Acetylenic carbon, substitution nucleophilic

Table 28. Synthesis via nucleophilic substitution at an acetylenic carbon ... 

Additions to Unsaturated Phosphonium Salts. In a review of nucleophilic substitution at acetylenic carbon, attention has been drawn to the synthetic potential of alkynyl-phosphonium salts, e.g. (140), which have received little study so far. ... 

Fujii, A., Dickstein, J.I., and Miller. S.L. Nucleophihc substitution at an acetylenic carbon. Carbon vs. halogen attack by phosphorus nucleophiles. Tetrahedron Lett.. 11, 3435, 1970. 

The question of the mechanism(s) of nucleophilic substitution at the acetylenic carbon atom is an important one and has been investigated and discussed for a long time. For leading references, see [4] and A. Fujii, J. I. Dickstein, S. 1. Miller, Tetrahedron Lett. 1970,39, 3435-3438 and references cited therein R. Tanak, M. Rodgers, R. Simonaitis, S. I. Miller, Tetrahedron 1971,27, 2651-2659 A. Commercon, J. F. Normant, J. Villiers, Tetrahedron 1980, 36, 1215-1221. 

The unsubstituted carbon-carbon triple bond, by virtue of its tt-bonds, is electron-rich and hence generally not disposed toward interaction with other electron-rich species. Therefore, even acetylenes bearing a leaving group, such as haloalkynes, do not undergo the direct S -l or Sn-2 type of nucleophilic displacement reactions. In fact the parent alkynyl cation, HC/, is estimated to be some 60 kcal/mol less stable than the methyl cation [1]. As a consequence the vast majority, if not all, nucleophilic substitutions at an acetylenic carbon occur via some type of addition-elimination process [2, 3]. 

Nucleophilic substitution of halogen at an acetylenic carbon in principle represents another general approach to acetylenic ethers (equation 45). 

Each alkyne can be synthesized by alkylation of an appropriate alkyne anion. First decide which new carbon-carbon bond or bonds must be formed by alkylation and which alkyne anion nucleophile and haloalkane pair is required to give the desired product. Synthesis of a terminal alkyne from acetylene requires only one nucleophilic substitution, and synthesis of an internal alkyne from acetylene requires two nucleophilic substitutions. 

Nucleophilic Displacement at Acetylenic Carbon.— Among studies of nucleophilic displacement at acetylenic carbon are the reactions of phosphines and amines with halogenoacetylenes. Using phosphines, displacement occurs by competitive attack on halogen and carbon the general order of reactivity in substitution at carbon by phosphine nucleophiles is sp <- sp > sp. In... 

Other Reactions of Acetylenes.—Several recent papers have been concerned with the mechanism of nucleophilic displacement at acetylenic carbon. In the halide displacement from halogenoacetylenes, substitution is feasible by either a-addition and / -elimination [reaction (4)] or by attack on the halogen atom with subsequent attack by the acetylide anion [reaction (5)]. 

S. L. Miller and J. I. Dickstein, Nucleophilic Substitution at Acetylenic Carbon. The Last Holdout , Accounts Chem. Res., 1976, 9, 358. 

This intramolecular nucleophilic acyl substitution reaction of acetylenic carbonates proceeds similarly to afford lactones or a,/3-unsaturated esters after hydrolysis of the resulting titanium complexes (Scheme 12.62) [81]. This sp organotitanium species 94 can also be trapped with an aldehyde, which easily undergoes recycliza-tion to give a substituted butenolide after acidic workup. 

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. 

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... 

That the substitution mechanism depends on the nature of the nucleophile is shown by the formation of the ketene acetals (151) from the reaction of vinylidene chloride with alkoxide ions. It was suggested that two consecutive eliminations-additions take place, and that in both cases the alkoxide attacks the acetylene at the substituted carbon (Kuryla and Leis, 1964). Since chloroacetylene (132) is also an inter-... 

Additionally, acetylene itself is a useful two-carbon building block but is not very convenient to handle as it is an explosive gas. Trimethylsilyl acetylene is a distillable liquid that is a convenient substitute for acetylene in reactions involving the lithium derivative as it has only one acidic proton. The synthesis of this alkynyl ketone is an example. Deprotonation with butyl lithium provides the alkynyl lithium that reacted with the alkyl chloride in the presence of iodide as nucleophilic catalyst (see Chapter 17). Removal of the trimethylsilyl group with potassium carbonate in methanol allowed further reaction on the other end of the alkyne. 

The acetylide ion is a strongly basic and nucleophilic species which can induce nucleophilic substitution at positive carbon centres. Acetylene is readily converted by sodium amide in liquid ammonia to sodium acetylide. In the past alkylations were predominantly carried out in liquid ammonia. The alkylation of alkylacetylenes and arylacetylenes is carried out in similar fashion to that of acetylene. Nucleophilic substitution reactions of the alkali metal acetylides are limited to primary halides which are not branched in the -position. Primary halides branched in the P-position as well as secondary and tertiary halides undergo elimination to olefins by the NaNH2. The rate of reaction with halides is in the order I > Br > Cl, but bromides are generally preferred. In the case of a,o)-chloroiodoalkanes and a,to-bromoiodoalkanes. 

Unsaturation at the a Carbon. Vinylic, acetylenic, and aryl substrates are very unreactive toward nucleophilic substitutions. For these systems, both the SnI and Sn2 mechanisms are greatly slowed or stopped altogether. One reason that has been suggested for this is that sp (and even more, sp) carbon atoms have a higher electronegativity than sp carbons and thus a greater attraction for the electrons of the bond. As we have seen (p. 388), an p-H bond has a higher acidity than an H bond, with that of an sp H bond in... 

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