Dielectrically Controlled Enantiomeric Resolution (DCR) of (<i>R</i>)- and (<i>S</i>)-2-Methylpyrrolidine by (<i>R</i>,<i>R</i>)-Tartaric Acid

Abstract

The molecular mechanism of dielectrically controlled resolution (DCR) observed in the resolution of ( RS )-2-methylpyrrolidine ( 1 ) by ( R, R )-tartaric acid ( 2 ) was studied. ( R )- 1 and ( S )- 1 were preferentially resolved from water/ethanol mixed solvents of different compositions with ε = 24.4 and 30, respectively. The X-ray analysis of two resolved salts, i.e., ( R )- 1:( R, R )- 2 and ( S )- 1:( R, R )- 2:H 2 O, was undertaken, and their crystal structures were compared in detail. The carboxyl groups of ( R, R )- 2 are engaged in strong negative-charge-assisted intermolecular hydrogen bonds, and ( R, R )- 2 forms similar layers in both crystal structures. The space between the layers in ( S )- 1:( R, R )- 2:H 2 O is larger than that in ( R )- 1:( R, R )- 2 . ( R )- 1 and ( S )- 1 are recognized in the chiral spaces formed between the layers of ( R, R )- 2 . Molecular mechanics calculations showed that the chiral spaces formed in the crystals ( S )- 1:( R, R )- 2 and ( R )- 1:( R, R )- 2 are more suitable to accommodate ( S )- 1 and ( R )- 1 than ( R )- 1 and ( S )- 1, respectively. The present study has strongly suggested that DCR is a common phenomenon.