Synthesis, Properties, and Enantiomerization Behavior of Axially Chiral Phenolic Derivatives of 8-(Naphth-1-yl)quinoline and Comparison to 7,7′-Dihydroxy-8,8′-biquinolyl and 1,1′-Bi-2-naphthol

Abstract An aza-analogue of 1,1′-bi-2-naphthol (BINOL, 3 ), 7-hydroxy-8-(2-hydroxynaphth-1-yl)quinoline (8-azaBINOL, 2 ), was prepared in 3 steps and 49% yield from N , N -diethyl O -(7-hydroxy-8-iodoquinolyl)carbamate via Suzuki coupling with 1-naphthylboronic acid followed by Sanford oxidation and saponification. 8-AzaBINOL ( 2 ) was resolved into (–)-( aS ) and (+)-( aR ) atropisomers via enzymatic hydrolysis of its racemic divalerate derivative with bovine pancreas acetone powder. The configurational stability of diol 2 was found to be intermediate to that of 7,7′-dihydroxy-8,8′-biquinolyl (8,8′-diazaBINOL, 1 , least stable) and BINOL ( 3 , most stable). Eyring plot analysis of the enantiomerization kinetics of 1 , 2 , and 3 , in DMSO solution revealed activation parameters of ΔH ‡ = +27.4, +19.9, +23.2 kcal mol –1 , and ΔS ‡ = +3.8, –27.9, –25.3 cal mol –1 K –1 , respectively. The unique character of ΔH ‡ and ΔS ‡ values for biquinolyl 1 suggests that the enantiomerization mechanism for 1 is distinct to that for naphthalenes 2 and 3 . Monohydroxy analogues of 2 , 7-hydroxy-8-(naphth-1-yl)quinoline ( 7 ) and 8-(2-hydroxynaphth-1-yl)quinoline ( 8 ), were similarly prepared and their racemization half-lives at room temperature were determined; τ 1/2(rac) was strongly dependent on solvent for naphthol 8 [ τ 1/2(rac) at 24 °C: in CHCl 3 = 2.7 h, in MeOH = 89 h] but not for the quinol 7 [ τ 1/2(rac) at 24 °C: in CHCl 3 = 106 h, in MeOH = 120 h].