Synthesis of Naphthylpyridines from Unsymmetrical Naphthylheptadiynes and the Configurational Stability of the Biaryl Axis

A series of different unsymmetrically substituted naphthyl-based diynes were synthesized. These substrates formed the foundation for the assembly of novel biaryls containing pyridine moieties with differently substituted five-membered rings in the backbone of the newly formed heterobiaryl system. The key step for their efficient construction was the photo- and cobalt-catalyzed [2 + 2 + 2] cycloaddition reaction between the corresponding naphthyldiyne and aceto- or benzonitrile. The heterobiaryl products have been isolated and investigated with respect to the configurational stability of their biaryl axis using dynamic chiral HPLC; subtle effects of the substitution pattern on the stability of the axis were observed. For several compounds the activation barriers (ΔG ‡) of racemization were determined. Suitable substitution of the five-membered ring backbone exemplarily allowed the Co-catalyzed enantioselective cyclization to yield the enantiomerically enriched heterobiaryl.