Reaction of β‐(2‐aminophenyl)‐α,β‐Ynones with Tosyl Isocyanate: Experimental and Computational Investigations

Abstract

A practical metal-free approach to the synthesis of 2-aroyl-N-tosyl-1H-indole-3 carboxamides through an unprecedented sequential 5endo-dig cycloamination /carboxamidation reaction of b-(2-aminophenyl)-a,b-ynones with the tosyl isocyanate is described. A computational model gives a plausible rationale for the unexpected results.

2‐(Alkynyl)anilines and Derivatives — Versatile Reagents for Heterocyclic Synthesis

“…Interestingly, when amino‐substituted ynones reacted with N ‐tosylisothiocyanates, indoles instead of quinolines were produced [129] …”

Divergent Sequential Reactions of β‐(2‐Aminophenyl)‐α,β‐ynones with Malonyl Chloride

“…DMF acted as a dual synthon to afford methine and N , N ‐dimethyl functionality [8] . The reaction of compounds 1 with tosyl isocyanate allowed an efficient approach to 2‐aroyl‐ N ‐tosyl‐1 H ‐indole‐3‐carboxyamides through unprecedented 5‐endo‐dig cycloamination/carboxamidation reactions [9] …”

“…[8] The reaction of compounds 1 with tosyl isocyanate allowed an efficient approach to 2-aroyl-N-tosyl-1Hindole-3-carboxyamides through unprecedented 5-endo-dig cycloamination/carboxamidation reactions. [9] N-addition reaction of isocyanates followed by regioselective 6-exo-dig cyclization to the corresponding quinazoline scaffolds was observed when the phenyl isocyanate was used instead of the tosyl isocyanate. Moreover, the key factors directing the reaction of β-(2-aminophenyl) α,β-ynones 1 with a variety of aryl isocyanates/isothiocyanate towards the formation of the product of N-cyclization vs. the formation of O-/S-cyclization were addressed.…”