Structural Probing of Ketone Catalysts for Asymmetric Epoxidation

Abstract

A series of chiral ketones derived from carbohydrates were investigated as catalysts for the asymmetric epoxidation. Fructose-derived ketones are found to be efficient catalysts. The studies show that the structural requirements for the ketone catalysts are very stringent and different types of olefins may require ketones with different structural arrangements. The current study allows us to further understand the chiral ketone catalyzed asymmetric epoxidation and provides some insight for the development of new catalysts.Dioxiranes are remarkably versatile oxidizing agents which show encouraging potential for asymmetric synthesis, particularly asymmetric epoxidation. Dioxiranes can be generated in situ from Oxone (potassium peroxomonosulfate) and ketones. 1,2 In principle, only a catalytic amount of ketone is required, so with a chiral ketone there exist opportunities for catalytic asymmetric epoxidation. 3,4 Since the pioneering work reported by Curci in 1984, 3a this area has received intensive interest.However, discovering efficient chiral ketone catalysts has proven to be a challenging problem.In the search for efficient ketone catalysts for asymmetric epoxidation, both reactivity and selectivity are crucial issues to be considered. Scheme 1 shows a number of possible pathways involved in the catalytic cycle of the ketone mediated epoxidation. Achieving the desired outcome from this deceivingly simple looking reaction requires a delicate balance among all the possible pathways (a-k). 5 Intuitively speaking, high enantioselectivity is more likely to be achieved when the stereogenic centers are closer to the reacting center (carbonyl group) due to more efficient stereochemical communication between substrate and catalyst. 6 A potential problem associated with this type of ketone is the possible racemization of the chiral centers due to the acidity of the protons at R positions (path e in Scheme 1), which puts restrictions on the choice of groups.Aside from the epimerization problem, the steric and electronic properties of the substituents are also extremely important for the reaction. If R 1 and R 2 are too large, the formation of tetrahedral intermediate II and/ or dioxirane IV will be retarded. As a result, Oxone can decompose nonproductively via pathway g. The steric hindrance of R 1 and R 2 could also slow the reaction between dioxirane IV and the olefin, which would result in undesired consumption of the dioxirane via pathway i and/or j (many dioxiranes are short-lived). 7 On the other hand, if R 1 and R 2 are too small, the stereochemical communication between the olefin and the chiral centers For examples of in situ generation of dioxiranes see: (a) Edwards, J. O.; Pater, R. H.; Curci, R.; Di Furia, F. Photochem. Photobiol. 1979, 30, 63. (b) Curci, R.; Fiorentino, M.; Troisi, L.; Edwards, J. O.; Pater, R. H. For leading references on asymmetric epoxidation mediated by chiral ketones see: (a) Curci, R.; Fiorentino, M.; Serio, M. R. J. Chem. Soc., Chem. Commun. 1984, 155. (b) Curci, R.; D'Accolti, L.; Fio...

Novel asymmetric oxy‐michael addition reaction of the chiral ketones to the achiral γ‐ or δ‐hydroxy‐α,β‐unsaturated carbonyl compounds

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Recent Advances in Iminium‐Salt‐Catalysed Asymmetric Epoxidation

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