The Ugly Duckling Metamorphosis: The Ammonia/Formaldehyde Couple Made Possible in Ugi Reactions.

Abstract

Ugi reactions are still a challenge when the concomitant use of ammonia and formaldehyde is required. Herein, we propose a strategy to overcome this challenge using hexamethylenetetramine (HMTA) as a singular key for the employment of these two simple starting materials in the Ugi reaction. Acylaminoacetamide derivatives were prepared in good to excellent yields by this new methodology. The scope and optimization of the reaction conditions were investigated. This novel methodology was successfully applied in the synthesis of two different diketopiperazines (DKPs) using the Ugi/Deprotection + Activation/Cyclization (UDAC) method. A continuous flow approach was also used in this methodology.

Solvent Dependent Competitive Mechanisms for the Ugi Multicomponent Reaction: A Joint Theoretical and Experimental Study in the α-Acyl Aminocarboxamides vs α-Amino Amidines Formation

“…The Ugi MCR is among the most investigated MCRs, as recently reviewed . Despite its importance and the large number of available publications, several debates surrounding the Ugi MCR are noted. − One aspect still debated is the mechanism associated with this unique isocyanide MCR (Scheme ), especially considering the challenges associated with the investigation of multicomponent transformations. ,, For instance, established mechanistic views related to the Ugi four-components transformation have been challenged . Indeed, as will be discussed herein, fine details about the mechanism of this MCR have been emerging in less than one decade.…”