Synthesis of Epoxides

Epoxides are easily made from alkenes, and (unlike other ethers) they undergo a variety of useful synthetic reactions. For these reasons, epoxides are valuable synthetic intermediates. Here we review the epoxidation techniques already covered (Section 8-12) and consider in more detail the useful syntheses and reactions of epoxides. 

Peroxyacids (sometimes called peracids) are used to convert alkenes to epoxides. If the reaction takes place in aqueous acid, the epoxide opens to a glycol. Therefore, to make an epoxide, we use a weakly acidic peroxyacid that is soluble in aprotic solvents such as CH2CI2. Because of its desirable solubility properties, me/a-chloroperoxyben-zoic acid (MCPBA) is often used for these epoxidations. 

The epoxidation takes place in a one-step, concerted reaction that maintains the stereochemistry of any substituents on the double bond. 

The peroxyacid epoxidation is quite general, with electron-rich double bonds reacting fastest. The following reactions are difficult transformations made possible by this selective, stereospecific epoxidation procedure. The second example uses magnesium monoperoxyphthalate (MMPP), a relatively stable water-soluble peroxyacid often used in large-scale epoxidations. 

A second synthesis of epoxides and other cyclic ethers involves a variation of the Williamson ether synthesis. If an alkoxide ion and a halogen atom are located in the same molecule, the alkoxide may displace a halide ion and form a ring. Treatment of a halohydrin with a base leads to an epoxide through this internal 5 2 attack. 

Ether Synthesis in Acidic Conditions, with Mercury Cation 

Epoxides are unique ethers that can be synthesized by oxidation of an alkene with a peroxyacid (RCO3H, such as mCPBA) or by an intramolecular Sn2 on a vicinal haloalcohol, called a halohydrin (this is an intramolecular version of 

We recall that epoxides can be synthesized by oxidizing an alkene (Section 9.8). The possible oxidizing agents are peroxyacetic acid (CHjCOsH), tw-chloroperoxy-benzoic acid (MCPBA). The epoxi-dation of alkenes with peroxy acids is stereospecific. The stereochemistry of the groups in the alkene remains cis groups in the alkene remain cis in the epoxide, and tram groups in the alkene remain 

A second method of synthesizing epoxides is an intramolecular variation of the Williamson ether synthesis. First, a halohydrin forms in the reaction of an alkene with an aqueous solution of a halogen. For example, chlorine gives a cyclic chloronium ion, which then reacts with water as the nucleophile to give the chlorohydrin. 

The chlorohydrin is treated with a base, producing an alkoxide ion that displaces a chloride ion from the adjacent carbon atom to form the epoxide ring. 

Draw the structure of the epoxide formed in the reaction of each of the following compounds with MMPP in ethanol. 

Write the halohydrin product of the electrophlhc addition of bromine in water to r-2-butene. What is the stereochemistry of the epoxide formed from this bromohydrin  

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Sulfonate Esters. Sucrose sulfonates are valuable intermediates for the synthesis of epoxides and derivatives containing halogens, nitrogen, and sulfur. In addition, the sulfonation reaction has been used to determine the relative reactivity of the hydroxyl groups in sucrose. The general order of reactivity in sucrose toward the esterification reaction is OH-6 OH-6 > OH-1 > HO-2. 

The synthesis of epoxides proceeds in the presence of a variety of functional groups and is also applicable to cyclo steroids. Halo epoxides, e.g, (45), can... 

Halohydrins are useful intermediates especially in the synthesis of epoxides The main reaction is usually accompanied by the formation of a dihalide... 

Stereoselective synthesis of epoxides andaziridines viaylide routes 99PAC369. 

Another method for the synthesis of epoxides is through the use of halo-hydrins, prepared by electrophilic addition of HO-X to alkenes (Section 7.3). When a halohydrin is treated with base, HX is eliminated and an epoxide is produced. 

Asymmetric Synthesis of Epoxides and Aziridines from Aldehydes and I mines... 

The aza-Darzens reaction is analogous to the Darzens synthesis of epoxides (see Section 1.2.3.2) but employs imines in the place of aldehydes (Scheme 1.27). 

When n-BuLi is used instead of t-BuLi, the byproduct after desulfinylation (n-BuS(O)Ph) possesses an acidic proton, which is abstracted by the metalated epoxide. Hence, overall, a stereoselective protodesulfmylation is achieved. This can be used for the asymmetric synthesis of epoxides, such as that of (-)-disparlure from enantiopure sulfoxide 222 (Scheme 5.53) [78]. 

The reaction between an aldehyde and a carbon nucleophile, such as a sulfur ylide, constitutes an alternative approach to the synthesis of epoxides. Since alkenes, which are the normal epoxidation substrates, are often formed from aldehydes, this approach can be highly efficient. On the other hand, the synthesis of appropriate carbon nucleophiles usually requires additional steps. 

The past thirty years have witnessed great advances in the selective synthesis of epoxides, and numerous regio-, chemo-, enantio-, and diastereoselective methods have been developed. Discovered in 1980, the Katsuki-Sharpless catalytic asymmetric epoxidation of allylic alcohols, in which a catalyst for the first time demonstrated both high selectivity and substrate promiscuity, was the first practical entry into the world of chiral 2,3-epoxy alcohols [10, 11]. Asymmetric catalysis of the epoxidation of unfunctionalized olefins through the use of Jacobsen s chiral [(sale-i i) Mi iln] [12] or Shi s chiral ketones [13] as oxidants is also well established. Catalytic asymmetric epoxidations have been comprehensively reviewed [14, 15]. 

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