C2-Selective Palladium-Catalyzed C–S Cross-Coupling of 2,4-Dihalopyrimidines

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

Under most conditions, 2,4-dihalopyrimidines undergo substitution reactions at C4. Here we report that Pd(II) precatalysts supported by bulky N-heterocyclic carbene ligands uniquely effect C2-selective cross-coupling of 2,4-dichloropyrimidine with thiols. The regioselectivity this reaction stands in stark contrast to ∼1500 previously reported Pd-catalyzed cross-couplings favor C4 the absence other substituents on pyrimidine ring. Selectivity catalytic system herein is extremely sensitive structure precatalyst, largely due competing C4-selective nucleophilic aromatic substitution. C2-selectivity high 1° thiols and thiophenols, a range substituted dichloropyrimidines can be used. atypical selectivity transformation may facilitate diversity-oriented synthesis, as demonstrated for derivatives an antiviral agent. these C2─Cl cleavage not take place through typical oxidative addition pathway.

Language: Английский

Regioselective Suzuki–Miyarua Cross-Coupling for Substituted 2,4-Dibromopyridines Catalyzed by C₃-Symmetric Tripalladium Clusters

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 90(5), P. 1895 - 1904

Published: Jan. 24, 2025

Multipalladium clusters possess peculiar structures and synergistic effects for reactivity selectivity. Herein, C3-symmetric tripalladium (1, 0.5 mol %) afford C2-regioselective SMCC of 2,4-dibromopyridine with phenylboronic acids or pinacol esters (C2:C4 up to 98:1), in contrast Pd(OAc)2 ligand-free conditions. In addition, similar C2-selectivity was achieved Sonogashira, Negishi, Kumada coupling reactions. This method highlights their powerful catalytic ability, exclusive C2-selectivity, broad substrate scope, efficient amplification, multiple ligand-exchange feasibility demonstrates that the conventional sites could be successfully regulated even reversed by catalysts.

Language: Английский

“Large-but-flexible” palladium-NHCs complexes catalyzed site-selective Suzuki coupling of 2,5-dichloropyridine

Molecular Catalysis, Journal Year: 2024, Volume and Issue: 572, P. 114758 - 114758

Published: Dec. 9, 2024

Language: Английский