Ligand controlled orthogonal base-assisted direct C-H bond arylation in oxa(thia)zole-4-carboxylate series. New insights in nCMD mechanism

International audienceAlkyl- and arylphosphines have been screened in competitive C2–H/C5–H direct phenylation of oxa(thia)zole-4-carboxylates using Cs2CO3 and Rb2CO3 carbonate bases. nCMD-based C2–H selective direct phenylation was highly kinetically reduced (or enhanced) in favor (or to the detriment) of CMD-based direct C5–H phenylation with bromo- and chlorobenzene, respectively, using highly electron-rich ligands. These results gave novel experimental proof in favor of the electrophilic substitution-type mechanism for nCMD process based upon a prior nitrogen-arylpalladium complex interaction that preludes the deprotonation step

Synthesis and orthogonal functionalization of oxazolo[5′,4′:4,5]pyrano[2,3-b]pyridine by intra- and intermolecular Pd-catalyzed direct C–H bond heteroarylation

International audienceThe construction and subsequent orthogonal functionalization of a hitherto unknown oxazolo[5′,4′:4,5]pyrano[2,3-b]pyridine are reported. A palladium-catalyzed direct C–H bond functionalization methodology was used to build the tricyclic scaffold as well as to achieve the subsequent C–H bond functionalization at the C-2 position of the oxazole unit with various (hetero)aryl iodides. Remarkably, selective C–H construction and functionalization procedures preserve the chorine atom on the pyridine moiety offering a late-stage substitution site to progress drug design

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

Catalytic direct (hetero)arylation of (hetero)arenes is an attractive alternative to traditional Kumada, Stille, Negishi and Suzuki–Miyaura cross-coupling reactions, notably as it avoids the prior preparation and isolation of (hetero)arylmetals. Developments of this methodology in the oxazole series are reviewed in this article. Methodologies, selectivity, mechanism and future aspects are presented

Mechanism selection for regiocontrol in base-assisted, palladium-catalysed direct C-H coupling with halides: first approach for oxazole- and thiazole-4-carboxylates.

International audienceBoth base-assisted non-concerted metallation-deprotonation (nCMD) and concerted metallation-deprotonation (CMD) have been identified as two potent operating mechanisms in palladium-catalysed direct C-H coupling of oxazole and thiazole-4-carboxylate esters with halides through base- and solvent-effect experiments. Novel C2- and C5-selective CMD direct arylation procedures in oxazole- and thiazole-4-carboxylate series were then designed by controlling the balance between electronic and steric factors. Notably, charge interactions between the palladium catalyst and substrate were identified as a parameter for controlling selectivity and reducing the impact of steric factors in the CMD reaction