Direct alkynylation reaction mechanism

The direct palladium-catalyzed C3-alkynylation of free indoles with bromoacety-lenes was first described by Gu and Wang in 2009. The C2-selective alkynylation of indole proved to be especially challenging, and this was not realized until Waser et al. described a mild protocol using TIPS-protected hypervalent iodine reagent 101 and a palladium(II) catalyst (Scheme 10.34). Under optimized conditions, a variety of 7V-alkylated indoles 100 could undergo the alkynylation reaction via a palladium(II)/palladium(IV) mechanism to afford products 102-106 in moderate to good yields. It is unknown whether the C2-palladated intermediate is formed as result of a CMD mechanism, or via a pathway of electrophilic palladation at C3 followed by metal migration to C2. 

The reactions of / -ketoethynyl- and ) -amidoethynyl(phenyl)iodonium triflates, 17 and 18, with sodium / -toluenesulfinate illustrate the synthetic potential of alkynyliodonium salts33. Although the direct attachment of a carbonyl group to the / -carbon atom of the triple bond in alkynyliodonium ions might be expected to facilitate alkynyl sulfone formation via the Ad-E mechanism, this mode of reactivity has not been observed. Instead, the MC pathway with carbenic insertion dominates and affords sulfones containing the... 

Terminal alkynes can be coupled directly to aryl and to vinyl halides in the presence of a palladium catalyst and a base. The mechanism of this reaction appears to involve oxidative addition of the sp halide to palladium(O), followed by alkynylation of the intermediate organopalladium halide and reductive elimination of the disubstituted alkyne (equations 17 and... 

For alkynyl transfer, no direct evidence has been presented to determine whether organometallic nucleophiles interact with the electrophilic iodine centre or the jS-carbon although, in the case of transfer to the nitrogen nucleophile of a coordinated cyano ligand, the S-interaction mechanism is clearly implicated in the formation of 68 (Scheme 38, related to the mechanism in Scheme 14). This example indicates, for the synthesis of alkynylmetal species, the attractiveness of RC=C(Ph)I reagents where the R group cannot participate in such reactivity, e.g. R = SiMcs, Ph. Alternatively, this type of reaction, where the metal centre may act as a nucleophile at the -carbon, is worthy of exploration as a mode of organometallic synthesis as also is electrophilic attack at the K-carbon of ylides (illustrated by the mechanism in Scheme 14). 

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