Novel 2,2-Bipyridine Ligand for Palladium-Catalyzed Regioselective Carbonylation

Abstract

[reaction: see text] A palladium-catalyzed highly regioselective one-step carbonylation of 2,5-dibromo-3-methylpyridine is reported. A range of alkyl esters and amides can be prepared in good yield with better than 95:5 regioselectivity via this method. Key to the high regioselectivity for the formation aromatic amides is the introduction of a novel nonphosphine-based 2,2-bipyridine ligand. This novel reaction was scaled up smoothly in the plant to a 130-kg batch size and facilitated the delivery of bulk material for the clinical trials of Sch 66336, a candidate for oncologic treatments.

Alkoxy- and amidocarbonylation of functionalised aryl and heteroaryl halides catalysed by a Bedford palladacycle and dppf: a comparison with the primary Pd(ii) precursors (PhCN)2PdCl2 and Pd(OAc)2

“…Having established an improved protocol for amidocarbonylation of 9, regioselective amidocarbonylation of 2,5dibromopyridines 11 and 13 with piperidine was tested (Scheme 5, Table 5). 31 In general, carbonylation/coupling is expected at the 2-position (the more electron-deficient carbon centre). Several products are possible in this reaction, e.g.…”

Palladium‐Catalyzed Carbonylation Reactions of Aryl Halides and Related Compounds

“…Until recently (hetero)aromatic bromides and iodides were most widely employed as starting materials in intermolecular alkoxycarbonylation, [10,11] aminocarbonylation, [11,12] and hydroxycarbonylation reactions. [13] The first palladiumcatalyzed alkoxycarbonylation was described by Heck and coworkers in 1974.…”

Programmed Molecular Construction: Driving the Self-Assembly by Coordination and Hydrogen Bonds Using 6-(Pyridin-2-yl)-1,3,5-triazine-2,4-diamine with M(NO3)2 Salts

“…11−17 Many functional materials with 2,2′-bipy and related ligands have been developed and applied to material separation/purification, catalysis, and ions exchange. 18−23 However, these materials are comparatively difficult to prepare because their syntheses are laborious. In addition, crystal structures with 2,2′-bipy complexes are not predictable due to lack of functional groups to direct the self-assembly.…”

“…In coordination chemistry, ligand like 2,2′-bipyridine ( 1 = 2,2′-bipy) has been widely used due to its chelating ability (in self-assembly with metal ions) to form predictable coordination complexes. − Many functional materials with 2,2′-bipy and related ligands have been developed and applied to material separation/purification, catalysis, and ions exchange. − However, these materials are comparatively difficult to prepare because their syntheses are laborious. In addition, crystal structures with 2,2′-bipy complexes are not predictable due to lack of functional groups to direct the self-assembly.…”