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Evidence for an interphase deprotonation of Pd(II)-amine complexes with weak carbonate base has been gained for the first time. When a rate-limiting deprotonation step is involved in the catalytic cycle, controlling the structure (shape and size of the particles) and/or molar excess of the carbonate base used can significantly increase the reaction rate of Buchwald-Hartwig aminations. By taking such a "base effect" into account a general protocol for the intermolecular amination of aryl iodides with all types of amines has been developed based on a standard Pd-BINAP catalyst, using cesium carbonate as the base.

An efficient and cost-effective two-step synthesis of diaminopyridines, fundamental building blocks of biologically active compounds, is reported. The advantages over previously reported routes include cost and wider availability of the bromo-chloropyridine starting materials and the straightforward accessibility to an extended array of diaminopyridine regioisomers. The key enabler of this synthetic strategy is the development of an unprecedented palladium-catalyzed coupling reaction of ammonia with chloropyridines deactivated by the presence of an alkylamino substituent. The coupling reaction was accomplished with very low catalyst loadings under remarkably mild reaction conditions, making the system particularly suitable for both academic and industrial applications. The utility of this methodology is exemplified by the application to the synthesis of highly relevant scaffolds, including the synthetic intermediates of the marketed drugs Ribociclib and Palbociclib.

Secondary benzylic alcohols represent a challenging class of substrates for N-alkylation of amines. Herein, we describe an iron(II)-catalyzed eco-friendly protocol for N-alkylation of secondary arylamines with secondary benzyl alcohols through a carbocationic pathway instead of the known borrowing hydrogen transfer (BHT) approach. Transiently generated carbocations, produced from alcohols via self-condensation, were coupled with arylamines to provide highly functionalized amine products. The scope of this methodology involves N-alkylation of primary, secondary and heterocyclic amines with primary/secondary benzylic, allylic and heterocyclic alcohols, which are common key structures in numerous pharmaceuticals drugs. The method can also be easily adopted for the amination of various natural products. (Figure presented.).

We describe a most straightforward synthetic method for preparing neurokinin-1 (NK1) receptor antagonist derivatives by asymmetric hydrogenation of 3-amido-2-arylpyridinium salts using dinuclear iridium complexes with enantiopure diphosphine ligands, affo

A facile synthesis of imidazo[4,5-b]pyridines and-pyrazines is described using a Pd-catalyzed amide coupling reaction. This reaction provides quick access to products with substitution at N1 and C2. A model system relevant to the natural product pentosidi

An expedient, catalytic method for the synthesis of diverse azaindoles and indoles, starting from readily available and inexpensive starting materials, is described. Conditions were developed for effective reductive alkylation of electron-deficient o-chlo

An efficient regioselective method for the preparation of structurally diverse imidazopyridinones and benzoimidazolones starting from readily available and economical starting materials is described. High-yielding reductive alkylation of electron-deficient o-haloarylamines followed by treatment with inexpensive N-chlorosulfonyl isocyanate afforded primary ureas in good overall yields. A Pd-catalyzed urea cyclization reaction furnished imidazopyridinones and benzoimidazolones in excellent yields. Overall, the developed chemistry provides rapid access to pharmaceutically important heterocyclic compounds with high efficiency.

The general synthesis and a novel intramolecular nucleophilic aromatic substitution (SNAr) reaction of 2-carboxamido-3-arylquinazolin-4- ones, a potentially useful scaffold in the field of medicinal chemistry, are described. The synthetic utili

A novel intramolecular nucleophilic aromatic substitution reaction of 2-carboxamido-3-arylquinazolin-4-one derivatives induced by base treatment and its application to the expeditious synthesis of secondary aryl amines, including diaryl amines, are descri

A variete of N-alkyl-3-aryl-2-diphenylphosphinoyl-1H-pyridothiazines has been efficiently synthesized by treatment of the anion of 3-(N-alkyl-N-diphenylphosphinoylmethylamino)-2-chloro or -2,6-dichloropyridines with the appropriate aromatic O-