Base-Catalyzed Ring Opening of Epoxides

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. 

Strong bases and nucleophiles do not attack and cleave most ethers. Epoxides are more reactive, however, because opening the epoxide relieves the strain of the three-membered ring. Strong bases can attack and open epoxides, even though the leaving group is an alkoxide. 

Step 1 A strong base attacks and opens the ring to an alkoxide. 

Like hydroxide, alkoxide ions react with epoxides to form ring-opened products. For example, cyclopentene oxide reacts with sodium methoxide in methanol to give the same /ra 25-2-methoxycyclopentanol produced in the acid-catalyzed opening in methanol. 

Amines can also open epoxides. Ethylene oxide reacts with aqueous ammonia to give the important industrial reagent ethanolamine. The nitrogen atom in ethanolamine is still nucleophilic, and ethanolamine can react further to give diethanolamine and triethanolamine. Good yields of ethanolamine are achieved by using 

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Base-Catalyzed. Ring Opening of Epoxides. Base-catalyzed ring opening of epoxides provides a route to allylic alcohols.150... 

Base-catalyzed ring opening of epoxides constitutes a route to allylic alcohols. 

Scheme 9.8 (depicts some base-catalyzed ring-openings of epoxides. 

In a base-catalyzed ring opening of an epoxide, the nucleophilic attack is on the less substituted (less hindered) carbon atom in the epoxide ring. The mechanism is shown below. 

A MECHANISM FOR THE REACTION ] Acid-Cataiyzed Ring Opening of an Epoxide 525 [ A MECHANISM FOR THE REACTION ] Base-Catalyzed Ring Opening of an Epoxide 526... 

Acid-Catalyzed Ring Opening of an Epoxide 525 Base-Catalyzed Ring Opening of an Epoxide 526... 

The first example of asymmetric catalytic ring-opening of epoxides with sp2-hybridized carbon-centered nucleophiles was reported by Oguni, who demonstrated that phenyllithium and a chiral Schiff base ligand undergo reaction to form a stable system that can be used to catalyze the enantioselective addition of phenyllithium to meso-epoxides (Scheme 7.24) [48]. Oguni proposed that phenyllithium... 

Next to the above presented use of SiCl for the in situ preparation of a Lewis acid catalyst with a Lewis base for the aldol reaction, it is possible to apply this compound as a reagent in the ring opening of epoxides leading to chlorinated alcohols. Denmark [104] reported that the chiral phosphoramide 38 catalyzed the asymmetric ring opening reaction of meso-epoxides in the presence of tetrachlo-rosilane. Similar examples were provided by Hashimoto in 2002 [105], applying the A -oxide 39 as catalyst (Scheme 30). 

A tridentate Schiff base Cr(III) complex derived from l-amino-2-indanol catalyzes the enantioselective ring opening of meso A-2,4-dinitrobenzyl aziridines with TMSN3 (Sch. 18) [96]. The chiral (salen)metal complexes, used in the enantioselective ring opening of epoxides, were found to be much less effective (for Cr) or inactive (for Co). 

Ring openings of epoxides with various nucleophiles are catalyzed by acid or base and are accompanied by configurational inversion on the substituted carbon (23). Posner found that y-alumina facilitated nucleophilic ring openings of epoxides with amines, alcohols, and carboxylates to give P-functionalized alcohols stereospecihcally (trans) in good yields under mild reaction conditions (24). This catalytic behavior of alumina was assumed to be due to the cooperative function of acidic and basic sites on alumina. 

Epoxides can also undergo base-catalyzed ring opening. Such reactions do not occur with other ethers, but they are possible with epoxides (because of ring strain), provided that the attacking nucleophile is also a strong base such as an alkoxide ion or hydroxide ion. 

A few examples of base promoted domino ring opening lactonization of epoxides with active methylene compounds (malonate, cyanoacetate, acetoacetates) are known earlier in the literature [42]. Pizzo s group has recently described domino nucleophilic ring opening of epoxides by active methylenes, catalyzed by polymer-supported bases, under solvent-free conditions (SolFCs) (Scheme 4.24)... 

This chapter will focus on nucleophilic additions to unsaturated bonds catalyzed by bases or acids, excluding the use of organometallic species, which is discussed in Chapter 4, and on nucleophilic substitutions including ring opening of epoxides and allylic substitutions. 

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