Nucleophilic addition acetylide ions

Conjugate addition is most often observed when the nucleophile (Y ) is weakly basic The nucleophiles m the two examples that follow are C=N and C6H5CH2S respectively Both are much weaker bases than acetylide ion which was the nucleophile used m the example illustrating direct addition... 

Ab initio calculations at the HF/6-31G level have been used to explore energy changes, structural variation, and electron density shifts during jr-face selective addition of substituted acetylide ions to cyclohexanone and cyclohexanethione. Charge polarization of the jr-bond on approach of the nucleophile is such that the carbonyl carbon becomes considerably electron deficient for most of the reaction path (and may... 

Two different approaches are commonly used for the synthesis of alkynes. In the first, an appropriate electrophile undergoes nucleophilic attack by an acetylide ion. The electrophile may be an unhindered primary alkyl halide (undergoes Sn2), or it may be a carbonyl compound (undergoes addition to give an alcohol). Either reaction joins two fragments and gives a product with a lengthened carbon skeleton. This approach is used in many laboratory syntheses of alkynes. 

An acetylide ion can serve as the nucleophile in this addition to a carbonyl group. The acetylide ion adds to the carbonyl group to form an alkoxide ion. Addition of dilute acid (in a separate step) protonates the alkoxide to give the alcohol. 

Acetylide ion alkylation is limited to primary alkyl bromides and iodides, RCHgX, for reasons that will be discussed in detail in Chapter 11. In addition to their reactivity as nucleophiles, acetylide ions are sufficiently strong bases that they cause dehydrohalogenation instead of substitution when they react with secondary and tertiary alkyl halides. For example, reaction of bromocyclohexane with propyne anion yields the elimination product cyclohexene rather than the substitution product cyclohexylpropyne. 

The great majority of known2 reactions of acetylenes are with electrophiles either via the acetylide ions RC=C", or by way of electrophilic addition reactions to the triple bond. Nucleophilic acetylenic substitutions (Sat-A) are generally unfavorable2. Alkynyl(phenyl)iodonium species may serve as synthons for the electrophilic alkynyl... 

An acetylide ion is another example of a carbon nucleophile that reacts with an aldehyde or a ketone to form a nucleophilic addition product. When the reaction is over, a weak acid (one that will not react with the triple bond, such as the pyridinium ion shown here) is added to the reaction mixture to protonate the alkoxide ion. 

Li proposed that copper acetylide is generated and undergoes nucleophilic addition to the iminium ion, which is generated hy Cu-catalyzed oxidation of THIQ. 

Now, let s draw the forward scheme. Radical bromination of 2-methylbutane produces the tertiary alkyl hahde, selectively. Then, elimination with NaOEt, followed by awti-Markovnikov addition (HBr / peroxides), and then elimination with iert-butoxide, followed by another awri-Markovnikov addition (HBr / peroxides) produces l-bromo-3-methylbutane. This alkyl hahde will then undergo an Sn2 reaction when treated with an acetylide ion to give 5-methyl-1-hexyne. Ozonolysis of this terminal alkyne cleaves the CC triple bond, producing the carboxylic acid. Deprotonation (with NaOH) produces a carboxylate nucleophile that subsequently reacts with bromomethane in an Sn2 reaction to give the desired ester. 

Reactions that form carbon-carbon bonds are extremely important in synthesis because they enable larger compounds, containing more carbons, to be constructed from smaller compounds. This requires the reaction of a carbon nucleophile with a carbon electrophile. The most important carbon nucleophiles that we have encountered so far are cyanide ion and acetylide anions (see Section 10.8). If we remember that acetylide anions can be reduced to c/.v-alkenes (see Section 11.12), then all of the addition products of this chapter are accessible from simple alkynes. 

The processes must be oxidative for inclusion. Metals such as copper and iron can catalyze the addition of allgmes to amines in a CDC process that is presumed to involve an intermediate iminium ion and formation of metal acetylides as the reactive nucleophiles. The oxidative component of this reaction is the generation of the iminium ion. The corresponding non-oxidative process, the aldehyde-allg ne-amine (A ) coupling, will not be a focus here and has been recently reviewed. Interesting intramolecular processes such as cyclizations involving hydride transfers that are overall redox neutral must be similarly excluded. ... 

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