Palladium catalysis Sonogashira

The coupling of terminal alkynes with aryl or vinyl halides under palladium catalysis is known as the Sonogashira reaction. This catalytic process requires the use of a palladium(0) complex, 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 other has hydrogen instead of tin or boron as the metal to be exchanged for palladium. 

The cyclization of 2-alkynylaniline derivatives has become a general method for the assembly of 2-substituted indoles [2, 4]. While a range of other transition metals and Lewis acids can mediate similar intramolecular cyclizations, a useful feature of palladium catalysis is that it can also be employed to assemble the cyclization precursors. The latter is often accomplished by coupling more traditional palladium-catalyzed coupling chemistry with cyclization, and provides an avenue to readily expand the diversity of indole products available. As illustrated with the examples in Scheme 6.5, this can be done via the Sonogashira coupling of 2 with R-X [5], the Stille... 

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]. 

The coupling of terminal alkynes 25 with aryl or vinyl halides under palladium catalysis is known as the Sonogashira reaction. The catalytic process... 

The field of palladium catalysis is also progressing rapidly. The Tsuji-Trost and Mizoroki-Heck reactions have been mentioned earher, however other C-C coupling reactions (Miyaura-Suzuki, Sonogashira and Stille) are now extensively used in organic chemistry, and the search for non-polluting Sonogashira and Miyaura-Suzuki reactions is being actively pursued. 

The original Sonogashira protocol involves palladium-copper co-catalysis. Attempts have been made over the last few years to overcome some of the limitations in this method, specifically to eliminate the undesired dimerization of terminal alkynes. Various copper-free conditions have been developed in order to reduce the amount of diacetylene formation. The focus seems to have been on changing the ligand. 

A. Datta, K. Ebert, H. Plenio, Nanofiltration for homogeneous catalysis separation Soluble polymer-supported palladium catalysts for Heck, Sonogashira, and Suzuki coupling of aryl halides, OrganometaUics 22 (2003) 4685-4691. 

The formation of C-C bonds is one of the important fields of synthetic organic chenustry. Modern methods are in the focus of scientists in academia and industry, often being connected to catalysis. Products based on catalysis represent more than 90% of the total amount of new compounds. Presently, palladium-catalysed reactions play a dominant role. For example, Mizoroki-Heck reactions, as well as Stille, Suzuki, Negishi, Kumada and Sonogashira couplings, are in the standard toolbox of organic chemists [1]. 

Monohgated oxazolines derived from commercially available 2-ethyl-2-oxazoUne can form trans-square-planar palladium complexes by simple treatment of this ligand with inorganic palladium salts in methanolic solutions (Scheme 6.15) [72]. The catalysis, when performed in pyrrolidine, gave a yield of 32%, which corresponded to a TON of 190. The Sonogashira reaction was carried out under aerobic conditions with no precautions to exclude moisture from the solvent or substrates. 

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