Epoxidation leaving groups

Next 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 m other nucleophilic substitutions the nucleophile approaches carbon from the side oppo site the bond to the leaving group... 

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

R Cu, or litliium or magnesium homocuprates RfCuM fM = Li, MgX), are fre-quently used, but a number of catalytic processes have also been developed. These processes nornnally utilize a catalytic amount of a copper salt CuY and a stoichiometric amount of an organometallic reagent R M IM = Li, MgX, ZnX, etc.). Hie leaving groups used include balides, esters, sulfonates, and epoxides, among others. 

Unlike other ethers, epoxide rings con be cleaved by base as well as by acid. Although an ether oxygen is normally a poor leaving group in an reaction (Section 11.3), the strain of the three-membered ring causes epoxides to react with hydroxide ion at elevated temperatures. 

It was demonstrated that when a better leaving group than lithium oxide (Li20) is present at the a-position (e. g., epoxide 125 Scheme 5.27), alkene formation occurs with retention of the alcohol moiety [44]. 

When a better leaving group than LiNSC R (e.g., OMe) is present at the a-position, retention of the potentially useful sulfonamide moiety occurs (e. g., in the conversion of aziridine 271 into the highly functionalized amino ether 272 Scheme 5.69) [98]. It should be noted that the analogous chemistry with epoxides of allylic diethers failed this could again (see above) be possibly due to the higher pKa of the epoxide proton relative to the aziridine proton. 

Another circumstance that increases leaving-group power is ring strain. Ordinary ethers do not cleave at all and protonated ethers only under strenuous conditions, but epoxides are cleaved quite easily and protonated epoxides even more easily. Aziridines and episulfides, three-membered rings containing, respectively, nitrogen and sulfur, are also easily cleaved (see p. 458). ... 

Other leaving groups are sometimes used. Sulfates, sulfonates, and epoxides give the expected products. Acetals can behave as substrates, one OR group being replaced by ZCHZ in a reaction similar to 10-101. Ortho esters behave similarly, but the product loses R OH to give an enol ether. ... 

Answer The required disconnection is (13a) which clearly needs optically active epoxide (15). This must be made from (14) without inverting the chiral centre so reduction of the COgEt group and conversion to a leaving group are needed. 

Whereas phosphonium ylides normally react with carbonyl compounds to give alkenes, dimethylsulfonium methylide and dimethylsulfoxonium methylide yield epoxides. Instead of a four-center elimination, the adducts from the sulfur ylides undergo intramolecular displacement of the sulfur substituent by oxygen. In this reaction, the sulfur substituent serves both to promote anion formation and as the leaving group. 

Acid catalysis assists epoxide ring opening by providing a better leaving group (an alcohol) at the carbon atom undergoing nucleophilic attack. 

The synthetic equivalents of the carbocations can be, of course a carbonyl group or a carbon with a leaving group -X, an epoxide or an activated double bound. 

Epoxides bearing a leaving group in a suitable position, such as chloromethyl epoxides, react with sodium telluride (prepared by the Rongalite method), giving allyhc alcohols. ... 

---