Direct Construction of 2-Aryliminochromenes from Arynes, N,S-Keteneacetals, and DMF

Abstract

A concise and direct synthetic strategy for the construction of 2-aryliminochromene skeleton by cascade three-component coupling reaction of arynes, N,S-keteneacetals, and DMF in good yields has been disclosed. The process demonstrates the first example of aryne chemistry combined with N,S-keteneacetals. Using this strategy, an expeditious synthesis of biologically important arylimino-2H-chromene-3- carboxamides was achieved.

Beyond a solvent: triple roles of dimethylformamide in organic chemistry

“…Aer a couple of years, Li and co-workers synthesized 2-aryliminochromenes 83 by a transition-metal-free reaction between arynes, N,S-keteneacetals 82 and dimethylformamide, where dimethylformamide acts as a source of oxygen to form chromeneskeleton 83 (Scheme 38). 125 Ortho-Quinone methide 84 produced by [2 + 2] cycloaddition of aryne with DMF was efficaciously coupled with ester enolates or ketenimine anions under a [4 + 2] cycloaddition to provide direct access to various coumarins 87, which included integral and key parts of active biological compounds and pharmaceuticals (Scheme 39). 126 The mechanism of this reaction is depicted in Scheme 40 and begins with a nucleophilic attack of oxygen of DMF to benzyne to afford the resulting zwitterion (88) 127 which is subjected to intramolecular cyclization to furnish benzoxete 89.…”

“…After a couple of years, Li and co-workers synthesized 2-aryliminochromenes 83 by a transition-metal-free reaction between arynes, N , S -keteneacetals 82 and dimethylformamide, where dimethylformamide acts as a source of oxygen to form chromeneskeleton 83 ( Scheme 38 ). 125 …”

Aryne-Based Multicomponent Coupling Reactions

“…Miyabe, 58 Yoshida, 59 Li, 60 and Gogoi 61 independently explored this transformation by using different active methylene species including acetyl acetones, -keto esters, ester enolates, ketenimine anions, N,S-ketene acetals, and methyl-2-(bromomethyl)acrylates.…”

Transition-Metal-Free Activation of Amide Bond by Arynes

“…The trapping reactions of transient intermediates generated from arynes precursors and DMF with a variety of reactants have been widely studied as being synthetic approaches to oxygen atom-containing heterocycles [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. The synthesis of 2 H -coumarin derivatives was also studied [ 34 , 35 , 36 ]. Three-component coupling reactions leading to chromene 48 was achieved by the use of acetate 47, having an aryl group as a nucleophile for trapping the unstable intermediate ( Scheme 18 ).…”

“…In the presence of KF, the reaction of triflate 23 and acetate 47 was carried out in DMF at 80 °C to give the coumarin 48 in 95% yield [ 35 ]. The synthesis of 2-aryliminochromene skeleton of biologically active compounds was studied by using a three-component coupling reaction [ 36 ]. A transient intermediate, generated from triflate 23 and DMF, could be trapped by N , S -keteneacetal 49 to give the biologically important arylimino-2 H -chromene-3-carboxamide 50 in 81% yield.…”