Acidic terminal alkynes

The alternative, reaction of a Grignard reagent with an alkynyl ketone, is not acceptable in this case. The acidic terminal alkyne C—H would transfer a proton to the Grignard reagent. 

Both KM11O4 and O3 oxidation of alkynes yield carboxylic acids terminal alkynes give CO2 also. In (a), (b), and (c), the observed products can also be formed by KMn04 oxidation of the corresponding alkenes. 

The oxidative coupling of terminal alkynes by copper salts, discovered in 1869 by Glaser, has evolved to the modified method reported in 1962 by Hay. In the Hay procedure, oxygen is passed through a solution of the alkyne and a catalytic amount of a copper(I) salt in a complex-forming solvent, such as pyridine and TMEDA. Although the oxidative coupling by Cu salt catalysts in suitable amines has wide scope, it is less successful for less acidic terminal alkynes, such as alkyl- or silyl-alkynes. 

The phase-transfer-assisted permanganate oxidation of alkynes and alkenes has been reviewed. Terminal and internal alkynes are oxidized to 1,2-dicarbonyl compounds by the combined action of diphenyl disulphide, ammonium peroxidisulphate and water or by sodium periodate in the presence of ruthenium dioxide (equation 34). Other reagents for the conversion of acetylenes into 1,2-dicarbonyl compounds are hydrogen peroxide in the presence of (2,6-dicarboxylatopyridine)iron(II), the complex oxo(A, A -ethylenebissalicylideneiminato)chromium(V) trifluoromethanesulphonate (216)and ruthenium tetroxide as a mediator in electrooxidation. l-Acetoxyalkan-2-ones 217 are obtained by the oxidation of terminal acetylenes with sodium perborate and mercury(II) acetate in acetic acid ". Terminal alkynes give a-ketoaldehydes 218 on treatment with dilute hydrogen peroxide, combined with mercury(II) acetate and sodium molybdate or sodium tungstate under phase-transfer conditions. ... 

Palladium-catalyzed trimerization of alkynes has been developed, " but simple terminal alkynes undergo dimerization to form enynes. A mechanism for the formation of head-o-tail enynes has been proposed that proceeds through palladium(iv) complexes 202 or 203. Probably, however, the acidic terminal alkyne will cleave the palladium-alkenyl bond to give the enyne product and an alkynylpalladium(ii) species that can enter a new catalytic cycle instead." ... 

Using the titanium Lewis acid, terminal alkynes and some internal alkynes can react with 1-aryl-l-alkylhydrazines to produce indole derivatives [315]. The indole derivatives may also be prepared via Fischer cyclization of the hydroamination... 

Terminal alkyne anions are popular reagents for the acyl anion synthons (RCHjCO"). If this nucleophile is added to aldehydes or ketones, the triple bond remains. This can be con verted to an alkynemercury(II) complex with mercuric salts and is hydrated with water or acids to form ketones (M.M.T. Khan, 1974). The more substituted carbon atom of the al-kynes is converted preferentially into a carbonyl group. Highly substituted a-hydroxyketones are available by this method (J.A. Katzenellenbogen, 1973). Acetylene itself can react with two molecules of an aldehyde or a ketone (V. jager, 1977). Hydration then leads to 1,4-dihydroxy-2-butanones. The 1,4-diols tend to condense to tetrahydrofuran derivatives in the presence of acids. 

There also exists an acidregioselective condensation of the aldol type, namely the Mannich reaction (B. Reichert, 1959 H. Hellmann, 1960 see also p. 291f.). The condensation of secondary amines with aldehydes yields Immonium salts, which react with ketones to give 3-amino ketones (=Mannich bases). Ketones with two enolizable CHj-groupings may form 1,5-diamino-3-pentanones, but monosubstitution products can always be obtained in high yield. Unsymmetrical ketones react preferentially at the most highly substituted carbon atom. Sterical hindrance can reverse this regioselectivity. Thermal elimination of amines leads to the a,)3-unsaturated ketone. Another efficient pathway to vinyl ketones starts with the addition of terminal alkynes to immonium salts. On mercury(ll) catalyzed hydration the product is converted to the Mannich base (H. Smith, 1964). 

Internal alkynes are oxidized to acytoins by thalliuin(III) in acidic solution (A. McKil-lop, 1973 G.W. Rotermund, 1975) or to 1,2-diketones by permanganate or by in situ generated ruthenium tetroxide (D.G. Lee, 1969, 1973 H. Gopal, 1971). Terminal alkynes undergo oxidative degradation to carboxylic acids with loss of the terminal carbon atom with these oxidants. 

Organoboranes undergo transmetallation. 1-Hexenylboronic acid (438) reacts with methyl acrylate via the transmetallation with Pd(OAc)2, giving methyl 2,4-nonadienoate (439)[399], The ( )-alkenylboranes 440, prepared by the hydroboration of terminal alkynes, are converted into the alkylated ( )-alkenes 441 by treatment with an equivalent amount of Pd(OAc)2 and triethylamine[400]. The ( )-octenylborane 442 reacts with CO in MeOH in the... 

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carboiiyiation. Two types of the oxidative carbonyla-tion of alkynes are known. The first is a synthesis of the alkynic carbox-ylates 524 by oxidative carbonylation of terminal alkynes using PdCN and CuCh in the presence of a base[469], Dropwise addition of alkynes is recommended as a preparative-scale procedure of this reation in order to minimize the oxidative dimerization of alkynes as a competitive reaction[470]. Also efficient carbonylation of terminal alkynes using PdCU, CuCI and LiCi under CO-O2 (1 I) was reported[471]. The reaction has been applied to the synthesis of the carbapenem intermediate 525[472], The steroidal acetylenic ester 526 formed by this reaction undergoes the hydroarylalion of the triple bond (see Chapter 4, Section 1) with aryl iodide and formic acid to give the lactone 527(473],... 

Many examples of insertions of internal alkynes are known. Internal alkynes react with aryl halides in the presence of formate to afford the trisubstituted alkenes[271,272]. In the reaction of the terminal alkyne 388 with two molecules of iodobenzene. the first step is the formation of the phenylacetylene 389. Then the internal alkyne bond, thus produced, inserts into the phenyl-Pd bond to give 390. Finally, hydrogenolysis with formic acid yields the trisubstituted alkene 391(273,274], This sequence of reactions is a good preparative method for trisubstituted alkenes from terminal alkynes. 

The alkynyl ketones 840 can be prepared by the reaction of acyi chlorides with terminal alkynes, Cul in the presence of Et3N is the cocatalyst[719]. (1-Alkynyl)tributylstannanes are also used for the alkynyl ketone synthesis[720]. The a,. 3-alkynic dithio and thiono esters 842 can be prepared by the reaction of the corresponding acid chloride 841 with terminal alkynes[721,722]. 

The 2,3-alkadienyl acetate 851 reacts with terminal alkynes to give the 2-alkynyl-1,3-diene derivative 852 without using Cul and a base. In the absence of other reactants, the terminal alkyne 853 is formed by an unusual elimination as an intermediate, which reacts further with 851 to give the dimer 854. Hydrogenolysis of 851 with formic acid affords the 2, 4-diene 855[524]. 

J-unsaturated ester is formed from a terminal alkyne by the reaction of alkyl formate and oxalate. The linear a, /J-unsaturated ester 5 is obtained from the terminal alkyne using dppb as a ligand by the reaction of alkyl formate under CO pressure. On the other hand, a branehed ester, t-butyl atropate (6), is obtained exclusively by the carbonylation of phenylacetylene in t-BuOH even by using dppb[10]. Reaction of alkynes and oxalate under CO pressure also gives linear a, /J-unsaturated esters 7 and dialkynes. The use of dppb is essen-tial[l 1]. Carbonylation of 1-octyne in the presence of oxalic acid or formic acid using PhiP-dppb (2 I) and Pd on carbon affords the branched q, /J-unsatu-rated acid 8 as the main product. Formic acid is regarded as a source of H and OH in the carboxylic acids[l2]. 

The most distinctive aspect of the chemistry of acetylene and terminal alkynes is their acidity As a class compounds of the type RC=CH are the most acidic of all hydro carbons The structural reasons for this property as well as the ways m which it is used to advantage m chemical synthesis are important elements of this chapter... 

In the corresponding ionizations of ethylene and ethane the unshared pair occupies an orbital with 33% sp ) and 25% sp ) s character respectively Terminal alkynes (RC=CH) resemble acetylene m acidity... 

Although acetylene and terminal alkynes are far stronger acids than other hydro carbons we must remember that they are nevertheless very weak acids—much weaker than water and alcohols for example Hydroxide ion is too weak a base to convert acety lene to its anion m meaningful amounts The position of the equilibrium described by the following equation lies overwhelmingly to the left... 

The most frequent applications of these procedures he in the preparation of terminal alkynes Because the terminal alkyne product is acidic enough to transfer a proton to amide anion one equivalent of base m addition to the two equivalents required for dou ble dehydrohalogenation is needed Adding water or acid after the reaction is complete converts the sodium salt to the corresponding alkyne... 

We have already discussed one important chemical property of alkynes the acidity of acetylene and terminal alkynes In the remaining sections of this chapter several other reactions of alkynes will be explored Most of them will be similar to reactions of alkenes Like alkenes alkynes undergo addition reactions We 11 begin with a reaction familiar to us from our study of alkenes namely catalytic hydrogenation... 

Acetylene and terminal alkynes are more acidic than other hydrocarbons They have s of approximately 26 compared with about 45 for alkenes and about 60 for alkanes Sodium amide is a strong enough base to remove a proton from acetylene or a terminal alkyne but sodium hydroxide is not... 

The acidity of acetylene and terminal alkynes permits them to be converted to their conjugate bases on treatment with sodium amide These anions are good nucleophiles and react with methyl and primary alkyl halides to form carbon-carbon bonds Secondary and tertiary alkyl halides cannot be used because they yield only elimination products under these conditions... 

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