Suzuki mechanistic cycle

Scheme 10. Proposed mechanistic cycle for Suzuki-Miyaura cross-coupling based on tbe observation of binuclear palladium complexes. L=l.l -(cyclohexylpbospbanediyl)dipiperidine.

Scheme 6 Possible mechanistic cycles for Suzuki-Miyaura reactions...

Scheme 2.49 Proposed mechanistic cycle of the Ni-catalyzed stereoconvergent Suzuki-Miyaura cross-coupling reactions.

Most of the mechanistic work on this reaction has been devoted to determining the role of the base. Its most obvious function would be to complex the Lewis-acidic boron reagent, rendering it nucleophihc and thus activating it toward transmetallation. However, Miyaura, Suzuki, and coworkers noted that an electron-rich tetracoordinate boronate complex was less reactive than a bivalent boronic ester. From this, they surmised that the role of the base was not to activate the boron toward transmetallation, but rather to transform the palladium halide intermediate to the hydroxide or alkoxide species, which would then be more reactive toward boron. However, in a mass spectrometry study of a reaction between a pyridyl halide substrate and an aryl boroiuc acid, Aliprantis and Canary saw no evidence of palladium hydroxide or alkoxide intermediates, despite observing signals in the mass spectra assignable to every other palladium intermediate of the proposed catalytic cycle. ... 

The Suzuki reaction has already found a first industrial application [24], after the catalyst Pd(TPPTS)a n HaO became available [25], In a two-phase procedure, the water-soluble catalyst effects the C-C coupling of arylboronic acis with aryl chlorides to form pharmaceutical intermediates. The Suzuki C-C cross-coupling is on the way to industrial perfection. Since the basic mechanistic features are clear by now, it is desirable that the catalysts are easy to prepare, easy to handle, and cheap, and that they bear cr-donor type ligands of which at least one does not dissociate from the metal throughout the catalytic cycle. Thus the Suzuki coupling will be seen in the syntheses of a growing number of fine chemicals and pharmaceuticals in due course. 

Owing to the low nudeophihdty of the borane reagents (compared with organo-stannanes, for example), the Suzuki-Miyaura, reaction in order to take place, requires the addition of a base. Stronger bases such as NaOH, HOH, and NaOMe perform well in THF/H2O solvent systems, whereas weaker bases such as KjCOj and K3PO4 are usually more successful in DMF. The base is involved in several steps of the catalytic cycle, most notably in the transmetallation process. Soderquist [259] performed detailed mechanistic studies on the coupling of trialkylboranes and alkoxy(dialkyl)boranes with aryl and alkenyl electrophiles (Scheme 1.34). 

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