Stereochemical Stability Differences between Axially Chiral 6-Aryl-Substituted Picolinic Esters and Their Benzoic Ester Derivatives: sp2N: vs. sp2CH in CH3, C6H5, and CH3O ortho-Substitution Effect

Abstract

Abstract An axially chiral naphthyl-substituted picolinic acid (R-Naph-PyCOOH) or its allyl ester (R-Naph-PyCOOAll) acts as an excellent ligand for catalytic asymmetric dehydrative intramolecular allylation. Towards the future development of a high performance catalysis using R-Naph-PyCOOH or its carba-analogue (R-Naph-PhCOOH), the stereochemical stability of R-Naph-PyCOOAll and R-Naph-PhCOOAll has been investigated by a systematic change in the ortho-substituent R on the naphthalene ring from CH3 to C6H5 and CH3O to provide a range of effective radius (ER) and Hammett standard σ constant (σp). Enantiomerically pure R-Naph-PyCOOAll and R-Naph-PhCOOAll were prepared, and the rotational energy barriers ΔG‡(sp2N) and ΔG‡(sp2CH) as well as the racemization half-life (t1/2) were determined by time-interval chiral HPLC analysis of the enantiomer ratio (er). These experiments revealed have been i) that replacement of sp2CH with sp2N lowers ΔG‡ at least by 14 kJ mol−1 (3.3 kcal mol−1), and ii) that the degree of the ΔG‡ lowering (ΔΔG‡) is not proportional to ER, but has a high linear correlation to σp with a negative ρ value. In this particular system, a synergistic effect of the steric and electronic factors stabilizes TSφ180 with a 180° dihedral angle of CH3OC(2′)=C(1′)–C(6)=N(1) over TSφ0, decreasing the t1/2 of CH3O-Naph-PyCOOAll to 7 days from 1600 years of CH3-Naph-PyCOOAll.