Handedness Determination of 2<sub>1</sub> Helical Motifs and Hierarchical Analysis of Crystal Structures Based on the Motifs: The Case of Cinchona Alkaloid Derivatives

A molecular assembly with a two-fold screw axis, a so-called 2<sub>1</sub> helical assembly, is one of the most fundamental and important motifs of organic noncentrosymmetric crystals. 2<sub>1</sub> Helical assemblies are observed frequently in the crystals of Cinchona alkaloids, crucial compounds for asymmetric organic syntheses. Despite of importance of their superstructures, there are no reports about the handedness of 2<sub>1</sub> helical assemblies. In this study, we revealed crystal structures of BH<sub>3</sub> complexes with a series of Cinchona alkaloids: cinchonidine, quinine, hydroquinine, cinchonine, quinidine, and hydroquinidine (Cnd·BH<sub>3</sub>, Qn·BH<sub>3</sub>, HyQn·BH<sub>3</sub>, Cnn·BH<sub>3</sub>, Qd·BH<sub>3</sub>, and HyQd·BH<sub>3</sub>, respectively), and we first defined the handedness of 2<sub>1</sub> helical assemblies of Cinchona alkaloids on the basis of a supramolecular-tilt-chirality method we have proposed. Interestingly, in crystalline states, Qn·BH<sub>3</sub> and HyQn·BH<sub>3</sub> form 3<sub>2</sub> helical motifs, while Cnd·BH<sub>3</sub> forms a left-handed 2<sub>1</sub> motif and Cnn·BH<sub>3</sub>, Qd·BH<sub>3</sub>, and HyQd·BH<sub>3</sub> form right-handed 2<sub>1</sub> helices despite their similar O−H···N intermolecular hydrogen bonds. Therefore, this set of these structures, which is the first example of crystal structures obtained for a series of Cinchona alkaloids or their derivatives chemically modified in the same way, enables us to elucidate a chiral relationship between molecular structures and supramolecular assembly manners.