Alkynes deprotonation with strong base

Alkynes also undergo a reaction that has no analogy in alkene chemistry. Because a C - H bond of an alkyne is more acidic than a C - H bond in an alkene or an alkane, alkynes are readily deprotonated with strong base. The resulting nucleophiles react with electrophiles to form new carbon-carbon o bonds, so that complex molecules can be prepared from simple starting materials. The study of alkynes thus affords an opportunity to learn more about organic synthesis. 

Alkynes can also be prepared from other alkynes. The reaction of terminal alkynyl anions with alkylating agents, snch as primary haloalkanes, oxacyclopropanes, aldehydes, or ketones, results in carbon-carbon bond formation. As we know (Section 13-2), such anions are readily prepared from terminal alkynes by deprotonation with strong bases (mostly alkyllithium reagents, sodinm amide in liqnid ammonia, or (jrignard reagents). Alkylation... 

In the remainder of this chapter, particular reactions are selected for examination of their synthetic potential. Acetylide ions are useful for linking carhon chains, particularly where a double bond is desired with stereoselectivity. Acetylene and 1-alkynes may be deprotonated with strong bases such as LDA and then treated with alkyl halides or carbonyl compounds. Preformed lithium acetylide complexed with ethylenediamine is available as a dry powder. Several alkynes derived from acetylide and carbon dioxide or formaldehyde are available, including propargyl alcohol (HC CCHjOH), propargyl bromide (HC CCH Br), and methyl propio-late (HC=CC02CH3). 

Higher alkynes can be synthesized fhom acetylene by reacting with NaNH followed by treatment with the appropriate alkyl halide.Terminal alkynes can be deprotonated using strong bases such as sodium amide. Hydroxides or alkoxides are not strong enough to deprotonate an acetylenic hydrogen. 

LDA is a strong base. Two E2 eliminations give an alkyne, which is deprotonated by the excess LDA to give an alkynyl anion. This species then reacts with Mel by an Sjsj-2 process. 

Corey s synthesis of leukotrienes, human metabolites that control many important natural defence reactions like inflammation, involves the lithium derivative of an alkyne prepared by deprotonation with the very strong base butyllithium. The tosyl derivative of a primary alcohol reacts with this lithium derivative and a perfectly normal S>j-2 reaction follows. The alkyne provides the carban-ion (Chapter 8) for the displacement of the tosylate. 

The converse of this idea is central to a useful bit of chemoselectivity that can be obtained in the reactions of dianions. 1-Propynol can be deprotonated twice by strong bases—first, at the hydroxyl group to make an alkoxide anion (the pIQ of the OH group is about 16) and, secondly, at the alkyne (pKa of the order of 25) to make a reacts with electrophiles it always reacts at the alkynyl anion and not at the alkoxide. 

KHMDS is a strong enough base to deprotonate terminal alkynes. It has been particularly useful for the intramolecular condensation of alkyne anions with aldehydes. For instance, the final cycliza-tion in the synthesis of a new bicyclic tetrahydropyridine system was carried out in the presence of KHMDS (eq 40). The same reaction failed when using LDA in THE... 

In the synthesis of propargylic alcohols, we saw the reaction of an alkynyl nucleophile (either the anion RC=CNa or the Grignard RC CMgBr, both prepared from the alkyne RC CH) with a carbonyl electrophile to give an alcohol product. Such acetylide-type nucleophiles will undergo Sn2 reactions with alkyl halides to give more substituted alkyne products. With this two-step sequence (deprotonation followed by alkylation), acetylene can be converted to a terminal alkyne, and a terminal alkyne can be converted to an internal alkyne. Because acetylide anions are strong bases, the alkyl halide used must be methyl or 1° otherwise, the E2 elimination is favored over the Sn2 substitution mechanism. 

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