Unequivocal synthesis of N-substituted 1,4-dihydropyridines

Abstract

References and Notes(1) (a) F.

Nitropyridyl isocyanates in 1,3‐dipolar cycloaddition reactions

“…It is not known that the acyl azide precursors react with the resulting isocyanate products in the Curtius reaction [3]. Reaction with some other organic azides however, gives the 1,3-dipolar cycloadducts [3][4][5].…”

“…TMSA behaves as a 1,3-dipole in analogy to organic azides towards acetylenes [10], olefins [4][5]11] and nitriles [11,12]. The corresponding cycloadducts are formed.…”

“…Reaction of TMSA with acid chlorides [13,14], anhydrides [14][15][16][17], imides [16], esters and lactones [18] affords a variety of isocyanates. In some cases these are cyclized directly to heterocyclic compounds, like uracils [16], pyridones [14], dihydropyridines [5], triazoles [12] and aziridines [4]. The reaction of TMSA with heterocumulenes, such as isocyanates, isothiocyanates, carbodiimides and diphenylketene, has received little attention.…”

“…The 1,3-dipolar cycloaddition of aromatic isocyanates (1) to pyridine N-oxides (3) is a well known reaction (Scheme 2) [23][24][25][26][27][28][29][30][31] and has been studied since the early 1980's. The reaction has been considered to be a 1,3-dipolar cycloaddition to the nitrone function, followed by [1,5]sigmatropic rearrangement and re-aromatization by decarboxylation. The 1,2-dihydro intermediates (4) are too unstable neither to be seen during the reaction nor isolated from the reaction mixtures.…”

“…The 1,2-dihydro intermediates (4) are too unstable neither to be seen during the reaction nor isolated from the reaction mixtures. The 2,3-dihydro intermediates (5) formed from the intermediates (4) through a [1,5] sigmatropic shift, are more stable [23][24][25][26][27][28][29][30][31] and have sometimes been isolated and characterised. This is in agreement with calculations performed, which showed that the heat of formation of the rearranged compound is lower in energy than that of the adduct precursor, indicating the adduct precursor to be thermodynamically less stable [27].…”