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.