Chiral Recognition of Racemic Alcohols in Lattice Inclusion Compounds

Department of Material and Lifescience, Osaka University
â—‹Kazuaki Aburaya Ichiro Hisaki Norimitsu Tohnai Mikiji Miyata

Chiral recognition in inclusion crystals is of interest not only in resolution of racemate but also in crystal engineering and supramolecular chemistry. Though many artificial hosts have been developed for chiral recognition of alcohols in the crystalline state, there are few examples in which small alcohols have been included with high enantioselectivity [1]. Especially, in the case of secondary alcohols, it is difficult to recognize chirality due to the subtle structural differences between the enantiomers as implied by four-location model [2]. Bile acid derivatives include various alcohols within channel-like chiral cavities created by the host molecules. Therefore a systematic study of chiral recognition of secondary alcohols can be carried out.
We describe here chiral recognition of various alcohols in the inclusion compounds of bile acid derivatives such as 3-epicholic acid (ECA), 3-epideoxycholic acid (EDCA) and cholamide (CAM). The host compounds showed enantioselective inclusion for many aliphatic and aromatic alcohols. These enantioselctivity varied from poor to excellent depending on combination of a host and a guest. For example, crystallization of CAM from racemic 2,2-dimethyl-3-hexanol (1) showed selective inclusion of (S)-1 with as high as 98% enantiomeric excess (ee). On the other hand, crystallization of CAM from racemic 2-methyl-3-hexanol (2) showed inclusion of (S)-2 with 19% ee. The chiral recognition mechanism of these inclusion compounds will be examined on the basis of X-ray crystallographic analyses.
[1] Y. Imai, T. Sato, R. Kuroda Chem. Commun. 2005, 3289-3291. [2] K. Kato, K. Aburaya, Y. Miyake, K. Sada, N. Tohnai, M. Miyata Chem. Commun. 2003, 2872-2873.