C3-Symmetric Cinchonine-Squaramide-Catalyzed Asymmetric Chlorolactonization of Styrene-Type Carboxylic Acids with 1,3-DichIoro-5,5-dimethyIhydantoin: An Efficient Method to Chiral Isochroman-1-ones

摘要

A more practical and efficient catalytic asymmetric chlorolactonization of styrene-type carboxylic acids with l,3-dichloro-5,5-dimethylhydan-toin (DCDMH) using C3-symmetric cinchonine-squaramide (CSCS) as organocatalyst has been developed. A series of chiral chloro-substituted iso-chroman-1-ones was obtained in excellent yields (up to 95%) and enantioselectivities (up to 99% ee), whwereby the results for chloro-substituted isochro-man-1-ones are the best ever achieved. The catalyst can be recovered and reused for six cycles. More-over, the chlorolactonization product 3b was further transformed to optically active bicyche isochroman-1-one derivatives in high yield without losing the enantioselectivity. Furthermore, compounds 3e and 2n proved to be highly potent inhibitors of the HIV-1 in TZM-bl cells.