Nucleophilic Ring-opening

Epoxides provide another useful a -synthon. Nucleophilic ring opening with dianions of carboxylic acids (P.L. Creger, 1972) leads to y-hydroxy carboxylic acids or y-lactones. Addition of imidoester anions to epoxides yields y-hydroxyaldehyde derivatives after reduction (H.W. Adickes, 1969). 

We saw an example of nucleophilic ring opening of epoxides in Section 15 4 where the reaction of Grignard reagents with ethylene oxide was described as a synthetic route to primary alcohols... 

Nucleophilic ring opening of epoxides has many of the features of an 8 2 reac tion Inversion of configuration is observed at the carbon at which substitution occurs... 

As we ve just seen nucleophilic ring opening of ethylene oxide yields 2 substituted derivatives of ethanol Those reactions involved nucleophilic attack on the carbon of the ring under neutral or basic conditions Other nucleophilic ring openings of epoxides like wise give 2 substituted derivatives of ethanol but either involve an acid as a reactant or occur under conditions of acid catalysis... 

FIGURE 16 6 The mecha nism for the acid catalyzed nucleophilic ring opening of ethylene oxide by water... 

The reactivity of epoxides toward nucleophilic ring opening is responsible for one of the biological roles they play Squalene 2 3 epoxide for example is the biological... 

Nucleophilic ring opening of epoxides by ammonia (Section 16 12) The strained ring of an epoxide is opened on nucleo philic attack by ammonia and amines to give 3 ammo alcohols Azide ion also re acts with epoxides the products are p azido alcohols... 

The direction of nucleophilic ring opening of unsymmetrical perfluoroepoxides has been shown to be a function of the nature of the nucleophile and the solvent (23,28). Although many oligomeric products have been prepared by this procedure and variations of it, no truly high polymers have been obtained... 

Nucleophilic Ring Opening. Opening of the ethyleneimine ring with acid catalysis can generally be accompHshed by the formation of an iatermediate ayiridinium salt, with subsequent nucleophilic substitution on the carbon atom which loses the amino group. In the foUowiag, R represents a Lewis acid, usually A = the nucleophile. 

Although reasonably stable at room temperature under neutral conditions, tri- and tetrametaphosphate ions readily hydrolyze in strongly acidic or basic solution via polyphosphate intermediates. The hydrolysis is first-order under constant pH. Small cycHc phosphates, in particular trimetaphosphate, undergo hydrolysis via nucleophilic attack by hydroxide ion to yield tripolyphosphate. The ring strain also makes these stmctures susceptible to nucleophilic ring opening by other nucleophiles. 

Dimethyl-1,2-dithiolylium perchlorate (488) when treated with ammonia at -5 °C underwent nucleophilic ring opening to (489). Subsequent ring closure with loss of H2S gave 4,5-dimethylisothiazole (490) in 85% yield (see Chapter 4.17). This reaction involved an initial attack of the ammonia at the unsubstituted 3-position. A small amount of the 3,4-dimethylisothiazole (491 15%) indicated that some attack of the ammonia also occurred at the 5-position. 

The reaction of oxiranes with base can follow several paths, giving products of type (34-38 Scheme 27). (a) Formation of an oxiranyl anion (34) is rare (Section 5.05.3.5). (b) Nucleophilic ring opening to give (35) is common with unhindered bases (Section 5.05.3.4). (c) a-Elimination to give a carbene or carbenoid (36) is favored by alkyllithium bases and... 

Benzisoxazolium salts, N-ethyl-nucleophilic ring opening, 6, 32... 

If the addition of Br to the alkene results in a bromonium ion, the anti stereochemistry can be readily eiqilained. Nucleophilic ring opening by bromide ion would occur by backside attack at carbon, with rupture of one of the C—Br bonds, giving overall anti addition. 

The 2,3-epoxy alcohols are often obtained in high optical purity (90% enantiomeric excess or higher), and are useful intermediates for further transformations. For example by nucleophilic ring opening the epoxide unit may be converted into an alcohol, a /3-hydroxy ether or a vicinal diol. 

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