyanides (as ao ne-atom component) in [1+ +4], [2,6] [1+ +5], [7] and [1+ +2+ +2] annulations.…”