Synthesis of Chiral Piperazines via Hydrogenation of Pyrazines Activated by Alkyl Halides.

A facile method has been developed for the synthesis of chiral piperazines through Ir-catalyzed hydrogenation of pyrazines activated by alkyl halides, giving a wide range of chiral piperazines including 3-substituted as well as 2,3- and 3,5-disubstituted ones with up to 96% ee. The high enantioselectivity, easy scalability, and concise drug synthesis demonstrate the practical utility.

Enantioselective palladium-catalyzed C-H functionalization of indoles using an axially chiral 2,2'-bipyridine ligand.

A palladium-catalyzed enantioselective CH functionalization of indoles was achieved with an axially chiral 2,2'-bipyridine ligand, thus providing the desired indol-3-acetate derivatives with up to 98 % ee. Moreover, the reaction protocol was also effective for asymmetric OH insertion reaction of phenols using α-aryl-α-diazoacetates. This represents the first successful application of bipyridine ligands with axial chirality in palladium-catalyzed carbene migratory insertion reactions.

Iridium-catalyzed selective hydrogenation of 3-hydroxypyridinium salts: a facile synthesis of piperidin-3-ones.

The selective hydrogenation of 3-hydroxypyridinium salts has been achieved using a homogeneous iridium catalyst, providing a direct access to 2- and 4-substituted piperidin-3-one derivatives with high yields, which are important organic synthetic intermediates and the prevalent structural motifs in pharmaceutical agents. Mild reaction conditions, high chemoselectivity, and easy scalability make this reaction highly practical for the synthesis of piperidin-3-ones.

Formal palladium-catalyzed asymmetric hydrogenolysis of racemic N-sulfonyloxaziridines.

Highly enantioselective palladium-catalyzed formal hydrogenolysis of racemic N-sulfonyloxaziridines has been realized, providing a novel access to sultams with up to 99% ee. Preliminary mechanistic insights revealed that the reaction proceeded through a N-O bond cleavage, dehydration, and the sequential asymmetric hydrogenation.

Asymmetric hydrogenation via capture of active intermediates generated from aza-Pinacol rearrangement.

An efficient palladium-catalyzed asymmetric hydrogenation via capture of an active intermediate generated in situ from acid-catalyzed aza-Pinacol rearrangement has been successfully developed, providing efficient access to chiral exocyclic amines with up to 98% ee. Three-, four-, and five-membered cyclic N-sulfonyl amino alcohols are viable substrates. This study opens a new window to the application of asymmetric hydrogenation.

Palladium-catalyzed asymmetric hydrogenation of 3-phthalimido substituted quinolines.

Homogeneous Pd-catalyzed asymmetric hydrogenation of 3-phthalimido substituted quinolines was successfully developed, providing facile access to chiral substituted tetrahydroquinolines bearing two contiguous stereogenic centers with up to 90% ee.

Iridium-catalyzed asymmetric hydrogenation of pyrrolo[1,2-a]pyrazinium salts.

Highly enantioselective iridium-catalyzed hydrogenation of pyrrolo[1,2-a]pyrazinium salts has been achieved, providing a direct access to chiral 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine derivatives with up to 95% ee. The key feature of the reaction is the addition of cesium carbonate, which increases the conversion and prohibits the racemization pathway of products.