**2. Generation and amplification of chirality by crystallization**

Optically active molecules must crystallize into chiral space groups, but a racemic mixture in solution may either aggregate to form a nonchiral racemic crystal or undergo a spontaneous resolution where the two enantiomers segregate into a conglomerate of enantiopure crystals. Achiral molecules may crystallize into either a nonchiral or a chiral space group. If they crystallize into a chiral space group, the achiral molecules reside in a chiral environment imposed by the lattice. Most achiral molecules are known to adopt interconverting chiral conformations in fluid media, which could lead to a unique conformation upon crystallization. Crystals that have chiral space groups are characterized by being enantiomorphous. They exist in right-handed and left-handed forms that may or may not be visually distinguishable. In spite of impressive work on crystal engineering, predictions on a correlation between crystal symmetry and molecular structures are still hard to make.12)

Chiral crystals, like any other asymmetric object, exist in two enantiomorphous equienergetic forms, but careful crystallization of the material can induce the entire ensemble of molecules to aggregate into one crystal, of one-handedness, presumably starting from a single nucleus (Figure 3). However, it is not uncommon to find both enantiomorphs present in a given batch of crystals from the same recrystallization.

For achieving asymmetric synthesis, we should begin with a compound crystallizing in any one of the chiral space groups. Of the 230 distinct space groups, the most commonly occurring are *P*21/c, *P*-1, *P*212121, *P*21, *C*2/c, and *P*bca, the chiral ones being *P*212121, *P*21, *P*1 and *C*2.13)

The asymmetric crystallization of achiral compounds is stimulated by autoseeding with the first crystal formed. Although the chiral sense of the spontaneously formed chiral crystals cannot be predicted, seed crystals of the preferred chirality can be added in a more practical procedure to obtain one enantiomorph of a crystal.

Fig. 3. Chiral crystallization with fast enantiomerization
