Copper(ii)-mediated resolution of α-halo carboxylic acids with chiral O,O′-dibenzoyltartaric acid: spontaneous racemization and crystallization-induced dynamic resolution

Abstract

Herein we present a new example of coordination-mediated resolution of racemic acids by a chiral acid. The reaction of copper(II) acetate monohydrate, optically pure O,O′-dibenzoyltartaric acid (DBTA) and racemic α-bromo-2-chlorophenylacetic acid (HL¹) in acetonitrile solution afforded a binuclear copper(II) complex with D-DBTA dianion, α-bromo-2-chlorophenylacetate and acetate as ligands. After decomposition of the complex with acid, the optically active acid ((R)–HL¹) was obtained. Similarly, α-bromo-2-fluorophenylacetic acid (HL²), α-bromo-2-bromophenylacetic acid (HL³), α-chloro-2-chlorophenylacetic acid (HL⁴), α-chloro-2-fluorophenylacetic acid (HL⁵), α-bromophenylacetic acid (HL⁶), α-bromo-4-chlorophenylacetic acid (HL⁷), 2-bromopropionic acid (HL⁸) and 2-chloropropionic acid (HL⁹) were resolved by the same method. Satisfactory results were obtained for HL² to HL⁵. For HL⁶ and HL⁷, only racemic acids were obtained. For the two α-halo aliphatic acids (HL⁸ and HL⁹), poor enantioselectivity was obtained. It is more interesting that three acids (HL¹, HL² and HL³) could spontaneously racemize in acetonitrile solution, which resulted in crystallization-induced dynamic resolution (CIDR) with greater than 50% yield.