Abstract
Pd-catalyzed, site-selective mono-cross-coupling of substrates with two identical halo groups is a useful method for synthesizing substituted monohalogenated arenes. Such arenes constitute an important class of compounds, which are commonly identified as drug components and synthetic intermediates. Traditionally, these site-selective reactions have been realized in a “substrate-controlled” manner, which is based on the steric and electronic differences between the two carbon-halogen bonds of the substrate. Recently, an alternative strategy, “catalyst-controlled” site-selective cross-coupling, has emerged. In this strategy, the preferred reaction site of a dihaloarene can be switched, merely by changing the catalyst used. This type of selective reaction further expands the utility of Pd-catalyzed cross-coupling. In this review, we summarize the reported examples of catalyst-controlled site-selectivity switching in Pd-catalyzed cross-coupling of dihaloarenes.
Highlights
Pd-catalyzed cross-coupling of haloarenes with organometallic reagents constitutes one of the most important and practical reactions in transition metal-catalyzed carbon-carbon bond formations [1,2,3]
In comparison with the chemoselective cross-coupling, it is difficult to achieve siteselective cross-coupling of substrates where both halo groups are the same. Because these substrates can generally be prepared in shorter steps than the compounds with two different halo groups, this type of site-selective cross-coupling can prove more useful for the synthesis of multisubstituted arenes [12,13,14,15]
The choice of appropriate catalyst ligands is the key to controlling site-selectivity. These ligands coordinate with palladium and affect which of the two carbon-halogen bonds is preferred in oxidative addition, the step generally considered to be the irreversible, selectivity-determining step in these cross-coupling reactions (Scheme 2), reversible oxidative addition was observed in some cases [20]
Summary
Pd-catalyzed cross-coupling of haloarenes (or pseudo-haloarenes, such as aryl triflates) with organometallic reagents constitutes one of the most important and practical reactions in transition metal-catalyzed carbon-carbon bond formations [1,2,3]. The majority of examples for the site-selective cross-coupling of dihaloarenes reported so far are based on the “substrate-controlled” strategy, which relies on the different reactivity of the two carbon-halogen bonds in the substrate. An alternative “catalyst-controlled” strategy for site-selective cross-coupling has emerged In this strategy, the reaction site of a dihaloarene can be controlled by the catalyst used, regardless of the intrinsic reactivity of the halo groups in the substrate. The choice of appropriate catalyst ligands is the key to controlling site-selectivity These ligands coordinate with palladium and affect which of the two carbon-halogen bonds is preferred in oxidative addition, the step generally considered to be the irreversible, selectivity-determining step in these cross-coupling.
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