Transition State Studies on the Dioxirane-Mediated Asymmetric Epoxidation via Kinetic Resolution and Desymmetrization

Abstract

This paper describes an efficient kinetic resolution process of trisubstituted cyclic olefins via a chiral dioxirane generated in situ from a fructose-derived ketone and Oxone. The substrates presented include a variety of 1,3-disubstituted and 1,6-disubstituted cyclohexenes with the stereogenic centers at allylic positions. A sequential desymmetrization and kinetic resolution of 1,4-cyclohexadienes by the chiral dioxirane was also found to be feasible. The initially formed monoepoxides can be kinetically resolved by continuing the reaction, leading to the increase or decrease of the ee values of monoepoxides depending on the diene systems. In some cases, a prochiral directing group is not required and the first formed epoxide stereoselectively directs the second epoxidation. When the coupled desymmetrization and kinetic resolution is used synergistically, high enantiopurity can be obtained for an epoxide from an intrinsically less enantioselective substrate. The observed absolute and relative stereochemistry as well as the changing optical purity can be effectively rationalized by transition state analysis.

Synthetic methods : Part (ii) Oxidation and reduction methods

“…Further information regarding the reaction transition state has come from a study of kinetic resolution of trisubstituted cyclic alkenes. 24 Singleton has shown that experimental and calculated kinetic isotope effects for epoxidation by dioxiranes derived from chiral ketones are in good agreement, lending validity to the computational methods and providing new insights into the mode of asymmetric induction. 25 In particular, this study suggests that asynchronicity with regard to the formation of the two epoxide C-O bonds is a major consideration when developing transition state models.…”

Recent Advances in Organocatalytic Kinetic Resolution for the Synthesis of Functionalized Products

“…During organocatalysis development, Shi et al. observed sequential desymmetrization and kinetic resolution in dioxirane 94 ‐mediated asymmetric epoxidation of a variety of prochiral and symmetrical cyclic dienes 95 (Scheme ) . The desymmetrization process afforded monoepoxide 96 with 80 % ee , which was further enhanced to 98 % ee through subsequent KR by eliminating ent ‐ 96 from the nonracemic mixture.…”

Chiral recognition of ethers by NMR spectroscopy

“…Some prototypes of common polyether structures; polyglycols (8) and crown ethers (9) and cryptophanes (10). (13), 43 (1)-cis-lauthisan (14), 44 and laddered polyether natural products of marine origin, e.g., CTX-3C (15). or polyols (Scheme 3). Moreover, ethers and acetals can act as protecting groups in sugars.…”