Epoxides with acetylide anions

The proton of terminal acetylenes is acidic (pKa= 25), thus they can be deprotonated to give acetylide anions which can undergo substitution reactions with alkyl halides, carbonyls, epoxides, etc. to give other acetylenes. 

Terminal alkynes are readily converted to acetylide anions with strong base. These anions are strong nucleophiles, capable of reacting with electrophiles such as alkyl halides and epoxides. 

A Sn2 reaction of an alkyl halide with an acetylide anion, C=CR 11.11B Opening of an epoxide ring with an acetylide anion, C=CR... 

Opening of an epoxide ring with an acetylide anion, X=CR... 

Trimethylsilylallenes behave as propargylic anion equivalents during the titanium tetrachloride catalysed addition to carbonyl compounds, leading to homopropargylic carbinols. This new approach should prove useful in the synthesis of branched acetylenes which are not accessible via alkylation of acetylide anions with alkyl halides and epoxides (Scheme 23). ... 

The fact that a strong base can be used to pull an H off an 5/7-hybridized carbon is another wrinkle that will be explored in upcoming activities. As a preview, note that the resulting acetylide anion is a carbon nucleophile that can be combined with carbon electrophiles to make a wide range of carbon-carbon bonds. The only example of this we have discussed so far is nucleophilic epoxide ring opening. 

Now, let s draw out the forward scheme. This multi-step synthesis uses three equivalents of ethylene (labeled A, B, C in the scheme below) and one equivalent of acetic acid (labeled D). Ethylene (A) is converted to 1,2-dibromoethane upon treatment with bromine. Subsequent reaction with excess sodium amide produces an acetylide anion which is then treated with bromoethane [made tfom ethylene (B) and HBr] to produce 1-butyne. Deprotonation with sodium amide, followed by reaction with an epoxide [prepared by epoxidation of ethylene (C)] and water workup, produces a compound with an alkyne group and an alcohol group. Reduction of the alkyne to the cis alkene is accomplished with H2 and Lindlar s catalyst, after which the alcohol is converted to a tosylate with tosyl chloride. Reaction with the conjugate base of acetic acid [produced by treating acetic acid (D) with NaOH] allows for an Sn2 reaction, thus yielding the desired product, Z-hexenyl acetate. 

As with cyanide, Sn2 reactions of alkyne anions can be done with substrates other than halides or sulfonate esters. Epoxides are opened by acetylides at the less sterically hindered carbon to give an alkynyl alcohol. A synthetic example is the reaction of epoxide 38 with the indicated lithium alkyne anion gave an 85% yield of 39, an intermediate in the Sinha et al. synthesis of squamotacin.49... 

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