Title : Facile and effective amide bond formation through direct acylation of inactivated esters
Abstract:
Amide bond is arguably the most fundamental functionality in organic chemistry. Yet, new strategies are always needed to meet the contemporary synthetic challenges. Classical methods, using coupling agents, metal catalysts or harsh reaction conditions become less and less favored due to reasons, such as atom economy, energy efficiency and the implementation of green synthetic processes. A very promising approach is the direct coupling of inactivated esters and amines in mild conditions, in the presence of a strong base. The method is inexpensive, due to the affordability of the inactivated esters; it does not require toxic metal catalysts or auxiliary reagents; it often works at room temperature; the reactions are generally fast and with good yields.
Our interest in the exploration of the direct acylation of amines with inactivated esters is based on some weaknesses in the current state of this research. The existing literature suffers from non-systematic approach; fractionalized data, lack of diversity in the used substrates without a complete overview of the reaction’s scope and limitations. Virtually there are no reports of unsuccessful experiments, which can create a misconception that the reaction is universal towards all esters and amines. There are no attempts to find a practical application i.e., the implementation of the new reaction setting for the synthesis of a valuable commercial or scientific products.
We therefore report a comprehensive study of over 85 reactions, covering a wide range of substrates, with thorough examination of the scope and the limitations of the reactions settings and with practical applications of each reaction system.
