Toward Pyrrolo[2,3-d]pyrimidine Scaffolds

Abstract

Herein, we present a new route to highly substituted pyrrolo[2,3-d]pyrimidines featuring a Ugi-Smiles/Sonogashira cascade followed by an efficient base-catalyzed intramolecular cyclization. When formaldehyde is chosen as input in the Ugi-Smiles step, aromatic fused systems are eventually obtained through the isomerization of an exo-alkylidene intermediate.

The Ugi–Smiles and Passerini–Smiles Couplings: A Story About Phenols in Isocyanide‐Based Multicomponent Reactions

“…As well as in the Heck‐type reaction, the Ugi–Smiles adducts of o ‐iodo‐hydroxyaromatics could also be used as partners in Sonogashira couplings, leading to final formation of indoline derivatives. Cyclization on the alkyne moiety was easily achieved under slightly basic conditions when an aromatic aldehyde was used in the Ugi step (Scheme ) 39. The choice of an aliphatic aldehyde in the same sequence required stronger conditions for cyclization and led to a surprising activation of a tethered N ‐benzyl residue (Scheme ) 40…”

Synthesis of Structurally Diverse Emissive Molecular Rotors with Four-Component Ugi Stators

“…Next, we turned our attention to explore the alternative pathways B or C, which employ the Sonogashira coupling after synthesizing the Ugi adduct and differ only in the precursors (Scheme ). It is important to mention that examples of these coupling reactions starting from Ugi adducts are relatively scarce, and they are limited to postcondensations, usually cyclizations . It was immediately noticed that one of the requirements for these routes to work was the inclusion of a halogen atom in Ugi structure, which could later be cross-coupled with an ethynyl moiety.…”

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

“…El Kaïm et al in 2010 reported an Ugi-Smiles/Sonogashira cascade reaction, followed by base-mediated intramolecular cyclization to access biologically relevant pyrrolopyrimidines 9(E) and 9(Z) respectively (Scheme 3). [38] When formaldehyde was in the Ugi-Smiles reaction, completely saturated pyrrolopyrimidines 10 and 11 were afforded through isomerization of an exo-alkylidene intermediate. Putative reaction mechanism involved deprotonation of the amide, leading to enolate formation for a 7-exo-dig cyclization.…”