Oxidative Cascade Reaction of N-Aryl-3-alkylideneazetidines and Carboxylic Acids: Access to Fused Pyridines

Abstract

A versatile silver-promoted oxidative cascade reaction of N-aryl-3-alkylideneazetidines with carboxylic acids is reported, providing a very efficient pathway to functionalized fused pyridines. This method allows introduction of fused pyridine ring systems to heterocycles, drugs, and natural products. A mechanistic study revealed that silver salt is essential for the chemo- and regioselective ring expansion, sequential oxidative nucleophilic additions, and oxidative aromatization. This approach represents the first example of the strained N-heterocycles undergoing a cascade reaction with a π bond and a nucleophile together.

Rh-Catalyzed Chemoselective [4 + 1] Cycloaddition Reaction toward Diverse 4-Methyleneprolines

“…General Methods for Preparation of Substrates 1 According to the Literature. 19 Compounds 1a, 1c, 1d, 1e, 1f, 1i, 1l, 1n, 1o, 19 1-(4-Methoxyphenyl)-3ethyleneazetidine (1a). R f = 0.3 (EA/PE = 1:10), yellow solid, yield: 0.54 g, 31%, mp: 50.3−51.8 °C.…”

“…3,152.1,145.6,142.9,140.0,128.8 (q,J = 31.8 Hz), 128.0, 125.7 (q, J = 269.5 Hz), 124.3 (q, J = 3.8 Hz), 114.8, 113.9, 105.8, 73.2, 61.1, 55.5, 54.6, 50.2, 12.9. 19 F NMR (376 MHz, CD 3 OD) δ −63.89. IR (film): 3040,2910,1670,1630,1450,1181,1040,741,686 .5, 153.7, 150.2, 148.4, 144.1, 141.3, 130.1, 123.9, 116.2, 115.4, 107.4, 74.6, 62.6, 56.9, 56.0, 51.4, 14.3.…”

2,3‐Dichloro‐5,6‐Dicyano‐1,4‐Benzoquinone (DDQ)‐Mediated Tandem Oxidative Coupling/Intramolecular Annulation/Dehydro‐Aromatization for the Synthesis of Polysubstituted and Fused Pyridines

“…[2] As a consequence, considerable efforts have been devoted to developing efficient approaches for the preparation of pyridines. [6] During the past few decades, a large number of alternative strategies for preparing pyridines have been successfully established such as metal-mediated cycloaddition, [7] metal-free multicomponent reaction, [8] transition-metal-catalyzed coupling of ketoxime acetates, [9] ring-expansion reaction, [10] and so on. [6] During the past few decades, a large number of alternative strategies for preparing pyridines have been successfully established such as metal-mediated cycloaddition, [7] metal-free multicomponent reaction, [8] transition-metal-catalyzed coupling of ketoxime acetates, [9] ring-expansion reaction, [10] and so on.…”

“…The traditional methods include the Hantzsch reaction, [3] Kröhnke pyridine synthesis, [4] Chichibabin reaction, [5] and Bohlmann-Rahtz reaction. [6] During the past few decades, a large number of alternative strategies for preparing pyridines have been successfully established such as metal-mediated cycloaddition, [7] metal-free multicomponent reaction, [8] transition-metal-catalyzed coupling of ketoxime acetates, [9] ring-expansion reaction, [10] and so on. [11] However, many of these reported methods suffer from the disadvantages such as harsh reaction conditions, functionalized starting materials, and use of transitionmetal catalysts in the synthesis of polysubstituted pyridines.…”

“…With the optimal reaction conditions in hand, various β-enaminoesters were investigated by new developed method ( Table 2). β-Enaminoesters 1 b-1 s, which contained electron-donating or electron-withdrawing group on the benzene ring, could react with 1,3-diphenylpropene 2 a smoothly (entries [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. The corresponding polysubstituted pyridines 3 b-3 s were obtained in 60-90% yields.…”