Design of New Ligands for the Palladium-Catalyzed Arylation of α-Branched Secondary Amines.

In Pd-catalyzed C-N cross-coupling reactions, α-branched secondary amines are difficult coupling partners and the desired products are often produced in low yields. In order to provide a robust method for accessing N-aryl α-branched tertiary amines, new catalysts have been designed to suppress undesired side reactions often encountered when these amine nucleophiles are used. These advances enabled the arylation of a wide array of sterically encumbered amines, highlighting the importance of rational ligand design in facilitating challenging Pd-catalyzed cross-coupling reactions.

Mild and highly selective palladium-catalyzed monoarylation of ammonia enabled by the use of bulky biarylphosphine ligands and palladacycle precatalysts.

A method for the Pd-catalyzed arylation of ammonia with a wide range of aryl and heteroaryl halides, including challenging five-membered heterocyclic substrates, is described. Excellent selectivity for monoarylation of ammonia to primary arylamines was achieved under mild conditions or at rt by the use of bulky biarylphosphine ligands (L6, L7, and L4) as well as their corresponding aminobiphenyl palladacycle precatalysts (3a, 3b, and 3c). As this process requires neither the use of a glovebox nor high pressures of ammonia, it should be widely applicable.

Dialkylbiaryl Phosphines in Pd-Catalyzed Amination: A User's Guide.

Dialkylbiaryl phosphines are a valuable class of ligand for Pd-catalyzed amination reactions and have been applied in a range of contexts. This review attempts to aid the reader in the selection of the best choice of reaction conditions and ligand of this class for the most commonly encountered and practically important substrate combinations.

Diamine Ligands in Copper-Catalyzed Reactions.

The utility of copper-mediated cross-coupling reactions has been significantly increased by the development of mild reaction conditions and the ability to employ catalytic amounts of copper. The use of diamine-based ligands has been important in these advances and in this review we discuss these systems, including the choice of reaction conditions and applications in the synthesis of pharmaceuticals, natural products and designed materials.

Biaryl phosphane ligands in palladium-catalyzed amination.

Palladium-catalyzed amination reactions of aryl halides have undergone rapid development in the last 12 years, largely driven by the implementation of new classes of ligands. Biaryl phosphanes have proven to provide especially active catalysts in this context. This Review discusses the application of these catalysts in C-N cross-coupling reactions in the synthesis of heterocycles and pharmaceuticals, in materials science, and in natural product synthesis.

Total synthesis of sanguiin H-5.

Using an atropdiastereoselective oxidative biaryl coupling as the key step, the total synthesis of the ellagitannin natural product sanguiin H-5 is reported. Both organomagnesium and organozinc based metalation methodologies were used to efficiently construct the strained medium-ring core of the natural product.

The oxidation of organocuprates--an offbeat strategy for synthesis.

The creation of carbon-carbon and carbon-heteroatom bonds by the oxidation of organocuprates is useful in a range of challenging contexts including the formation of biaryl bonds within medium rings, diene synthesis and the coupling of tertiary carbon centres. This tutorial review introduces these applications and recent developments which have served to improve its functional group tolerance and its utility in organic synthesis.

Aryl-aryl coupling via directed lithiation and oxidation.

Aryl lithium reagents formed by directed lithiation reactions undergo transmetallation with copper(I) salts to form organocuprates, which may be efficiently oxidized to yield ortho-substituted biaryls.