Terminal alkynes with alkyl halides

They react with alkyl halides to give internal alkynes (see Section 5.5.2) via nucleophilic substitution reactions. This type of reaction also is known as alkylation. Any terminal alkyne can be converted to acetylide and alkynide, and then alkylated by the reaction with alkyl halide to produce an internal alkyne. In these reactions, the triple bonds are available for electrophilic additions to a number of other functional groups. 

We have already encountered one type of organometallic compound with a negative charge on carbon sodium acetylides, covered in Section 9-7. Terminal alkynes are weakly acidic, and they are converted to sodium acetylides by treatment with an unusually strong base, sodium amide. These sodium acetylides are useful nucleophiles, reacting with alkyl halides and carbonyl compounds to form new carbon-carbon bonds. 

Synthesis of secootkiry eokois from l-aOtynes. Dihydroboration at room temperature of a terminal alkyne with either (I) or 9-BBN gives a 1,1-diborylalkane (3) this is treated at 0-5° with I eq. of methyllithium in ether. The product (4) rearranges to (S). An alkyl halide (100 excess) is then added, and the resultant secondary organo-borane (6) is oxidized with alkaline hydrogen peroxide. Secondary alcohols (7) are obtained in 70-85% yield. 

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. 

Brown et al [8] have devised a general, convenient, and simple synthesis of straight-chain alcohols from internal alkynes. Long-chain internal alkynes, prepared by Eiters procedure [9] by metalating 1-alkynes, followed by treatment with alkyl halides, are isomerized to 1-alkynes on treatment with potassium-3-aminopropylamide (KAPA) [10] in 1,3-diaminopropane (APA). KAPA is prepared by the quantitative reaction of potassium hydride with excess of (APA) [10]. This difunctional superbase produces exceptionally rapid migration of internal C=C to the terminal C=C position. The terminal alkynes thus obtained are subjected to dihydroboration with 2 equiv of 9-BBN. The dibora intermediate on alkaline hydrogen peroxide oxidation provides 61-80% yield (Table 6.4) [8] of the corresponding alcohols (Eq. 6.2). 

Reaction of an acetylide ion (formed by removing a proton from a terminal alkyne) with an alkyl halide (7.11). 

While testing two different catalysts, Tanaka found that cationic rhodium in a binary system (cationic Rh(I)/H8-binap) is effective in chemo- and regioselective addition reactions of terminal alkynes with acetylenedicarboxylate to form 1,2,3,4-tetra-substituted benzenes with excellent yield of 99% [9, 44, 45]. It is also important to note that this reaction is tolerant to a large number of functional groups, including alkenes, alkyl halides, and esters. Although cationic iridium complex Ir(I) did not give a positive result in the cycloaddition reactions, the authors showed that the catalytic system with neutral Ir(I) can facilitate cycloaromatization of dimethyl acetylenedicarboxylate and terminal alkynes [45]. 

In Grignard reactions, Mg(0) metal reacts with organic halides of. sp carbons (alkyl halides) more easily than halides of sp carbons (aryl and alkenyl halides). On the other hand. Pd(0) complexes react more easily with halides of carbons. In other words, alkenyl and aryl halides undergo facile oxidative additions to Pd(0) to form complexes 1 which have a Pd—C tr-bond as an initial step. Then mainly two transformations of these intermediate complexes are possible insertion and transmetallation. Unsaturated compounds such as alkenes. conjugated dienes, alkynes, and CO insert into the Pd—C bond. The final step of the reactions is reductive elimination or elimination of /J-hydro-gen. At the same time, the Pd(0) catalytic species is regenerated to start a new catalytic cycle. The transmetallation takes place with organometallic compounds of Li, Mg, Zn, B, Al, Sn, Si, Hg, etc., and the reaction terminates by reductive elimination. 

Anions of acetylene and terminal alkynes are nucleophilic and react with methyl and primary alkyl halides to form carbon-carbon bonds by nucleophilic substitution Some useful applications of this reaction will be discussed m the following section... 

Alkyne alkylation is not limited to acetylene itself. Any terminal alkyne can be converted into its corresponding anion and then alkylated by treatment with an alkyl halide, yielding an internal alkyne. For example, conversion of 1-hexyne into its anion, followed by reaction with 1-bromobutane, yields 5-decyne. 

Propargyl dianion (QF I ). This anion can be prepared by dilithiation of allene with BuLi in 1 1 ether/hexane. Use of THF (- 50°) or BuLi/TMEDA results in a mixture of propargylide and allenyl anions. The anion couples readily with alkyl and allyl halides to give terminal alkynes. The intermediate lithium acetylide can also react with various electrophiles.3 Example ... 

Silver nitrate test The compound to be tested is treated with a few drops of 1% alcoholic silver nitrate. A white precipitate indicates a positive reaction. This could be due to either silver chloride (reaction with a reactive alkyl halide), silver alkynide (reaction with a terminal alkyne), or the silver salt of a carboxylic acid (reaction with a carboxylic acid). 

Longer-chain alkyl halides may not be commercially available, but they are readily made in one step from the corresponding alcohols (Larock, 1999), as are tosylates and mesylates. Similarly, longer-chain terminal alkynes are not commercially available, but can be readily made by reaction of alkyl halides with lithium acetylide-ethylene diamine complex in dry... 

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