Synthesis of C-Oligosaccharides via Ni-Catalyzed Reductive Hydroglycosylation.

C-Oligosaccharides are metabolically stable surrogates of native glycans containing O/N/S-glycosidic linkages and thus have therapeutic potential. Here we report a straightforward approach to the synthesis of vinyl C-linked oligosaccharides via the Ni-catalyzed reductive hydroglycosylation of alkynyl glycosides with glycosyl bromides.

Facile access to C-glycosyl amino acids and peptides via Ni-catalyzed reductive hydroglycosylation of alkynes.

C-Glycosyl peptides/proteins are metabolically stable mimics of the native glycopeptides/proteins bearing O/N-glycosidic linkages, and are thus of great therapeutical potential. Herein, we disclose a protocol for the syntheses of vinyl C-glycosyl amino acids and peptides, employing a nickel-catalyzed reductive hydroglycosylation reaction of alkyne derivatives of amino acids and peptides with common glycosyl bromides. It accommodates a wide scope of the coupling partners, including complex oligosaccharide and peptide substrates. The resultant vinyl C-glycosyl amino acids and peptides, which bear common O/N-protecting groups, are amenable to further transformations, including elongation of the peptide and saccharide chains.

Synthesis of Chiral Aldehyde Catalysts by Pd-Catalyzed Atroposelective C-H Naphthylation.

Chiral aldehyde catalysis opens new avenues for the activation of simple amines. However, the lack of easy access to structurally diverse chiral aldehyde catalysts has hampered the development of this cutting-edge field. Herein, we report a Pd-catalyzed atroposelective C-H naphthylation with 7-oxabenzonorbornadienes for the preparation of axially chiral biaryls with excellent enantioselectivities (up to >99 % ee). This reaction is scalable and robust, which serves as a key step to provide a rapid access to axially chiral aldehyde catalysts through a three-step C-H functionalization sequence. These chiral aldehydes exhibit better activities and enantioselectivities than the previously reported organocatalysts in the asymmetric activation of glycine derived amides and dipeptides. Moreover, preliminary investigation also discloses that the aldehyde catalyst can effectively override the intrinsic facial selectivity of chiral dipeptide substrates, showcasing the strong chiral induction ability of this type of novel aldehyde catalysts.

Pd-Catalyzed Atroposelective C-H Allylation through ß-O Elimination: Diverse Synthesis of Axially Chiral Biaryls.

Biaryl atropisomers are of great importance in natural products, pharmaceuticals, and asymmteric synthesis. The efficient synthesis of these chiral scaffolds with full enantiocontrol and high diversity remains challenging. Reported herein is a Pd-catalyzed atroposelective C-H allylation with tert-leucine as an efficient catalytic chiral transient auxiliary. A wide range of enantioenriched biaryl aldehydes were prepared in synthetically useful yields with excellent enantioselectivity (up to >99 % ee) through ß-O elimination. The reaction could be carried out on a gram scale without erosion of the ee value. A variety of axially chiral carboxylic acids could be obtained with high enantiopurity. The resulting axially chiral biaryl aldehydes and carboxylic acids might be used in asymmetric synthesis as chiral ligands and/or organocatalysts.