Epoxide

An epoxide is a cyclic ether with three ring atoms. These rings approximately define an equilateral triangle, which makes it highly strained. The strained ring makes epoxides more reactive than other ethers.

Quotes

• Epoxides (oxiranes) are widely used as versatile synthetic intermediates because regio- and stereoselective methods exist both for their construction and subsequent reactions. Reactions of epoxides are dominated by the electrophilic nature of the strained three-membered ring, which is susceptible to attack by a variety of nucleophiles. … The reaction of alkenes with peroxy acids provides for convenient and selective oxidation of double bonds. … Epoxidation involves an electrophilic syn-addition of the oxygen moiety of the peroxy acid to the double bond. The concerted formation of two new C-O bonds ensures that the reaction is stereospecific: cis-alkenes furnish the corresponding cis-epoxides and trans-alkenes the corresponding trans-isomers (racemic).
  • George S. Zweifel and Michael H. Nantz, Modern Organic Synthesis (2006), Ch. 5 : Functional Group Transformations: The Chemistry of Carbon-Carbon π-Bonds and Related Reactions
• Oxidation of α,β-unsaturated ketones with alkaline hydrogen peroxide produces the corresponding keto epoxides in good yields. This nucleophilic epoxidation proceeds via an initial Michael-type addition of the hydroperoxide anion to the enone system … Treatment of enones with basic tert-butyl hydroperoxide provides an alternative route for epoxidation of enones when the alkaline hydrogen peroxide procedure fails.
  • George S. Zweifel and Michael H. Nantz, Modern Organic Synthesis (2006), Ch. 5 : Functional Group Transformations: The Chemistry of Carbon-Carbon π-Bonds and Related Reactions

• Dirnethyldioxirane (DMDO) is a mild reagent for epoxidation under neutral conditions of electron-rich as well as of electron-deficient alkenes. Moreover, dimethyldioxirane is often the oxidant of choice for the preparation of labile epoxides. … Methyl(trifluoromethyl)dioxirane (TFDO), … is more reactive than DMDO by a factor of ~600. … TFDO can be used to regioselectively oxidize tertiary over secondary C-H bonds via an “oxenoid” (butterfly) mechanism.
  • George S. Zweifel and Michael H. Nantz, Modern Organic Synthesis (2006), Ch. 5 : Functional Group Transformations: The Chemistry of Carbon-Carbon π-Bonds and Related Reactions

• The reaction of chloro- or bromohydrins with bases provides an economical route for the preparation of epoxides. Halohydrins are readily accessible by treatment of an alkene with either hypochlorous acid (Cl₂ + H₂O → HOCl), hypochlorite bleach solution (NaOCl), or hypobromous acid (NBS + H₂O → HOBr). These reactions involve the initial formation of a halohydrin via anti-addition of X⁺ and HO^-, followed by internal "S_N2" displacement of the halide by the oxyanion.
  • George S. Zweifel and Michael H. Nantz, Modern Organic Synthesis (2006), Ch. 5 : Functional Group Transformations: The Chemistry of Carbon-Carbon π-Bonds and Related Reactions

• Chloroiodomethane on treatment with methyllithium-lithium bromide or n-butyllithium at low temperature undergoes lithium iodide exchange to form a lithium chlorocarbenoid species [LiCH₂Cl]. This highly reactive "carbanion" intermediate can be intercepted by the carbonyl group of aldehydes or ketones before it undergoes α-elimination to generate carbene and LiC1. Displacement of chloride from the initially formed carbonyl adducts furnishes the corresponding epoxides in high yields.
  • George S. Zweifel and Michael H. Nantz, Modern Organic Synthesis (2006), Ch. 5 : Functional Group Transformations: The Chemistry of Carbon-Carbon π-Bonds and Related Reactions

• The inherent strain (-27 kcal/mol) of epoxides makes them prone to (1) ring opening by a wide range of nucleophiles, (2) base-induced rearrangement, and (3) acid-catalyzed isomerization. … Generally, nucleophilic opening of an unsymmetrically substituted epoxide is regioselective. … . In cyclohexane derivatives, opening of the epoxide ring with nucleophilic reagents proceeds stereospecifically in the majority of cases via an S,2 reaction, placing the oxygen of the epoxide and the attacking nucleophile in a trans- and diaxial-relationship. Thus, a single diastereomer of an epoxide gives upon ring opening a single diastereomer of the product.
  • George S. Zweifel and Michael H. Nantz, Modern Organic Synthesis (2006), Ch. 5 : Functional Group Transformations: The Chemistry of Carbon-Carbon π-Bonds and Related Reactions

• Although epoxidation of cyclic alkenes occurs preferentially from the less hindered side, the presence of a polar substituent near the double bond may reverse the facial direction of attack by the peroxide.
  • George S. Zweifel and Michael H. Nantz, Modern Organic Synthesis (2006), Ch. 5 : Functional Group Transformations: The Chemistry of Carbon-Carbon π-Bonds and Related Reactions

• Straight-chain allylic alcohols have been crucial to the development of stereoselective syntheses of complex natural products since they can be converted stereoselectively into epoxides and via further elaboration of these into a host of functionalized compounds of predictable stereochemistry.
  • George S. Zweifel and Michael H. Nantz, Modern Organic Synthesis (2006), Ch. 5 : Functional Group Transformations: The Chemistry of Carbon-Carbon π-Bonds and Related Reactions