Acid-Catalyzed Opening of Epoxides

Most epoxides are easily isolated as stable products if the solution is not too acidic. Any moderately strong acid protonates the epoxide, however. Water attacks the proto-nated epoxide, opening the ring and forming a 1,2-diol, commonly called a glycol. 

The crucial step is a back-side attack by the solvent on theprotonated epoxide. Step I Protonation of the epoxide activates it toward nucleophilic atiadc. 

Step 2 Back-side attack by the solvent (water) opens the ring. 

EXAMPLE Acid-catalyzed hydrolysis of propylene oxide (epoxypropane). 

The body oxidizes the alkene components of drugs and other substances to epoxides, which are then hydroiyzed to diols by an epoxide hydrolase enzyme. The more reactive epoxides are rapidly converted to water-soluble diols and eliminated in the urine. Epoxide hydrolase enzymes are sometimes used in organic synthesis to produce chiral diols. 

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Mechanism 8-10 Acid-Catalyzed Opening of Epoxides 362 8-14 Syn Dihydroxylation of Alkenes 364 8-15 Oxidative Cleavage of Alkenes 366 8-16 Polymerization of Alkenes 369 8-17 Olefin Metathesis 373... 

Mechanism 14-2 Acid-Catalyzed Opening of Epoxides in Water 649... 

In proposing mechanisms for I acid-catalyzed opening of epoxides, I imagine that the protonated epoxide opens to the more stable (more substituted) carbocation. 

CHAPTER 8 Ionic Addition of HX to an Alkene 332 Free-Radical Addition of HBr to Alkenes 334 Acid-Catalyzed Hydration of an Alkene 338 Oxymercuration of an Alkene 340 Hydroboration of an Alkene 345 Addition of Halogens to Alkenes 350 Formation of Halohydrins 352 Epoxidation of Alkenes 360 Acid-Catalyzed Opening of Epoxides 362 Olefin Metathesis 376... 

Hydride Reduction of a Carbonyl Group 454 Reaction of a Tertiary Alcohol with HBr(S[ 1) 480 Reaction of a Primary Alcohol with HBr (SN2) 480 Reaction of Alcohols with PBr3 485 (Review) Acid-Catalyzed Dehydration of an Alcohol 487 The Pinacol Rearrangement 495 Cleavage of an Ether by HBr or HI 639 Acid-Catalyzed Opening of Epoxides in Water 649 Acid-Catalyzed Opening of an Epoxide in an Alcohol Solution 650... 

Once the epoxide has been formed, it can then be opened with water under either acid-catalyzed or base-catalyzed conditions. Both sets of conditions are explored and compared in more detail in Section 14.10. For now, we will explore only the acid-catalyzed opening of epoxides, as seen in Mechanism 9.6. Under these conditions, the epoxide is first protonated to produce an intermediate that is very similar to a bromonium or mercurinium ion. All three cases involve a three-membered ring bearing a positive charge ... 

Mechanism 14-3 Acid-Catalyzed Opening of an Epoxide in an Alcohol Solution 650... 

In Alcohols When the acid-catalyzed opening of an epoxide takes place with an alcohol as the solvent, a molecule of alcohol acts as the nucleophile. This reaction produces an alkoxy alcohol with anti stereochemistry. This is an excellent method for making compounds with ether and alcohol functional groups on adjacent carbon atoms. For example, the acid-catalyzed opening of 1,2-epoxycyclopentane in a methanol solution gives fran.v-2-methoxycyciopcntanol. 

The Opening of Squalene-2,3-Epoxide Steroids are tetracyclic compounds that serve a wide variety of biological functions, including hormones (sex hormones), emulsifiers (bile acids), and membrane components (cholesterol). The biosynthesis of steroids is believed to involve an acid-catalyzed opening of squalene-2,3-epoxide (Figure 14-6). Squalene is a member of the class of natural products called terpenes (see Section 25-8). The enzyme squalene epoxidase oxidizes squalene to the epoxide,... 

Cyclization of squalene epoxide begins with the acid-catalyzed opening of the epoxide. Each additional cyclization step forms another carbocation. 

Although cyclization of squalene-2,3-epoxide is controlled by an enzyme, its mechanism is similar to the acid-catalyzed opening of other epoxides. The epoxide oxygen becomes protonated and is attacked by a nucleophile. In this case, the nucleophile is a pi bond. The initial result is a tertiary carbocation (Figure 14-7). 

The reaction of an epoxide with hydroxide ion leads to the same product as the acid-catalyzed opening of the epoxide a 1,2-diol (glycol), with anti stereochemistry. In fact, either the acid-catalyzed or base-catalyzed reaction may be used to open an epoxide, but the acid-catalyzed reaction takes place under milder conditions. Unless there is an acid-sensitive functional group present, the acid-catalyzed hydrolysis is preferred. 

Diols can be prepared by direct hydroxylation of an alkene with OSO4 followed by reduction with NaHSOs (Section 7.8). The reaction takes place readily and occurs with syn stereochemistry. We ll see in the next chapter that 1,2-diols can also be prepared by acid-catalyzed hydrolysis of epoxides—compounds with a three-membered, oxygen-containing ring. Epoxide opening is complementary to direct hydroxylation because it occurs with anti stereochemistry. 

Acid-catalyzed opening of saturated hydroxy epoxides via intramolecular participation of the hydroxyl group leads to regio- and stereoselective formation of tetrahy-drofuran and tetrahydropyran systems. 

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