Stereoselectivity of Enone Epoxidations With Alkaline Hydrogen Peroxide

Hamilton, Niall Morton (1989) Stereoselectivity of Enone Epoxidations With Alkaline Hydrogen Peroxide. PhD thesis, University of Glasgow.

Full text available as:
Download (6MB) | Preview


While stereoselective epoxidation of alkenes with a hydroxyl group using peracids or peroxides in conjunction with a catalyst has been well documented and feasible mechanisms proposed, the stereochemistry of epoxidation of enones with a-hydroxyl substituents using alkaline hydrogen peroxide is less well understood and perhaps deserves more detailed study. A thorough review of these methods for preparing epoxides from alkenes is covered in the introduction section of the thesis. Particular attention is paid to stereoselective epoxidations and the factors which influence stereoselectivity. Previous studies have shown that 4-hydroxy-4-methylnaphthalen-1(4H)-one (48) and l-hydroxy-l-isopropylnaphthalen-2(6H)-one (161) undergo stereospecific epoxidation with alkaline hydrogen peroxide to yield products in which the hydroxy and epoxy groups are cis and trans respectively. In an extension of these studies the synthesis of, a variety of cyclic enones substituted with a hydroxyl group was undertaken and the stereochemistry of the products examined after alkaline hydrogen peroxide epoxidation. Some structurally related enones in which there was no hydroxyl group but where another functionality was present were also similarly investigated. As had been established, alkaline epoxidation of the naphthalenone (48) gave exclusively the cis epoxy alcohol (49). It was shown that the stereospecificity of epoxidation was dependent on the alpha-hydroxyl group since both the methyl ether and methoxymethyl ether of (48) gave an almost equal mixture of both diastereomeric epoxides. Cleavage of the mixture of epoxy methoxymethyl ethers and separation of the resulting mixture of epoxy alcohols resulted in isolation of the previously unreported trans epoxy alcohol (247). An attempt to prepare a naphthalenone with a alpha-hydroxymethyl substituent for epoxidation studies was unsuccessful. To check that the directing affect of a alpha-hydroxyl group on alkaline epoxidation was not exclusive to naphthalenones a series of monocyclic p-quinols was prepared. Oxidation of p-cresol, 2,4-xylenol, mesitol, 2-t-butyl-4-methylphenol and 2,6-di-t-butyl-4-methylphenol with singlet oxygen generated in situ from cerie (IV) oxide and hydrogen peroxide, and reduction of the resulting hydroperoxides with dimethyl sulphide gave the p-quinols (268)-(272). Prolonged treatment of these dienones with alkaline hydrogen peroxide gave only the cis diepoxy alcohols in all cases except (270) (R1=R2=Me) which refused to react under these conditions. The stereochemistry of the diepoxide (295) was proved by x-ray crystallography. Regioselective monoepoxidation was achieved for the unsymmetrical p-quinol (271) (R1=H, R2=But). While a short exposure to alkaline hydrogen peroxide resulted in cis monoepoxidation of the non-substituted double bond, reaction with mcpba oxidised the substituted double bond. In contrast to the naphthalenone series alkaline epoxidation of 4-methoxy-4-methylcyclohexa-2,5-dienone afforded a single diepoxide. Nmr showed the epoxides were cis to one another but it was not possible to ascertain the stereochemistry of the epoxides relative to the alpha-ether substituent. To broaden the scope of the study and to try to establish whether other functional groups could effect stereospecific alkaline epoxidation of enones, a series of cyclohexenones which possessed both a hydroxyl group and carbonyl substituent in the a-position was prepared. Using a recently reported reaction, Hagemann's ester (308) was converted to the alpha-hydroxy enone (309) by stirring an ethyl acetate solution of the substrate with activated charcoal in the presence of air. The esters (308) and (309) proved to be versatile starting materials for investigating the epoxidation of a variety of alpha-substituted cyclohexenones. Unlike the naphthalenones and p-quinols these enones did not yield simple alpha,beta-epoxyketones on treatment with mcpba though an alternative peracid reagent, per-Amberlyst 15, proved effective for epoxidising alpha-hydroxy enones such as (309). In all cases the cis epoxy alcohol was the major epoxide isolated. Alkaline epoxidation of the alpha-hydroxy enone (309) was stereospecific affording the cis epoxy alcohol. Similar treatment of the corresponding methyl ester or N-phenyl amide (332) was also highly stereoselective though a small amount of the diastereomeric trans epoxy alcohol was formed. This stereoselectivity of epoxidation was lost on conversion of the alcohol (309) to its methoxymethyl ether, TBDMS ether or its acetate. In these cases both epoxides were formed in roughly equal proportions. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Organic chemistry
Date of Award: 1989
Depositing User: Enlighten Team
Unique ID: glathesis:1989-78013
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 30 Jan 2020 15:43
Last Modified: 30 Jan 2020 15:43

Actions (login required)

View Item View Item


Downloads per month over past year