摘要：

The syn and anti isomers of axially chiral 1,8-diquinolylnaphthalenes have been synthesized via Pd-catalyzed Stille coupling of 1,8-dibromonaphthalene and 2-alkyl-4-trimethylstannylquinolines. Optimization of the cross-coupling reaction allowed the preparation of highly constrained 1,8-bis(2,2‘-dimethyl-4,4‘-diquinolyl)naphthalene, 2, and 1,8-bis(2,2‘-diisopropyl-4,4‘-diquinolyl)naphthalene, 3, in 42% and 41% yield, respectively. Employing Pd(PPh3)4 and CuO as the cocatalysts in the coupling reaction of 1,8-dibromonaphthalene and 2-alkyl-4-trimethylstannylquinolines proved to be superior over other catalysts such as PdCl2(dppf), Pd2(dba)3/P(t-Bu)3, and POPd. The C2-symmetric anti isomers of 2 and 3 were found to be more stable than the corresponding meso syn isomer. The ratio of the two enantiomeric anti conformers to the syn conformer was determined as 7.9:1 for 2 and 8.6:1 for 3 by NMR and HPLC analysis. The atropisomers of 2 and 3 were found to be stable to rotation about the chiral axis at room temperature and all three stereoisomers of 2 were isolated by semipreparative HPLC on a Chiralpak AD column. The diastereoisomers of 3 were separated via preferential crystallization of the anti isomers from diethyl ether. Slow syn/anti interconversion was observed for both atropisomers at enhanced temperature, and the diastereomerization and enantiomerization processes were monitored by NMR and HPLC. The Gibbs activation energy, ΔG, for the isomerization of 2 was determined as 116.0 (112.1) kJ/mol for the conversion of the anti (syn) to the syn (anti) isomer at 71.0 °C. The rotational energy barrier of 3 was determined as 115.2 (111.1) kJ/mol for the conversion of the anti (syn) to the syn (anti) isomer at 66.2 °C.

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