Solvent-Dependent Self-Discrimination of Bis(2-hydroxyphenyl)diamides

Solvent-dependent, self-discrimination of diamides is described. Mixing a solution of (R)-1a and (S)-1a, which are valine-derived, bis(2-hydroxyphenyl)diamide-bearing, multiple hydrogen-bonding modules, in dichloromethane immediately led to the formation of a thick suspension comprising a 1:1 heterochiral aggregate of 1a. The solubility of heterochiral la was substantially lower in halogenated solvents than in ethyl acetate. A perusal of racemic crystal structures obtained from chloroform and ethyl acetate revealed a significant difference in the crystal-packing pattern, which is likely to be the basis for the pronounced difference in solubility. Specific self-discrimination of la in an ensemble of eight structurally related molecules showcased the specific aggregation through the hydrogen-bonding network of the bis(2-hydroxyphenyl)diamide framework. The low solubility of heterochiral la in halogenated solvent was exploited to achieve high stereoselectivity in a catalytic asymmetric reaction by using a low enantiomeric excess sample of la.