Sonogashira coupling reaction mechanisms

Scheme 14. (a) Sonogashira cross-coupling reaction mechanism, (b) Click chemistry [2 + 3]... 

The mechanism of the Sonogashira reaction has not yet been established clearly. This statement, made in a 2004 publication by Amatore, Jutand and co-workers, certainly holds much truth [10], Nonetheless, the general outline of the mechanism is known, and involves a sequence of oxidative addition, transmetalation, and reductive elimination, which are common to palladium-catalyzed cross-coupling reactions [6b]. In-depth knowledge of the mechanism, however, is not yet available and, in particular, the precise role of the copper co-catalyst and the structure of the catalytically active species remain uncertain [11, 12], The mechanism displayed in Scheme 2 includes the catalytic cycle itself, the preactivation step and the copper mediated transfer of acetylide to the Pd complex and is based on proposals already made in the early publications of Sonogashira [6b]. 

Bohm, V. P. W., Herrmann, W. A. Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions, 13 a copper-free procedure for the palladium-catalyzed Sonogashira reaction of aryl bromides with terminal alkynes at room temperature. Eur. J. Org. Chem. 2000,3679-3681. 

Scheme 12.22 shows the generally accepted mechanism for Sonogashira coupling. It features three interconnecting cycles.150 Cycle a lies at the heart of the mechanism and should by now be quite familiar. Cycle b shows a plausible scheme for converting Pd(II) complexes, the usual form of the precatalyst, to Pd(0). Other mechanisms for this reduction may apply, however, especially since tertiary amine bases are commonly present in the reaction (see Section 12-3-2). Cycle c connects with cycle a, and it suggests how Cu catalyzes the formation of the Cu-alkyne, which then transmetalates with Pd. 

In copper-free Sonogashira coupling the competition of ligand and amine base determines the reaction mechanism. The oxidative addition of Arl with (Ph3P)4Pd is faster when amine is present. With the proposed mechanisms the efficiency of PhsP > PhsAs is explained. 

RBA values were also measured for ERp and were usually lower. To achieve optimal synthetic yields, the mechanisms of a range of palladium coupling reactions (Sonogashira, Stille) were investigated [139]. 

Scheme 1.8 (a) General conditions for the Songashira-Hagihara cross-coupling reaction, (b) The proposed mechanism for the Sonogashira-Hagihara cross-coupling arylation procedure [12, 24]. 

The Sonogashira cross-coupling reaction, consisting of oxidative addition, cis-trans isomerization, transmetallation and reductive elimination has been modelled, using the DFT B3LYP/cc-pVDZ method, for Pd(diphosphane)-catalysed reaction between bro-mobenzene and phenylacetylene with CuBr as a co-catalyst and trimethylamine as a base. The reaction mechanism in both the gas phase and in CH2CI2 solution has been studied using the polarized continuum model (PCM) method. ... 

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