Halides, aryl, with active Sonogashira

Sonogashira has proposed a catalytic cycle (Figure 4) which shows 1) the reduction of the palladium complex, 2) coordination of the aryl halide and acetylene with the palladium (0) complex and 3) the reductive elimination of the substituted aryl acetylene and regeneration of the active catalyst.(10)... 

Hierso et al reported a copper-free, Sonogashira reaction for a number of activated and deactivated aryl halides with alkyl-/aryl acetylenes and using a variety of metallic precursors, bases and tertiary phosphanes in [bmim][BF4]. They found that a combination of [Pd(/7 -C3H5)Cl]2/PPh3 with 1 % pyrrolidine in the absence of copper showed the highest activity. 

The mechanism of the Sonogashira cross-coupling follows the expected oxidative addition-reductive elimination pathway. However, the structure of the catalytically active species and the precise role of the Cul catalyst is unknown. The reaction commences with the generation of a coordinatively unsaturated Pd species from a Pd " complex by reduction with the alkyne substrate or with an added phosphine ligand. The Pd " then undergoes oxidative addition with the aryl or vinyl halide followed by transmetallation by the copper(l)-acetylide. Reductive elimination affords the coupled product and the regeneration of the catalyst completes the catalytic cycle. 

The coupling of terminal alkynes with aryl or vinyl halides under palladium catalysis is known as the Sonogashira reaction and is rather like the Heck reaction. It is a catalytic process, requiring a palladium(O) complex it is performed in the presence of base, and generally uses copper iodide as a co-catalyst. One partner—the aryl or vinyl halide—is the same as in the Stille and Suzuki couplings but the alkyne needs no metal to activate it the reaction works with the alkyne itself. 

As we have commented earlier, there are some reports in where polymers are used to act as interface between the metal NPs and the G support increasing the adherence of the metal NPs to Gs. In one of these examples polypropylene imine dendrimer has been used to increase the stability of Pd-Co alloy NPs on r-GO (Scheme 3.42). This dendrimer modified r-GO catalyst is able to promote the Sonogashira coupling of alkynes and aryl halides using K COj at 25 °C. Importantly metal leaching was not observed and as a reflection of the catalyst stability, the material could be reused six times with the catalytic activity decreasing only from 99 to 93 % after the sixth cycles. 

With the development of Buchwald-Hartwig amination reactions, the amine component of these indoles can also be introduced into these precursors via palladium catalysis [8]. As shown by Ackermann, this can be coupled with aryl halide alkynylation and cyclization to provide a one-pot, three-component synthesis of substituted indoles (Scheme 6.6) [9]. In this case, simple ortho-dihaloarene derivatives S were employed as starting materials, with Sonogashira coupling occurring at the more activated aryl-iodide bond, followed by selective coupling of various alkyl or arylamines. Alternatively, Zhao has recently demonstrated that amination can be performed on both bromoalkyne 6, followed by the aryl-bromide bond, to provide a route to 2-amidoindoles (Scheme 6.7) [10]. 

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