The Ugi Multicomponent Reaction for the One-Step Construction of Macrocycles

The exploration of macrocycles began in the 20th century, coinciding with the progressive advancement of synthetic chemistry methodologies. From numerous synthetic strategies, the Ugi reaction stands out as an efficacious four-component reaction (4-CR). The Ugi reaction is particularly distinguished by its robust functional group tolerance, enabling the creation of macrocycles that are both diverse and complex in a singular synthetic step. This review collates contemporary examples of synthetic macrocycles, all of which have been crafted using the Ugi reaction to construct these macrocyclic frameworks. The employment of various bifunctional reagents (with the same or different groups), has introduced a plethora of cyclization tactics, resulting in the synthesis of a multitude of macrocyclic or cage molecules. In order to offer invaluable insights into the construction of macrocycles, the use of distinct colors for the various reactants in the Ugi reaction has made the entire macrocyclic construction process transparently visible, thereby enhancing readers' understanding and sparking their interest.