Conversion of Vicinal Halohydrins to Epoxides

The reaction, which is easy to carry out, is a stereospecific syn addition, and yields are usually high. 

Allylic alcohols are converted to epoxides by oxidation with ferf-butyl hydroperoxide in the presence of certain transition metals. The most significant aspect of this reaction— called the Sharpless epoxidation—is its high enantioselectivity when carried out using a combination of ferf-butyl hydroperoxide, titanium(IV) isopropoxide, and diethyl tartrate. 

Oxygen is transferred to the double bond of the allylic alcohol from the hydroperoxy group in a chiral environment and occurs enantioselectively. 

The value of this reaction was recognized with the award of the 2001 Nobel Prize in Chemistry to its creator K. Barry Sharpless. Sharpless epoxidation of allylic alcohols can be carried out with catalytic amounts of titanium(IV) isopropoxide and, because both enantiomers of diethyl tartrate are readily available, can be applied to the synthesis of either enantiomer of a desired epoxy alcohol. 

What would be the absolute configuration of the 2,3-epoxy-l-hexanol produced in the preceding reaction if diethyl (2S,3S)-tartrate were used instead of 2R,3R)7 

More than a laboratory synthesis. Sharpless epoxidation has been adapted to the large-scale preparation of (+)-disparlure, a sex pheromone used to control gypsy moth infestations, and of (/ )-glycidol, an intermediate in the synthesis of cardiac drugs known as beta-blockers. 

The following section describes the preparation of epoxides by the base-promoted ring closure of vicinal halohydrins. Because vicinal halohydrins are customarily prepared from alkenes (Section 6.17), both methods—epoxidation using peroxy acids and ring closure of halohydrins—are based on alkenes as the starting materials for preparing epoxides. 

The formation of vicinal halohydrins from alkenes was described in Section 6.17. Halohydrins are readily converted to epoxides on treatment with base  

Reaction with base brings the alcohol function of the halohydrin into equilibrium with its corresponding alkoxide  

in what amounts to an intramolecular Williamson ether synthesis, the alkoxide oxygen attacks the carbon that bears the halide leaving group, giving an epoxide. As in other nucleophilic substitutions, the nucleophile approaches carbon from the side opposite the bond to the leaving group  

Overall, the stereospecificity of this method is the same as that observed in per-oxy acid oxidation of alkenes. Substituents that are cis to each other in the alkene remain cis in the epoxide. This is because formation of the bromohydrin involves anti addition, and the ensuing intramolecular nucleophilic substitution reaction takes place with inversion of configuration at the carbon that bears the halide leaving group. 

Angle strain is the main source of strain in epoxides, but torsional strain that results from the eclipsing of bonds on adjacent carbons is also present. Both kinds of strain are relieved when a ring-opening reaction occurs. 

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