The Cu-Free Sonogashira Reaction

Over the last years, two reaction mechanisms proposed for the copper-free Sonogashira reaction have been somewhat discussed in the literature. Recently, the experimental group of Martensson demonstrated that one of them can be discarded, and further proposed two alternatives for the other mechanism on the basis of the electronic nature of the alkyne s substituents. Hence, in order to shed light on the reaction mechanism for this process, we decided to carry out a theoretical study in close contact with the experimental group of Prof. Carmen Nijera with the following main objectives  

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Scheme 9.7 Proposed mechanism of the Cu-free Sonogashira reaction (the so-called Heck-Cassar coupling) [25].

Scheme 9.16 Pd-free version of the Sonogashira reaction relying on the N,0-bifunctional Cu catalyst 50 [152].

Aryl and alkyl-substituted diynes and tetraynes have been synthesized in good yields (82-99%) by TBAF-promoted desily-lation and Cu-catalyzed oxidative dimerization of triisopropylsi-lyl (TlPS)-protected acetylenes (eq 38). Copper acetate was used as oxidant in this reaction. Aryl- and alkenyl alkynes were made under similar conditions (eq 39). Pd/C with TBAF was used in ligand- and copper-free, one-pot, domino Halex-Sono-gashira reactions. Similarly, TBAF promoted the synthesis of 2-substituted indoles by a tandem Sonogashira/cyclization reaction of 2-iodoanilines and terminal alkynes. ... 

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