Radical Bicyclization of 2‐Cyanoaryl Acrylamides with Dicumyl Peroxide

Abstract

A radical bicyclization of 2-cyanoaryl acrylamides with dicumyl peroxide has been developed for constructing a broad spectrum of benzo[h]naphtho [1,8-bc][1,6]naphthyridine. This reaction allows the formation of three new chemical bonds through addition of methyl radical across alkene double bond, intramolecular addition of carbon-centered radical to cyano group and cyclization of the iminyl radical cascade, and features simple reaction system and wide substrate scope.

Photoinduced Metal-Free Radical Addition/Cyclization of 2-Cyanoaryl Acrylamides to Prepare gem-Difluorinated Naphthyridinone Scaffolds

“…13 C { 1 H} NMR (100 MHz, CDCl 3 ): δ 196. 7, 164.7, 151.3, 149.6, 144.8, 143.7, 134.3, 131.6, 129.2, 128.5, 127.7, 126.8, 122.8, 115.8, 112.9, 112.5, 110.8, 69.3, 56.1, 44.6, 26.3, 12.9 9S,13S,8,9,11,12,13,14,15,16,phenanthren-3-yl)oxy)methyl)phenyl)-N-ethylacrylamide (1s). Yellow solid: 950 mg, 70%; mp (122.4−123.5 °C); R f = 0.5 (dichloromethane/methanol = 50:1).…”

“…14 Li's group reported a radical bicyclization of 2-cyanoaryl acrylamides with dicumyl peroxide to construct benzo[h]naphtho [1,8bc][1,6]naphthyridine. 15 Unfortunately, stoichiometric sacrificial oxidants and polysubstituted substrates are required in these reaction systems (Scheme 1d). Therefore, mild, wide functionality compatibility, and oxidant-free protocols to prepare Npolyheterocycles are still attractive.…”

“…Recently, an interesting strategy involving radical addition/1, n -hydrogen atom transfer/cyclization of 2-cyanoaryl acrylamide has been exploited for assembling fused quinolinones . Li’s group reported a radical bicyclization of 2-cyanoaryl acrylamides with dicumyl peroxide to construct benzo­[ h ]­naphtho­[1,8- bc ]­[1,6]­naphthyridine . Unfortunately, stoichiometric sacrificial oxidants and polysubstituted substrates are required in these reaction systems (Scheme d).…”

Visible-Light-Promoted Cascade Cyclization of 3-Ethynyl-[1,1′-biphenyl]-2-Carbonitriles with Unsaturated α-Bromocarbonyls

“…Compared to monocyclization and bicyclization reactions, tricyclization reactions have a higher cyclization efficiency and step economy, allowing for the construction of highly intricate polycyclic systems. As a continuation of our research interest in radical cascade cyclization, we herein report a novel visible-light-promoted cascade cyclization of 3-ethynyl-[1,1′-biphenyl]-2-carbonitriles with unsaturated α-bromocarbonyls. The reaction generated three C­(sp 3 )–C­(sp 2 ) bonds, one C­(sp 2 )–N bond, and three cycles to afford tetrahydrobenzo­[ mn ]­cyclopenta­[ b ]­acridines (Scheme ).…”