Post-Ugi Cascade Transformations for Accessing Diverse Chromenopyrrole Collections

Abstract

Employing a build/couple/pair strategy, a serendipitous one-pot protocol for the diastereoselective construction of diverse collections of chromenopyrroles is described. This methodology features an unprecedented five-step cascade including azomethine ylide generation followed by in situ intramolecular [3 + 2]-cycloaddition. Furthermore, this protocol was extended to access enantiopure chromenopyrroles using amino acids as chiral auxiliary. Moreover, postpairing reactions were employed to increase the diversity and complexity of our pilot compound collections.

A Novel Benzopyrane Derivative Targeting Cancer Cell Metabolic and Survival Pathways

“…The recent decade has witnessed an upsurge in the employment of diversity-oriented synthesis strategies for the de novo construction of first-in-class small molecules needed for phenotypic screening campaigns [ 22 , 23 , 24 ]. Among the structural options, the benzopyrane scaffold is a privileged architecture representing the core structure of a wide range of biologically appealing molecules [ 25 ].…”

Multidirectional desymmetrization of pluripotent building block en route to diastereoselective synthesis of complex nature-inspired scaffolds

“…Borrowing inspiration from our previous reports directed toward privileged substructure diversity-oriented synthesis 29 , 30 , it was envisioned that subjecting the 4-oxocyclohexa-2,5-dienyloxy)acetaldehyde 2a , and variants thereof, to reactions with various tryptamine derivatives should lead to a structurally complex and skeletally diverse octahydroindolo[2,3-a]quinolizine scaffolds (Fig. 3 ).…”

Domino Transformations of Ene/Yne Tethered Salicylaldehyde Derivatives: Pluripotent Platforms for the Construction of High sp3 Content and Privileged Architectures

“…The orchestrated assembly of theses caffolds utilized ab uild/couple/pair strategy featuring an unprecedented five-step cascade reactiono ft he Ugi adducts( 115). [54] The established conditions tolerated variouss ubstrates with respect to both the amine (112)a nd the carbocyclic acid (113 ; Scheme 27). Furthermore, the authors reported the enantioselective synthesis of chromenopyrroles (116)b yu sing amino acids as the reaction partner,t herebyi ncreasing the 3D diversity of the compound collection.…”

“…Recently, our group reported an unexpected and modular one‐pot methodology for the diastereoselective construction of biologically relevant poly‐substituted tricyclic chromenopyrroles ( 116 ). The orchestrated assembly of these scaffolds utilized a build/couple/pair strategy featuring an unprecedented five‐step cascade reaction of the Ugi adducts ( 115 ) . The established conditions tolerated various substrates with respect to both the amine ( 112 ) and the carbocyclic acid ( 113 ; Scheme ).…”