Enantioselective Synthesis of Pyridines with All-Carbon Quaternary Carbon Centers via Cobalt-Catalyzed Desymmetric [2+2+2] Cycloaddition

A Co-catalyzed enantioselective desymmetric [2+2+2] cycloaddition for synthesis of pyridines with all-carbon quaternary carbon centers has been developed. The regio- and enantioselectivities are controlled by the inherent nature of terminal alkynes and the substituents on the bisoxazolinephosphine ligands. Pyridines with 5-substitutents could be obtained with >20:1 regioselectivity and up to 94 % ee when terminal alkyl, alkenyl or silyl alkynes and DTBM/Ph-based NPN* ligand L6 were used. Terminal aryl alkynes and Ph/Bn-based ligand L4 leads to formation of pyridines with 6-substitutents in up to 99 % ee.

Automated summary

A Co-catalyzed enantioselective desymmetric [2+2+2] cycloaddition has been developed for the synthesis of pyridines with all-carbon quaternary carbon centers, with regio- and enantioselectivities controlled by the nature of terminal alkynes and substituents on the bisoxazolinephosphine ligands. Pyridines with 5-substituents can be obtained with high regioselectivity and up to 94% ee, while pyridines with 6-substituents can be formed with up to 99% ee using different alkynes and ligands.