H-bond network facilitated, diversity-oriented green synthesis of valuable organic compounds via atom-economic, regio-and stereoselective reactions involving ynamides and anilines

Abstract

Diversity-oriented synthesis (DOS) enables synthetic organic chemists to access structurally diverse classes of molecules, which is highly desirable in the context of medicinal chemistry, leading to drug discovery. Herein, we report a Hbonding network mediated DOS of various structurally diverse five different classes or molecules, such as acetimidamides, ketene N,N-acetals, α-arylenamide, and some heterocycles, such as quinolines, and 3,4-dihydroquinolin-4-ols, starting from readily available ynamides and anilines in the presence of HFIP as the only reagent/solvent. Moreover, 2-amido indoles were also synthesized via a one-pot, two-step process starting from ynamide and primary anilines using CuCl2. The significant benefits of this protocol compared to the previously established synthetic methods include (a) a cost-effective, straightforward and unified approach for the diversity-oriented green synthesis of various classes of valuable molecules involving ynamides and all kinds of aromatic amines (1 o , 2 o , and 3 o ), (b) a metal-free, environmentally friendly, and scalable protocol, (c) mild reaction conditions, (d) transformations that are 100% atom-economic, (e) HFIP being the sole reagent necessary for the transformations, (f) the dual functionality of HFIP as both a Brønsted acid and a solvent, (g) the regeneration of HFIP post-reaction and its straightforward and effective recovery from the reaction mixture through distillation, (h) the reusability and efficient recyclability of HFIP without compromising the subsequent reaction's results, and (i) the ability to obtain pure products in many instances without the need for column chromatography (green synthesis).