Nucleophiles acetylides

We won t study the details of this substitution reaction until Chapter 11 but for now can picture it as happening by the pathway shown in Figure 8.6. The nucleophilic acetylide ion uses an electron pair to form a bond to the positively polarized, electrophilic carbon atom of bromomethane. As the new C-C bond forms, Br- departs, taking with it the electron pair from the former C-Br bond and yielding propyne as product. We call such a reaction an alkylation because a new alkyl group has become attached to the starting alkyne. 

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. 

Explain why alkynes are more acidic than alkanes and alkenes. Show how to generate nucleophilic acetylide ions and use them in syntheses. 

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. 

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. 

Reaction of Trimethylsilylacetylene/Acetylide with Electrophiles. Deprotonation of TMSA with n-BuLi or Grignard reagents produces nucleophilic acetylides, which can react with various electrophilic carbon centers such as carbonyls, alkyl halides, or epoxides. 

There have been significant discoveries of methods that enable the enantioselective addition of an alkyne to an aldehyde or a ketone [182]. The resulting chiral propargyl alcohols are amenable to a wide variety of subsequent structural modifications and function as useful, versatile chemical building blocks. In 1994, Corey reported the enantioselective addition reactions of boryl acetylides such as 292, prepared from the corresponding stannyl acetylenes (e.g., 291) in the presence of the oxazaborolidine 293 as the chiral catalyst (Scheme 2.36) [183]. Both aliphatic and aromatic aldehydes were demonstrated to participate in these addition reactions, which proceeded in high yields and with impressive enantioselectivity. The proposed transition state model 295 is believed to involve dual activation both of the nucleophile (acetylide) and of the electrophile (aldehyde). The model bears a resemblance to the constructs previously proposed for alkylzinc addition reactions (Noyori, 153) and borane reductions (Corey. 188). 

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