Design, synthesis, and screening of chiral binaphthyl ketones for catalytic asymmetric epoxidation of alkenes
Stearman, Chad J.
Doctor of Philosophy
Research directed toward the design, synthesis, and screening of binaphthyl ketones for catalytic asymmetric epoxidation of alkenes is reported. To date, an easily accessible and recyclable catalyst that tolerates a wide structural variety of unfunctionalized alkenes has not been developed. It has been discovered that fluorinated chiral binaphthyl ketones catalyze the asymmetric epoxidation of alkenes with a high degree of enantiocontrol. A series of five binaphthyl ketone catalysts with variable distribution of fluorine atoms alpha to the carbonyl were synthesized. These catalysts were screened in the asymmetric epoxidation of trans-beta-methyl styrene. A trend of epoxidation efficiency as a function of alpha fluorination was revealed. Although, several of these catalysts performed well in the screening process, the most accessible was an alpha-fluorinated binaphthyl ketone. This ketone epoxidized trans-beta-methylstyrene to trans-beta-methylstyrene oxide with 57% conversion in 80% enantioselectivity. In order to improve conversion and enantioselectivity with this catalyst, a study of the various reaction parameters such as pH, organic cosolvent, and the amount of primary oxidant used was undertaken. During this study a significant dependence on these parameters was revealed, particularly, that of the organic cosolvent. Optimization of these conditions has led to dramatic improvements in the epoxidation efficiency of alpha-fluorinated binaphthyl ketone. This efficiency is highlighted in the epoxidation of trans -beta-methylstyrene to trans-beta-methylstyrene oxide with 100% conversion and 94% ee (from 57% conversion and 80% ee). Moreover, a substrate study suggests the optimized solvent allows for a pi-stack interaction which contributes to high enantioselectivity and conversions for both 1,1-disubstituted and terminal alkenes.