One-Pot Synthesis of 1,2-Dihydropyridines: Expanding the Diverse Reactivity of Propargyl Vinyl Ethers

Abstract

The catalyzed synthesis of 1,2-dihydropyridines starting from easily accessible propargyl vinyl ethers was realized. The reaction sequence involving a transition metal-catalyzed propargyl-Claisen rearrangement, a condensation step, and a Brønsted acid-catalyzed heterocyclization furnishes the highly substituted heterocycles in moderate to excellent yields. Additionally, a practical one-pot protocol toward 1,2-dihydropyridines and 2H-pyrans starting from propargylic alcohols was developed.

Metal-Catalyzed Cascade Rearrangements of 3-Alkynyl Flavone Ethers

“…Use of transition metal catalysts such as Au(I), 2 Ag(I), 3 Pd(II), 4 Rh(I), 5 Cu(I) 6 and Fe(III) 7 for alkynyl-Claisen rearrangements has been reported. Subsequent one-pot cascade reactions to access heterocycles including furans, pyrroles, 2H- pyrans, and dihydropyridines have also been reported by the Kirsch 2b,3b-d and Jiang laboratories. 4b,6,7 Moreover, Kozlowski and coworkers have reported the first asymmetric Saucy-Marbet rearrangement of propargyl-substituted indoles to afford allenyl oxindoles or spirolactones catalyzed by Pd(II)/BINAP.…”

Au-Catalyzed Synthesis and Functionalization of Heterocycles

“…Kirsch and coworkers reported a gold-catalyzed tandem cyclization/1,2migration of 2-alkynyl-2-hydroxy carbonyl compounds (197) to yield fully substituted 3(2H)-furanones 198. On the other hand, when the tandem process is performed with their 2-silyloxy analogs, in the presence of N-iodosuccinimide, fully substituted 3(2H)iodofuranones (199), resulting from an iododemetalation, are obtained (Scheme 66) [176]. On the other hand, when the tandem process is performed with their 2-silyloxy analogs, in the presence of N-iodosuccinimide, fully substituted 3(2H)iodofuranones (199), resulting from an iododemetalation, are obtained (Scheme 66) [176].…”

“…These reactions proceed via intramolecular attack of the carbonyl to the initially generated cyclopropyl gold-carbenes (228) to form oxonium cations of type 229, which undergo a Prins-type cyclization with concomitant catalyst regeneration [164]. The process is initiated by a endo cycloisomerization to afford the gold-carbene intermediate 240, which subsequently undergoes a stepwise [3 + 2] cycloaddition with an electron-rich alkene (i.e., styrene or enol ether) to afford the final dihydrofuran core (Scheme 76) [198,199]. 1) [166] or englerins A and B [165,194].…”

“…The Claisen rearrangement of 1,5-enynes to allenes has also been employed in the synthesis of dihydropyridines [199]. An example of this was reported by Xu et al, who prepared pyridines 238 via a gold-catalysed reaction of 1,5-enynes 237 in the presence of tosylamine (Scheme 60) [200].…”

Synthesis, utility and medicinal importance of 1,2- & 1,4-dihydropyridines

“…et al 21 with internal alkynes 74a-o and used a sequential addition of reagents and catalysts to obtain reproducibly high yields [(i) AuCl (5 mol%), 23 C; (ii) R 3 NH 2 (57d, 62a, 62c, 62h…”