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

Abstract

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.

Recent trends and applications in liquid‐phase chromatography enantioseparation of atropisomers

“…Hapke and co‐workers synthesized a series of naphthyl‐based pyridines with differently substituted annulated five‐membered ring systems . The obtained heterobiaryl racemates were investigated in terms of configurational stability of newly formed stereogenic biaryl axis (Fig.…”

“…Activation barrier values obtained by DHPLC for five‐membered backbones with different neighboring groups .…”

Transition‐Metal‐Mediated/Catalyzed Synthesis of Pyridines, Pyrimidines, and Triazines by [2+2+2] Cycloaddition Reactions

“…Hapke group also demonstrated catalytic activities various Co-catalyzed asymmetric [2 + 2 + 2] cycloaddition. [16] The photo-chemical cycloaddition of the diynes and nitriles catalyzed by [CpCo(cod)] was found to serve as an efficient synthetic route to the construction of the heterobiaryls (Scheme 15a). The use of [CpCo(trans-MeO 2 CHC=CHCO 2 Me){P(OEt) 3 }] under microwave conditions were shown to be effective to the access of 39 (Scheme 15b).…”

Three atropisomers of biphenyl: twist by tunable para substituents

“…The tunable dihedral or twist angle (φ) of biphenyl derivatives have garnered long-standing attention due to their potential application in molecular electronics [1][2][3] and catalytic transformations. 4 As shown in Scheme 1, the biphenyl is known to exist from 45 • to 90 • twist angle in the gaseous state due to ortho substituent repulsion, 5,6 while the biphenyl appears to be planar in the crystalline state at room temperature due to π-electron delocalization. 7,8 It is clear that the controlled tunability of biphenyl ring by suitable substituent is paramount, 9 as these characteristics are key to adapting the unique structural and electronic demands of materials.…”