Enolate Reactions with Non-Carbonyl Electrophiles

Enolates can react with many electrophilic species other than alkyl halides, analogous to the reactions of other carbanions (Chap. 8). Nucleophilic ring opening of an epoxide to give alcohols is very common, occurring at the less sterically hindered carbon. l Grieco et al. used the dilithio salt of acetic acid (LiCH2C02Li, 

The epoxide ring opening gives the interesting disconnection. 

It is also possible to oxygenate an enolate to give the corresponding acyloin (an a-hydroxy ketone) or alkoxy derivative. Reaction of an enolate anion with oxygen and trimethylphosphite [(MeO)3P], for example, gives an a-hydroxy derivative. 3 Reaction of an enol ether such as 105 with 3,3-dimethyldioxirane leads to the protected a-hydroxy ketone (106), in an example taken from Danishefsky s synthesis of myrocin An effective oxygenation reagent for enolate anions is MoOPh, and a typical use is taken from work by Vedejs to 

Enolates react with sulfenyl halides to give an a-alkylthio ketone. As shown for cyclohexanone, reaction with LDA followed benzenesulfenyl chloride (PhSCl) produced phenylthio derivative 109. The proton adjacent to both the carbonyl and the sulfur (the a-proton) was more acidic and it was deprotonated with potassium hydride, forming the enolate, and alkylation with iodobutane gave a 91% yield of 110. As mentioned in Chapter 2, the sulfide moiety can be oxidized to a sulfoxide and thermally eliminated (syn elimination, sec. 2.9.C.v) to give an alkene. 9 Similar methodology can be applied to selenides, R—Se—R. O 

In addition to the methods described for controlling the ratio of thermodynamic and kinetic products, other techniques have been developed to trap the enolate, based on reactions with reagents that prefer O-alkylation. Reaction of a ketone with acetic anhydride, usually in the presence of a catalytic amount of perchloric acid, generates the thermodynamic enol acetate When this is treated with methyllithium, the 

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