Reactions of Alkyne Anions

As noted above, alkyne anions are very useful in Sn2 reactions with alkyl halides, and in acyl addition reactions to a carbonyl.46 Alkyl halides and sulfonate esters (tosylates and mesylates primarily) serve as electrophilic substrates for acetylides. A simple example is taken from Kaiser s synthesis of niphatoxin B, in which propargyl alcohol (36) is treated with butyllithium and then the OTHP derivative of 8-bromo-1-octanol to give a 47% yield of 37.48 

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 

The other major synthetic use of alkyne anions is their reaction with ketones and aldehydes to give an alkynyl alcohol via nucleophilic acyl addition. The lithium salt of 1-propyne, for example, reacted with aldehyde 40 to give alcohol 41 as part of Smith s synthesis of (+)-acutiphycin.50 The reaction is selective for ketones and aldehydes in the presence of acid derivatives, if the acetylide is not present in large excess. l 

The reaction is not limited to simple alkynes, of course. Terminal alkynes in general give the reaction and a variety of polar substituents can be incorporated.52 Acetylides show some propensity for 1,2-addition in conjugated systems, especially if the p-carbon of the double bond is hindered. 

Chapter 8. Nucleophilic Species That Form Carbon-Carbon Bonds 

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An alkyne anion is a carbanion, and it is relatively strong base. A t3rpi-cal acid-base reaction is the reaction of alkyne anion 15 (the sodium anion of ethyne) with ethanol to give a conjugate base (ethoxide, 16) and a conjugate acid... 

The most convenient pathway to this important class of compounds is the reaction of alkynes RG=GH with salts of the bis(acetylacetonato)gold anion.71 This reaction leads to almost any type of target compounds, including those with R = H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, etc. (Q = metal or quaternary or PPN cation Equation (22)). 

CuBr/QUINAP System The CuBr/QUlNAP system was initially used in the enan-tioselective synthesis of proparyl amines via the reaction of alkynes and enamines (Scheme 5.5). It was rationalized that the enamines reacted with protons in terminal alkynes in the presence of copper catalyst to form zwitterionic intermediates in which both the generated iminiums and alkyne anions coordinate to the copper metal center. After an intermolecular transfer of the alkyne moiety to the iminium ion, the desired products were released and the catalyst was regenerated. The combination of CuBr as catalyst and the chiral ligand QUEMAP is crucial for the good reactivities and enantioselectivities seen in the reaction. Another potential... 

Reactions with Protic, ionic, Poiar Reagents. The reactions of radical anions with proton donors include the reduction of arenes, the well-known Birch reduction, as well as alkynes by alkali metals in liquid ammonia. Both reactions have synthetic utility and belong to the few radical ion reactions included in elementary textbooks. 

The A1 atom is thought to coordinate with the oxygen of the epoxide in the first step of these reactions. The alkyne anion then reacts intramolecularly giving the product. 

Alkynes from aldehydes or ketones. The reaction of the anion ef 1 with diaryl ketones, ArCOAr, to form alkynes, ArC=CAr, was reported first by Colvin and Hamill, but the method was said to fail or give low yield with substrates with enolizable hydrogens. Since then experimental details have been perfected, and the method has proved to be useful." The anion of 1 is prepared with potassium f-butoxide, and the reaction with the carbonyl compound is conducted for 12-16 hours at —78° before it is allowed to warm to the ambient temperature. Linder these conditions, alkynes can be obtained in 50-80% yield from aldehydes, diaryl ketones, and alkyl aryl ketones, but not from dialkyl ketones. The proposed mechanism is shown in equation (I). 

Alkynic intermediates serve as important functional groups in organic synthesis. Many important reactions exploiting the unique and versatile chemistry of the carbon-carbon triple bond have been devised over the last few years. A general strategy for the synthesis of substituted alkynes involves substitution and addition reactions of propargylic anion equivalents this approach is particularly well suited for the preparation of homopropargylic alcohols (Scheme 28). 

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... 

Finally some homoleptic alkyne complexes of scandium and some rare earths are known. Tris(phenylethynyl) scandium is formed as a dark brown product after treatment of phenylethyne with butyl lithium at — 78°C in hexane, followed by the addition of scandium trichloride at room temperature. The compound is inflammable in air (Hart and Saran, 1968 Hart et al., 1970). The reaction of the anionic... 

The reaction of alkynes with HCl in acetic acid solution does take place by a heterolytic pathway. By analogy to the addition of electrophiles to alkenes, one might write a mechanism involving a vinyl cation, which could then combine with the nucleophile anion to produce the adduct (equation 9.65). Vinyl cations are much less stable than are 2° or 3° alkyl cations and allyl or benzyl cations, however. ... 

In this section, we cover one of two very important reactions of alkynes for organic synthesis. As we have seen (Section 4.4) an acetylide anion is a strong base. It is also a nucleophile—it has an unshared pair of electrons that it can donate to an electrophilic carbon atom to form a new carbon-carbon bond. 

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. 

Another carbon compound has an acidic proton, and the acid-base reaction is quite common. Alkynes (Chapter 5, Section 5.2) are categorized as internal alkynes (R-C=C-R) or terminal alkynes (R-C=C-H). The hydrogen atom of a terminal alkyne is a weak acid (pK of about 25), and strong bases such as sodium amide (NaNH2) remove that proton to give an alkyne anion (R-C=C ). In this reaction, the alkyne anion is the conjugate base of the alkyne, which is a weak acid. Alkyne anions are useful nucleophiles in many reactions (see Section 6.7). 

A new synthesis of aldehydes with 2-methyl-2-thiazoline has the advantage of releasing the aldehydes from the thiazolidine intermediate under neutral conditions . Acetylene derivatives can be obtained from aldehydes via dibromomethylene compounds Novel reactions of alkynes with cationoid electrophiles have been published. -Diketones and 2-ketoalkoximes can be obtained by this reaction from acid chlorides and aliphatic nitro compounds respectively Addition of aldehydes to activated carbon-carbon double bonds occurs smoothly in the presence of cyanide ions as catalysts . Poly- -carbonyl compounds have been prepared by condensation of two anions, whereby the enolate salt of a y8-keto ester condenses as an electrophilic anion with strong nucleophiles such as the dianion of benzoylacetone. ... 

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