Advances in Base‐Mediated Post‐Ugi Transformations via Peptidyl Anion Trapping

Abstract

Advances in base‐mediated post‐Ugi transformations are reported and discussed. The minireview encompasses reports showing the abstraction of an alpha proton adjacent to amide carbonyl in aldehyde‐derived Ugi adducts under basic conditions to perform intramolecular and intermolecular cyclizations. The methodologies have been broadly classified depending on the peptidyl anion trapping under metal‐free, metal‐catalyzed, microwave‐assisted, and external electrophile‐aided reaction conditions. A comprehensive analysis of the methods has been presented, highlighting the importance in synthetic and medicinal chemistry.

Synthesis of Indoline‐Fused 2,5‐Diketopiperazine Scaffolds via Ugi‐4CR in the Basic Mediated Tandem Consecutive Cyclization

“…Using an excessive amount of base at 50 °C with extended reaction time resulted in the formation of multiple by‐products. The pyridine‐2‐carboxaldehyde gave pyrrolidine‐2,5‐dione derivative 7 va (20%) via the formation of a β ‐lactam intermediate, followed by ring expansion [25a,28] . The molecular structures of 7 ta , 7 ua , and 7 va were further confirmed by single‐crystal X‐ray diffraction analysis.…”

“…[24] Among the IMCRs, Ugi fourcomponent reactions (U-4CRs) and the sequenced post-transformation strategy is the most powerful tool to synthesize a large number of heterocyles. [25] Recently, the indoline-fused "2,4-DKP" and "2,5-DKP" scaffolds were synthesized through post-Ugi multicomponent reactions. [26] Our research team has also used Ugi-4CR to prepare highly functionalized hybrid heterocyclic structures as part of our research for the development of new one-pot tandem consecutive reactions based on multicomponent reaction chemistry.…”

Synthesis of Azaspiro Tricyclic Scaffolds through Post‐Ugi Modifications: Scope and Limitation of Aza‐Michael Cyclization

“…The formation of α‐ketoamide might be due to acidic proton abstraction by base‐forming peptidyl anion, which was trapped by oxygen to give α‐ketoamide (Scheme 4). [2e,15,16] However, with the azaspiro[4.5]trienones 8 ad and 8 ae , the corresponding products 9 ad and 9 ae were isolated in 62 % and 50 % yields, respectively, without any formation of α‐ketoamide (Scheme 4). In the case of p ‐CN and p ‐NO 2 phenyl containing azaspiro[4.5]trienones ( 8 af and 8 ag ), the reaction was sluggish and gave a complex mixture of uncharacterizable products (Scheme 4).…”

Rapid access to C2-quaternary 3-methyleneindolinesviabase-mediated post-Ugi Conia-ene cyclization

“…Recently, inter- or intra-molecular cyclization between acidic protons at tertiary carbons of Ugi adducts and alkyne motifs has provided a straightforward way to access diverse bioactive heterocyclic architectures. 9 Notably, the activation of the alkyne moiety of this strategy is usually either by metal catalysts such as gold and sliver 10 or tethered with carbonyl groups. For example, Frank and co-workers reported a sequential indium-catalysed intramolecular post-Ugi 5- exo -dig Conia-ene cyclization approach, leading to the formation of diketopiperazinoindolines in three operational steps (Fig.…”