The Suzuki-Miyaura cross-coupling reaction involves the formation of a carbon–carbon bond between an organoboron nucleophile and an organohalide or -pseudohalide electrophile in the presence of a transition metal catalyst. Although early reports of this reaction described catalysts containing palladium, more earth-abundant metals such as iron, copper, and nickel can also be employed. The scope of Suzuki-Miyaura cross-coupling is extremely broad: alkyl-, alkenyl-, alkynyl-, aryl-, and heteroarylboron reagents may be used as nucleophiles and the scope of the electrophile includes alkynyl, alkenyl, aryl, and heteroaryl halides with few limitations. The broad scope and exceptional utility of this reaction have resulted in its widespread adoption as a tool for forging carbon–carbon bonds in organic synthesis.
The mechanism of the Suzuki-Miyaura cross-coupling reaction involves three general stages: oxidative addition of the organo(pseudo)halide to the transition metal catalyst (most often a palladium(0) species), transmetalation of the organoboron reagent, and reductive elimination of the organic product, which contains a new bond between the carbon linked to the boron group in the nucleophile and the carbon linked to the halide or pseudohalide group in the electrophile. Oxidative addition is accelerated by electron-rich ligands linked to the metal catalyst and is generally most rapid for organoiodides and -triflates. Transmetalation may proceed through two pathways. During the “oxo-palladium” pathway, hydroxide (or alkoxide) displaces a leaving group linked to palladium, yielding a palladium(II) hydroxide species. A sigma-bond metathesis process then results in transfer of an organic group to palladium and elimination of a species containing a new boron–oxygen bond. During the “organoboronate” pathway, the Lewis basic oxygen coordinates to boron before palladium. After this oxygen atom coordinates to palladium and displaces the (pseudo)halide, sigma-bond metathesis occurs. The oxo-palladium pathway is typical of most Suzuki-Miyaura reactions, with only the most Lewis basic organoboron reagents reacting through the organoboronate pathway. Following transmetalation, reductive elimination regenerates a palladium(0) species and gives the coupled organic product. Reductive elimination is most rapid from tricoordinate complexes of the form LPdRM1R2; consequently, sterically bulky ligands that promote the loss of a ligand molecule from a tetracoordinate species accelerate this step.