Selective Palladium‐Catalyzed Suzuki–Miyaura Reactions of Polyhalogenated Heteroarenes

Abstract

The palladium-catalyzed Suzuki-Miyaura reaction of multiply halogenated, electron-rich and electron-deficient heteroarenes is one of the most reliable and environmentally friendly tools for installing a wide range of non-functionalized and functionalized carbon substituents onto heteroaromatic systems with exquisite chemo-and site-selectivity. For substrates with different halogen groups the chemoselectivity of the Suzuki-Miyaura reactions has been found to be dependent on the reactivity difference between the halogens. However, the hardest achievement of selectivity in Suzuki-Miyaura monocouplings involving polyhalogenated heteroarenes with identical halogen atoms has been shown to be dominated by steric and electronic effects and the presence of directing groups at positions neighbouring the reaction sites. Moreover, in the case of symmetrically substituted dihaloheteroarenes with identical halogen atoms, highly selective monocoupling reactions have often been achieved only after a careful optimization of reaction parameters including the catalyst precursor, base, solvent, and the molar ratio between electrophile and organoboron reagent. This critical review with 341 references covers developments on the chemo-and site-selective Suzuki-Miyaura monocoupling reactions of polyhalogenated heteroarenes with different or identical halogen atoms. It also includes the synthesis of polysubstituted heteroarenes, not easily accessible by other means, via consecutive monocoupling reactions and/ or a more synthetically valuable approach involving one-pot polycoupling reactions.

Rapid Room‐Temperature, Chemoselective C−C Coupling of Poly(pseudo)halogenated Arenes Enabled by Palladium(I) Catalysis in Air

“…The biaryl motif is not only present in numerous drug molecules,b ut it is also au biquitous building block in materials science and complex natural products.I ts substitution pattern ultimately determines the function as pharmaceutical, agrochemical, electronic device,s econdary metabolite,o re ven privileged ligand. While the relative ease of oxidative addition is frequently referred to as C À I > C À OTf % C À Br > C À Cl, [2] these rough trends by no means allow an ap riori prediction of favored coupling site.Instead, it is aresult of subtle interplay between substrate (electronic/steric bias and bond strength), catalyst (ligand/ligation state), solvent, and additive effects ( Figure 1). Owing to the relative mildness,p alladium-catalyzed chemoselective crosscoupling strategies of poly(pseudo)halogenateda renes represent astrategy of considerable interest.…”

“…[1] Consequently,t he development of as ynthetic repertoire to selectively access diversely functionalized arenes is of considerable interest. [2,3] Fore xample,w hile [PdCl 2 {P(o-tol) 3 } 2 ]-catalyzed Kumada coupling of A gave selective C À Br functionalization, the introduction of two methyl groups ortho to C À Br (B)d iminished selectivities,t hus resulting in mixtures under otherwise identical reaction conditions ( Figure 1). [2] In this context, the oxidative addition step is generally selectivity-controlling.…”

A General and Practical Palladium‐Catalyzed Direct α‐Arylation of Amides with Aryl Halides

“…18b In general, aryl chlorides are less reactive than aryl bromides in cross-coupling reactions. 32 Nevertheless, aryl chlorides are less expensive and more abundant, so their use in the cross-coupling reactions is highly desirable. In the original report by the Hartwig group, BINAP was employed as ligand.…”

Aziridine- and Azetidine-Pd Catalytic Combinations. Synthesis and Evaluation of the Ligand Ring Size Impact on Suzuki-Miyaura Reaction Issues

“…This reaction has become for decades a major methodological tool available to chemists to build molecular architectures especially based on a biaryl scaffold. The biaryl motif can be found in numerous natural products, agrochemicals, drugs, polymers, ligands and thus triggered the attention of the scientific community for a wide range of applications [2][3][4][5][6][7][8][9]. If the formation of a biphenyl motif belongs nowadays to a textbook knowledge, the past decade has witnessed spectacular innovations and improvements such as ligandless transformations [10], supported or nanostructured catalytic systems [11][12][13], performing additives [14,15], neat and/or aqueous conditions [2,13,15], MW activations [10] for example.…”