Suzuki reaction mechanisms

The mechanism " of the Suzuki reaction is closely related to that of the Stille coupling reaction, and is also best described by a catalytic cycle ... 

Scheme 6.11 Proposed mechanism for the formation of palladium-imidazolylidene species under the conditions employed in Suzuki reactions...

In each case, the mechanism involves generation of an aryl radical from a covalent azo compound. In acid solution, diazonium salts are ionic and their reactions are polar. When they cleave, the product is an aryl cation (see p. 856). However, in neutral or basic solution, diazonium ions are converted to covalent compounds, and these cleave to give free radicals (Ar and Z"). Note that radical reactions are presented in Chapter 14, but the coupling of an aromatic ring with an aromatic compound containing a leaving group prompted its placement here. Note the similarity to the Suzuki reaction in 13-12. 

A -unsubstituted 4,5-dichloropyridazin-3(277)-one (109) fails to undergo Suzuki crosscoupling reactions. In order to synthesize N-2, unsubstituted 4,5-diarylpyridazin-3(2//)-ones (112) by Suzuki reaction, the temporary protection of the lactam moiety of 109 is essential. To achieve this a simple and efficient retro-ene-assisted Suzuki methodology has been developed by Ravina and co-workers which is based on 4,5-dichloro-2-(hydroxymethyl)pyridazin-3(277)-one (110) [61]. This pyridazin-3(2//)-one is easily available from 109 via reaction with formaldehyde. Interestingly, 110 reacts smoothly with arylboronic acids to afford directly the deprotected 4,5-diarylated pyridazin-3(2//)-ones (112) in high yields. The mechanism probably involves the formation of 4,5-diarylated-2-(hydroxymethyl)pyridazin-3(277)-ones (111), which subsequently lose formaldehyde by a retro-ene reaction induced by base or heat [62]. 

Adachi K, Suzuki I (1977) A study on the reaction mechanism of adenosine-5 -phosphate reductase from Thiobacillus thiopams, an iron-sulfur protein. Can J Biochem 55 91-98... 

A further orthogonal strategy compatible with peptide and many other organic synthesis is offered by allyl-functionalized anchors. The mechanism of release is depicted in Figure 5.8, and involves the use an intermediate Pd-complex with the double bond [267,268], Recent developments use Pd-catalyzed metathesis techniques to cleave unsaturated anchors in inter- and intramolecular reactions. An unsaturated tin-anchor has been used to achieve cleavage with an intramolecular Suzuki reaction. 

Although this study did not provide quantitative or detailed structural information about the intermediates, it was able to analyze the reaction mixture and observe mass spectra that correspond to the two key intermediates in the proposed mechanism for the Suzuki reaction. These results demonstrate that ESI-MS can be a valuable mechanistic tool when used in conjunction with other techniques. 

Of all the chemical processes which were reviewed and described in references [1-3], it should be noted that up to now only the Kovacic and Yamamoto reactions and, to a lesser extent, the thermal dehydrogenation of poly(l,3-cyclohexadiene) have been used to synthesize polyphenylenes for usual or special applications. Only recently, a new impulse has been given to the synthesis of linear functionalized high molecular-weight PPPs with the adaptation of the Suzuki reaction, and this is currently one of the best possible ways of synthesizing soluble, functionalized PPPs for specific applications with, in particular, the realization of rigid rod-like polymers for mechanical applications, as will be shown in Section 2.1.3. 

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