Base-Catalyzed Opening of Epoxides

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 

Propose a complete mechanism for the reaction of cyclopentene oxide with sodium methoxide in methanol. 

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Mechanism 14-4 Base-Catalyzed Opening of Epoxides 653 14-14 Orientation of Epoxide Ring Opening 654 14-15 Reactions of Epoxides with Grignard and Organolithium Reagents 656 14-16 Epoxy Resins The Advent of Modern Glues 656 Summary Reactions of Epoxides 658 EssentialTerms 660 Study Problems 662... 

Scheme 2 Generalization of Lewis base-catalyzed opening of epoxides with SiCLt...

Many other reports of ligand libraries for specific catalytic applications have been reported. Among them, Gilbertson and co-workers reported a chiral phosphine library, tested in the rhodium-catalyzed asymmetric hydrogenation of an enamide (158,159), and a similar library for the palladium-catalyzed allylation of malonates (160, 161) Hoveyda and co-workers (162, 163) reported a chiral Schiff base library, screened in the titanium-catalyzed opening of epoxides with (TMSCN) (trimethyl silyl cyanide) ... 

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 ... 

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... 

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

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). 

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

In recent years there has been considerable progress both in the base-catalyzed isomerization of meso-epoxides and in the metal-free catalysis of enantioselective opening of meso epoxides. The former approach has proven its potential in sev-... 

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. 

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. 

There is a frequently noted incompatibility of organoiithiums with many chiral Lewis acids, which are often employed for asymmetric openings of epoxides [99]. Analogous Lewis base-catalyzed reactions are rare [100]. However, activation by Lewis acids, such as BFj OEt2, is necessary for the opening of less reactive epoxides [101]. While organoiithiums are rarely employed, applications of hetero-nucleophiles are well known in enantioselective desymmetrizations of meso-epoxides [102]. 

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

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