Acylation of alkynes

Alkynes are readily acylated with acid chlorides under Friedel-Crafts conditions to form, in most cases, fram-p-chlorovinyl ketones through the corresponding vinyl cation intermediate [Eq. (8.16)]. The first study in 1935 reported low yields.11 Later in acylations with acyl triflates, p-keto vinyl triflates were obtained in satisfactory yields.123 When aroyl derivatives are used, the intermediate can undergo cyclization to form indenones. Chlorovinyl ketones formed from terminal alkynes may also react further losing hydrogen chloride to yield conjugated acetylenic ketones 11,13 

Clean formation of a, p-acetylenic ketones could be achieved by carrying out the reaction with a catalytic amount of Cul in the presence of Et3N [Eq. (8.17)]124 or inducing the acylation with a Pd complex and Cul in the presence of Et2NH 125 

An interesting example is the acylation of various terminal acetylenes with preformed acylium tetrafluoroborates in the presence of aromatics 126 

Under the reaction conditions the direct acylation of the aromatic hydrocarbons with the acylium ion does not take place. Instead, the intermediate vinyl carboca-tion reacts with the aromatics to form the 20 aryl-substituted vinyl ketones. 

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Acylation of alkynes, cyclopentenones. Acylation of alkynes with a,a-disubsti-llllotE/f, y-unsaturated acid chlorides, catalyzed with A1C13> results in 5,5-disubstituted-2-cyclopentenones by an unexpected intramolecular cyclization-rearrangement.2 Example ... 

Acylsilanes serve as acyl donors in the Pd-catalyzed cross-couplings with allyl trifluoroacetates,243 aryl halides,244 and alkenyl halides.2 Intramolecular acylation of alkynes with acylsilanes proceeds under catalysis by [RhCl(CO)2]2.246... 

Alkynic ketones have been used extensively in natural product synthesis, due in large part to the contributions of Midland and coworkers and the development of generd methods for enantioselective reduction of this moiety to afford optically active propargyl alcohols using chiral trialkylboranes. Furthermore, the derived alkynic alcohol is a versatile system which can be manipulated directly into cis-or rra 5-allylic alcohols and as a precursor for vinylorganometallic species. This section will briefly cover progress made in the direct acylation of alkynic organolithiums with the acylation protocol d veloped by Weinreb (see also Section 1.13.2.7). 

One final example of acylation of alkynes by lactones forms part of the synthesis of neomethynolide by Yamaguchi. The Prelog-Djerassi lactone serves as the acylating agent (equation 49). The functionalized alkynide undergoes addition very selectively at the lactonic carbonyl group, despite the presence of a relatively unhindered primary ester. ... 

Acylsilanes are available for intramolecular acylation of alkynes under catalysis... 

By comparison with the reactions with aromatic substrates, the absence of the driving force of rearo-matization by proton loss in electrophilic acylations of alkenes leads to competition between alternative pathways for the carbocation intermediate. In particular, capture of halide to form 3-halo ketones can become dominant. Hence, the aliphatic Friedel-Crafts acylation reaction need not necessarily result in substitution of an acyl residue for a hydrogen atom in an alkene, nor in the formation of unsaturated ketones. Indeed, within this broader scope, acylations of alkynes and some classes of alkanes can be synthetically useful. 

The Friedel-Crafts acylation of alkynes is an extremely rapid reaction, and usually leads to the formation of the f/ flni-P-chlorovinyl ketone (equation 23). Reaction temperatures can be as low as -70 °C. The reaction proceeds via reaction of the acyl halide-Lewis acid complex with the alkyne, and whilst the implied vinyl cation has not been observed directly, the reaction products can be understood in terms of reaction of such an intermediate with nucleophiles, usually halide ion. Whilst the r/-an.r-chlorovinyl ketone has been described as the sole product of the reaction by some workers, others have reported the formation of mixtures of the cis and trans forms, under conditions that did not appear to lead to isomeriza-... 

Hydride transfers are implicated in several acylations of alkynes by saturated acyl chlorides leading to cyclopentenes. Intramolecular [1,5] hydride shifts have been shown to be a common feature in silver-assisted reactions of cyclohexanylcarbonyl chloride with alkynes.The nature of the final product depends on the structure of the resulting cation. Capture of fluoride ion, ring contraction and acyl or alkyl migrations of axial substituents have been observed (Scheme 24). 

The formation of a,)0-unsaturated ketones has been modified by the acylation of vinyl mercuric chloride. In addition, this reaction has been extended to the acylation of alkynes and a zinc chloride-promoted acylation of olefins. 

The scope of Friedel-Crafts chemistry has been expanded beyond aromatic systems to nonaromatic systems, such as alkenes and alkynes and the mechanistic details have been investigated. The Friedel-Crafts alkylation and acylation of alkenes provide access to a variety of organic systems (eq 9). The acylation of alkynes provides access to cyclopentenone derivatives (eq 10). In addition, one can use this chemistry to access indenyl systems and vinyl chlorides. AllyUc suHones can undergo allylation chemistry (eq 11). ... 

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