Post‐Ugi Cyclizations Towards Polycyclic N‐Heterocycles

Abstract

The Ugi reaction has become one of the highly explored reactions for the formation of multifunctional adducts, due to the mild reaction conditions, wide scope and high variability. By carefully selecting the starting four components, Ugi‐adducts could undergo different kinds of post‐transformations for the synthesis of bioactive heterocycles, natural products and macrocycles. Considering the significance of polycycles, diverse post‐Ugi transformations have been developed over the years for constructing structurally novel polycycles. In this account, we summarize important efforts for the synthesis of polycyclic N‐heterocycles via post‐Ugi cyclizations from the Van der Eycken laboratory onwards 2016. With the aid of transition metal catalysis from gold, rhodium, silver and palladium, as well as metal‐free strategies, versatile polyheterocycles are prepared with high efficiency and step‐economy.

A Facile Ugi/Ullmann Cascade Reaction to Access Fused Indazolo-Quinoxaline Derivatives with Potent Anticancer Activity

“…As an evergreen in organic chemistry, multicomponent reactions (MCRs) never became old-fashioned or tedious [ 29 , 30 , 31 , 32 , 33 ], because they always inspire creative spirits by following the fundamental quest: more than two compounds are reacted in a one-pot fashion to form two or more bonds. The post-Ugi reactions [ 34 , 35 , 36 , 37 ], as typical MCRs, are well suited for the construction of important heterocycles, macrocycles, polymers, and other compounds in drug discovery and natural product synthesis [ 38 , 39 , 40 , 41 , 42 , 43 ]. In the course of our continued study on the construction of novel N -fused heterocyclic chemical spaces and activity evaluation from Ugi adductive [ 28 , 36 , 44 , 45 , 46 ], we hoped to establish a highly efficient diversity-oriented synthetic route to indazole-fused polycyclics utilizing a sequential one-pot Ugi/Ullmann reaction, as shown in Scheme 1 d. We reasoned that the Ugi product involving 3-carboxyindazole and 2-bromoaniline would undergo an intramolecular Ullmann cyclization cascade process to yield the indazolo-quinoxaline derivatives.…”

Recent Advances in the Synthesis of Rosettacin

“…Compared with all-carbon cycles, heterocycles often own different physical and chemical properties due to the presence of heteroatoms [1][2][3][4][5][6][7]. Thus far, heterocycles are the largest branch of organic compounds.…”

Chemical insights into the synthetic chemistry of five-membered saturated heterocycles—a transition metal–catalyzed approach

“…On the other hand, heterocycles are of immense importance, and therefore, scientists are making exhaustive efforts to synthesize these heterocyclic compounds through novel, cost-effective, and green synthetic transformations ( Ibad et al, 2010 ). Among all the available synthetic techniques, transition metal–catalyzed reactions are the most popular for the synthesis of heterocyclic compounds due to the fact that complicated molecules can be easily synthesized from readily available starting materials under mild reaction conditions ( Ullah et al, 2010a ; Khera et al, 2010 ; Tang et al, 2023b ).…”