Studies on β-Enaminonitriles: A one-pot Regiospecific Synthesis of Polysubstituted 3,4-Dihydro-2(1H)-Pyridones

Enantioselective Synthesis of Dihydropyridinones via NHC-Catalyzed Aza-Claisen Reaction

“…Hickmott has demonstrated that the reaction of enamines such as 34 with α,β-unsaturated acid chlorides 35 proceeded first via N-acylation over C-alkylation, which gave an intermediate that underwent a sigmatropic rearrangement, possibly via the intermediacy of a ketene (Scheme ). Building on these results and those of Stork and Stille, Mahalanabis has invoked this mechanistic rationale in the synthesis of 33 from acyl chloride 38 and enamine 39 (Scheme ). In a slight departure from these precedents, we favor a reversible 1,2 addition of the enamine to II to form hemiaminal III , an argument that parallels our previous studies , and the well-documented properties of acyl azoliums. − …”

KOtBu-mediated annulation of acetonitrile with aldehyde: synthesis of substituted dihydropyridin-2(1H)-ones, pyridin-2(1H)-ones, and thiopyridin-2(1H)-ones

“…[5][6][7][8][9][10][11][12][13] The coupling of a,b-unsaturated acid chloride and ester with enaminonitrile and sodium cyanomethanide, respectively, have been studied for the synthesis of dihydropyridinones. [5][6][7][8]11,12 Bode et al and Biju et al synthesized dihydropyridinones enantioselectively by the coupling of a,b-unsaturated aldehydes with various imine derivatives catalysed by N-heterocyclic carbene. 10 Nonetheless, these methods required prefunctionalized substrates to obtain dihydropyridin-2(1H)-ones and pyridin-2(1H)-ones.…”

“…4 In view of their biological importance, several synthetic methods have been presented in the literature (eqn (1), Scheme 1). [5][6][7][8][9][10][11][12][13] The coupling of a,b-unsaturated acid chloride and ester with enaminonitrile and sodium cyanomethanide, respectively, have been studied for the synthesis of dihydropyridinones. [5][6][7][8]11,12 Nonetheless, these methods required prefunctionalized substrates to obtain dihydropyridin-2(1H)-ones and pyridin-2(1H)-ones.…”

“…[5][6][7][8][9][10][11][12][13] The coupling of a,b-unsaturated acid chloride and ester with enaminonitrile and sodium cyanomethanide, respectively, have been studied for the synthesis of dihydropyridinones. [5][6][7][8]11,12 Nonetheless, these methods required prefunctionalized substrates to obtain dihydropyridin-2(1H)-ones and pyridin-2(1H)-ones. Prefunctionalized substrates, such as a,b-unsaturated acyl chloride, esters, sodium cyanomethanide, and b-aminonitrile, are either expensive or difficult to handle.…”

Unexpected formation of 4,4,6-trimethyl-2-oxo-1-phenyl-1,2,3,4-tetrahydropyridine-3-carbonitrile via Tandem Knoevenagel condensation-Michael addition-intramolecular cyclization

“…Such structures are generally obtained by condensation of aliphatic ketones with cyanoacetamides [2] or of cinnamic acid chloride with substituted 3-aminoacrylonitriles [3]. We previously proposed a new synthesis of 4,4-disubstituted tetrahydropyridines by reaction of substituted ethyl crotonoates with cyanothioacetamide and N-methylmorpholine [4].…”