Alkynes relative acidity

Standard organolithium reagents such as butyllithium, ec-butyllithium or tert-butyllithium deprotonate rapidly, if not instantaneously, the relatively acidic hydrocarbons of the 1,4-diene, diaryhnethane, triarylmethane, fluorene, indene and cyclopentadiene families and all terminal acetylenes (1-alkynes) as well. Butyllithium alone is ineffective toward toluene but its coordination complex with A/ ,A/ ,iV, iV-tetramethylethylenediamine does produce benzyllithium in high yield when heated to 80 To introduce metal into less reactive hydrocarbons one has either to rely on neighboring group-assistance or to employ so-called superbases. 

Silylation of acidic compounds.2 The combination of ethyl trimethylsilylacetate and 2-5 mole % of tetra-n-butylammonium fluoride (TBAF) is a markedly efficient reagent for transfer of trimethylsilyl groups to relatively acidic substrates such as ketones, alcohols, thiols, phenols, and carboxylic acids, and even 1-alkynes. KOCH3/ (18-crown-6) and Triton B are also effective catalysts. 

Conversion of a terminal alkyne to its alkynylsilane prevents loss of the relatively acidic terminal hydrogen (pKa of ethyne c. 25) during later synthetic steps. For example, the terminal hydrogen of propyne was masked whilst its propargylic anion was used in a synthesis of Cecropia juvenile hormone, a chemical which plays ail important role in insect development (Figure Si5.2). 

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 ... 

In the same vein, Schmalz has proposed a facile construction of the colchicine skeleton by a rhodium-catalyzed cyclization/cycloaddition cascade [56]. A TMS group has to be introduced on the alkyne moiety of 66 in order to avoid participation of the relatively acidic alkynyl hydrogen atom in undesired proton transfers. The resulting 6,7,7 of 67a and 67b architecture was assembled in a remarkably diastereoselective manner (14 1) and in satisfactory yield (Scheme 30). 

Organic compounds such as terminal alkynes (RC=CH) which contain relatively acidic hydrogen atoms form salts with the alkali metals, e.g. reactions 18.1, 18.2 and 13.30. 

Because the nonbonding orbital is occupied, stability increases with s character, the converse of the situation for carbocations. The order of stability of carbanions is sp < sp < sp. The relative stability of gas phase carbanions can be assessed by the energy of their reaction with a proton, which is called proton affinity. The proton affinities of the prototypical hydrocarbons methane, ethene, and ethyne have been calculated at the MP4/6-31+G level/ The order is consistent with the electronegativity trends discussed in Section 1.1.5, and the larger gap between sp and sp, as compared to sp and sp, is also evident. The relative acidity of the hydrogen in terminal alkynes is one of the most characteristic features of this group of compounds. 

The r-BuOK-catalyzed reaction of a terminal alkyne with cyclohexanone in DMSO to give a tertiary alcohol in 91% yield (eq 47) provides a straightforward illustration of an addition to a carbonyl compound. The same type of addition takes place in the nonpolar solvent benzene but the rate is slower and the yield lower. Treatment of cyclohexanone with ethynylbenzene under the same reaction conditions yields l-(phenylethynyl)cyclohexanol in 83% yield when the reaction is carried out using 1.0 equiv of r-BuOK in the absence of solvent the yield of the tertiary alcohol is 93%. Other aliphatic and aromatic ketones give similar results. Ketones with relatively acidic a hydrogens are capable of undergoing intermolecular aldol additions in the presence of the base but, apparently, the reversibility of this reaction allows the irreversible addition of the acetyUde anion to compete favorably. ... 

If we include in our comparison hydrogen compounds of other first-row elements of the periodic table, we can write the following orders of relative acidities and basicities. This comparison is useful as we consider what bases and solvents to use with terminal alkynes. 

Since sp-hybridized carbons are relatively acidic (pKa=25), strong bases can be used to deprotonate a terminal alkyne. If a Grignard reagent is used as the base, then the resulting product is drawn as a Grignard rather than an anion (this essentially sacrifices a more reactive, cheaper Grignard in the production of a new, more stable one— the desired alkynyl Grignard). 

The most striking difference in properties between alkenes and alkynes is that terminal alkynes (RC CH) are relatively acidic. When a terminal alkyne is treated with a strong base, such as sodium amide, Na" " NH2, the terminal hydrogen is removed and the corresponding acetylide anion is formed ... 

In Summary The characteristic hybridization scheme for the triple bond of an alkyne controls its physical and electronic features. It is responsible for strong bonds, the linear structure, and the relatively acidic alkynyl hydrogen. In addition, alkynes are highly energetic compounds, hitemal isomers are more stable than terminal ones, as shown by the relative heats of hydrogenation. 

As might be expected, the hybridization at nitrogen itself also drastically affects basicity, in the order jNHs > R2C=NR > RC=N , a phenomenon that we already enconntered in the discussion of the relative acidity of alkanes, alkenes, and alkynes (Section 13-2). Thus, iminium ions (Section 17-9) have valnes estimated to be of the order of 7 to 9 A-protonated nitriles (Section 20-8) are even more acidic (pa s < -5). Table 21-2 summarizes the pAa values of the conjugate acids of some representative amines. 

To probe the reaction mechanism of the silane-mediated reaction, EtjSiD was substituted for PMHS in the cyclization of 1,6-enyne 34a.5 The mono-deuterated reductive cyclization product 34b was obtained as a single diastereomer. This result is consistent with entry of palladium into the catalytic cycle as the hydride derived from its reaction with acetic acid. Alkyne hydrometallation provides intermediate A-7, which upon cw-carbopalladation gives rise to cyclic intermediate B-6. Delivery of deuterium to the palladium center provides C-2, which upon reductive elimination provides the mono-deuterated product 34b, along with palladium(O) to close the catalytic cycle. The relative stereochemistry of 34b was not determined but was inferred on the basis of the aforementioned mechanism (Scheme 24). 

Cleavage of Zr—C a bonds occurs readily on treatment with H20 or dilute acids, while the Zr—Cp bond usually survives mild protonolysis conditions. The use of D20 or DC1/D20 permits the replacement of Zr with D. Deuterolysis provides a generally reliable method for establishing the presence of Zr—C bonds. Protonolysis or deuterolysis of Zr—Csp bonds proceeds with retention of configuration [97]. In the hydrozirconation of terminal alkynes, deuterium can be introduced at any of the three positions in the vinyl group in a completely regio- and stereoselective manner, as shown in Scheme 1.18. Although relatively little is known about the mechanistic details, the experimental results appear to be consistent with concerted c-bond metathesis (Pattern 13) between C—Zr and H— X bonds. 

If an alkyne (or activated alkene) is present in the solution the sulfenic acid, from (57), or the alkanethiosulfoxylic acid (R SSOH), from (58), can be trapped, as shown in (59) and (60), respectively, and the course of the decomposition is relatively straightforward. [The thiocarbonyl compound formed in (57) normally forms polymer.]... 

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