engleski

INVERSION OF ENANTIOSELECTIVITY DISENTANGLED: ONE CATALYST FOR BOTH ENANTIOMERS IN CINCHONA-MEDIATED DESYMMETRIZATION OF GLUTARIC MESO-ANHYDRIDES

A puzzling inversion of enantioselectivity dependent on catalyst loading was observed during the quinine mediated desymmetrization of glutaric meso-anhydrides1. The novel catalytic protocol utilizing 0.1 eq of alkaloid and xanthene-9-carboxylic acid at room temperature (RT) was found comparable to the protocol requiring 1.1 eq of alkaloid at -30°C in the formal syntheses of the sample pharmacological compounds. The option of using a single catalyst, to obtain the one as well as the another enantiomer in excess was found the most intriguing, especially comprehending that the unmodified and cheap catalyst was used. Computational study of the molecular interactions was also performed to give an insight into the mechanistic background. Alcohol and the anhydride were found directly hydrogen bonded to the catalyst, while acid was upon addition found to intercalate between the alcohol and quinine. The net result was that the alcohol approached the anhydride from the opposite face, in agreement with the observed inversion of enantioselectivity. (1) Ivšić, T. ; Hameršak, Z. Tetrahedron: Asymmetry 2009, 20, 1095–1098.

Desymmetrization; Enantioselectivity; Density functional calculations; Asymmetric synthesis; Hydrogen bonding

nije evidentirano