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This article discusses a Pd-catalyzed cyanation protocol for iodo nucleosides, specifically focusing on the synthesis of three bioactive nucleosides: toyocamycin, sangivamycin, and a mycalisine A precursor. The authors highlight the importance of nucleosides as potential antiviral drugs and the challenges in installing a cyano group in nucleosides. They present a method using inexpensive zinc cyanide as the cyanating source and provide detailed screening studies and experimental results. The study found that Pd2(dba)3 and N,N-dimethylacetamide (DMA) were the most effective catalyst and solvent, respectively, and other cyanating agents did not produce the desired product. The protocol was successfully applied to the synthesis of the desired bioactive nucleosides and has potential applications beyond nucleosides. [Extracted from the article]

The dimethylamino functionality has significant importance in industrially relevant molecules and methodologies to install these efficiently are highly desirable. We report herein a highly efficient, room‐temperature dimethylamination of chloroheteroarenes performed via the in‐situ generation of dimethylamine using N,N‐dimethylformamide (DMF) as precursor wiith a large substrate scope that includes various heteroarenes, purines as well as commercially relevant drugs such as altretamine, ampyzine and puromycin precursor. [ABSTRACT FROM AUTHOR]

Ruth linker is a C5 pyrimidine modified nucleoside analogue widely utilized for the incorporation of a primary amine in a synthetic oligonucleotide. The increasing demand for non-radioactive labeling, detection of biomolecules, and assembly of COVID-19 test kits has triggered a need for scale-up of Ruth linker. Herein, an efficient protocol involving a palladium-catalyzed Heck alkenylation is described. The synthesis has been optimized with a goal of low catalyst concentration, column-free isolation, high product purity, reproducibility, and shorter reaction time. The scalability and utility of the process have been demonstrated successfully on a 100 g scale (starting material). Additionally, for scale-up of the Heck alkenylation protocol, 7-phospha-1,3,5-triaza-adamantanebutane sulfonate (PTABS) as the coordinating caged phosphine ligand was also synthesized on a multigram scale after careful optimization of the conditions. [ABSTRACT FROM AUTHOR]

Regioselective amination of polyhalogenated heteroarenes (especially pyrimidines) has extensive synthetic and commercial relevance for drug synthesis applications but is plagued by the lack of effective synthetic strategies. Herein, we report the Cu(II)/PTABS-promoted highly regioselective nucleophilic aromatic substitution (S N Ar) of polychlorinated pyrimidines assisted by DFT predictions of the bond dissociation energies of different C-Cl bonds. The unique reactivity of Cu(II)-PTABS has been attributed to the coordination/activation mechanism that has been known to operate in these reactions, but further insights into the catalytic species have also been provided.