Enantiomeric Inclusion of α-Hydroxy Esters by (R)-(1-Naphthyl)glycyl-(R)-phenylglycine and the Crystal Structures of the Inclusion Cavities

A simple dipeptide, ( R )-(1-naphthyl)glycyl-( R )-phenylglycine [( R, R )- 1 ], formed inclusion compounds with several α-hydroxy esters ( 2 ) with high enantioselectivity. By crystallization of a mixture of the dipeptide [( R, R )- 1 ] and racemic 2a [MeCH(OH)COOMe] from methanol, asymmetric recognition occurred to give an inclusion compound that contains the S form of 2a in 89% ee. X-ray crystallographic study of the inclusion compound elucidated that the dipeptide molecules arrange in a “folded antiparallel” β-sheetlike structure to accommodate the α-hydroxy ester in the pocket-type cavity surrounded by naphthyl and phenyl groups on the sheet. Similarly, 2b [MeCH(OH)COOEt] and 2f [dihydro-3-hydroxy-4,4-dimethyl-2(3 H )-furanone] were included with high enantioselectivity of the S form. When bulkier 2l [ t- BuCH(OH)COOMe] was used as a guest molecule, the arrangement of dipeptide molecules changed to an “extended antiparallel” mode, where the naphthyl and phenyl groups arranged in a “parallel stacked and displaced” mode and a channel-type cavity was constructed. The guest molecules were accommodated via hydrogen bonding in the channel-type cavity with high enantioselectivity of the S form (82% ee). In the case of 2k [ i -PrCH(OH)COOMe], optically pure ( S )- 2k formed the dipeptide sheet with the “folded antiparallel” structure by cocrystallization with ( R, R )- 1, while the “extended antiparallel” structure appeared in the inclusion of racemic 2k .