Nucleophiles acetylide anions

The nucleophilic acetylide anion uses its electron lone pair to form a bond to the positively polarized, electrophilic carbon atom of bromomethane. As the new C-C bond begins to form, the C-Br bond begins to break in the transition state. 

Because an alkyl group is added to the original alkyne molecule, this type of reaction is called an alkylation reaction. We limit our discussion in this chapter to reactions of acetylide anions with methyl and primary haloalkanes. We will discuss the scope and limitation of this type of nucleophilic substitution in more detail in Chapter 7. For reasons we will discuss there, alkylation of nucleophilic acetylide anions is practical only for methyl and primary halides. While this alkylation reaction can be used with limited success with secondary haloalkanes, it fails altogether for tertiary haloalkanes. 

The only common synthons for alkynes are acetylide anions, which react as good nucleophiles with alkyl bromides (D.E. Ames, 1968) or carbonyl compounds (p. 52, 62f.). 

These compounds are sources of the nucleophilic anion RC=C and their reaction with primary alkyl halides provides an effective synthesis of alkynes (Section 9 6) The nucleophilicity of acetylide anions is also evident m their reactions with aldehydes and ketones which are entirely analogous to those of Grignard and organolithium reagents... 

The presence of a negative charge and an unshared electron pair on carbon makes acetylide anions strongly nucleophilic. As a result, they react with many different kinds of electrophiles. 

A wide array of substances can be prepared using nucleophilic substitution reactions. In fact, we ve already seen examples in previous chapters. The reaction of an acetylide anion with an alkyl halide (Section 8.8), for instance, is an Sn2 reaction in which the acetylide nucleophile replaces halide. 

Retrosynthetic cleavage of the indicated bond in 9 provides acetylenic aldehyde 23 as a potential precursor. It was anticipated that the action of a suitable base on 23 would result in the formation of an acetylide anion, a competent carbon nucleophile that could... 

Potassium or lithium derivatives of ethyl acetate, dimethyl acetamide, acetonitrile, acetophenone, pinacolone and (trimethylsilyl)acetylene are known to undergo conjugate addition to 3-(t-butyldimethylsiloxy)-1 -cyclohexenyl t-butyl sulfone 328. The resulting a-sulfonyl carbanions 329 can be trapped stereospecifically by electrophiles such as water and methyl iodide417. When the nucleophile was an sp3-hybridized primary anion (Nu = CH2Y), the resulting product was mainly 330, while in the reaction with (trimethylsilyl)acetylide anion the main product was 331. 

Here too, a second alkylation can be made to take place yielding RC=CR or R C=CR. It should, however, be remembered that the above carbanions—particularly the acetylide anion (57)—are the anions of very weak acids, and are thus themselves strong bases, as well as powerful nucleophiles. They can thus induce elimination (p. 260) as well as displacement, and reaction with tertiary halides is often found to result in alkene formation to the exclusion of alkylation. 

Acetylenes with a hydrogen atom attached to the triple bond are weakly acidic (pATa about 25) due to the stability of the acetylide anion (see Section 4.3.4), and this anion can then act as a nucleophile. 

Zhu and coworkers have applied another Ga-based system to the desymmetriza-tion of meso epoxides using acetylide anions as nucleophiles. A complex generated from Mc3Ga and a novel salen provides modest selectivities and yields using phenylacetyhde as the nucleophile ... 

A second group of important carbon nucleophiles are the acetylide anions. These nucleophiles are generated by treating 1-alkynes with a very strong base, such as amide ion ... 

Remember to work backward. The target ketone has five carbons, whereas the designated starting material has only three, so it is necessary to form a carbon-carbon bond. A nucleophilic substitution reaction can be done at C-l of 1-chloropropane. so a two-carbon nucleophile that can be ultimately converted to a ketone is required. A carbon-carbon bond-forming reaction that meets these requirements is the alkylation of an acetylide anion (see Section 10.8). Once the carbon-carbon bond has been formed, hydration of the alkyne can be used to convert the triple bond to a ketone ... 

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. 

First we note that it is necessary to form a carbon-carbon bond because the starting material has only two carbons and the target has seven. Because the starting material is an alkyne, we can probably use an acetylide anion as the nucleophile to form the carbon-carbon bond (see Section 10.8). How can a ketone functional group be introduced Section 11.6 described the hydration of an alkyne to produce a ketone. Our retrosynthetic analysis then becomes ... 

Carbon nucleophiles are very useful species because their reactions with carbon electrophiles result in the formation of carbon—carbon bonds. Section 10.8 introduced acetylide anions as nucleophiles that could be used in Sm2 reactions. These nucleophiles are prepared by reacting 1-alkynes with a strong base such as sodium amide. The relatively acidic hydrogen on the. vp-hybridized carbon is removed in this acid-base reaction ... 

Terminal alkynes are weakly acidic. The alkyne hydrogen can he removed by s strong base 9uch ae Na NH.. to yield nn a<%tylide anipn An acetylide anion ads as a nucleophile and can displace a halide ion from a primary alkyl halide in a n alkylation reaction. Acetylide anions are more stable iJian either alkyl anions or vinylic anions because their m ative charge is in a hybrid orbital with 50% s character, allowing the charge to be doser to the nucleus. 

Why is this reaction useful The acetylide anions formed by deprotonating terminal alkynes are strong nucleophiles that can react with a variety of electrophiles, as shown in Section 11.11. 

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. 

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