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Direct functionalization of the C(O)–N amide bond is one of the most high-profile research directions in the last few decades; however oxidative couplings involving amide bonds and functionalization of thioamide C(S)–N analogues remain an unsolved challenge. Herein, a novel hypervalent iodine-induced twofold oxidative coupling of amines with amides and thioamides has been established. The protocol accomplishes divergent C(O)–N and C(S)–N disconnection by the previously unknown Ar–O and Ar–S oxidative coupling and highly chemoselectively assembles the versatile yet synthetically challenging oxazoles and thiazoles. Employing amides instead of thioamides affords an alternative bond cleavage pattern, which is a result of the higher conjugation in thioamides. Mechanistic investigations indicate ureas and thioureas generated in the first oxidation as pivotal intermediates to realize the oxidative coupling. These findings open up new avenues for exploring oxidative amide and thioamide bond chemistry in various synthetic contexts. 

The activation of C–O bonds in aryl methyl ethers is a fundamental method for the cross-coupling of carbon–oxygen bonds; however, this process is highly challenging due to the high dissociation energy compared with other phenol derivatives. Herein, we report a mild Ru(0)-catalyzed cleavage of C(aryl)–O bonds enabled by a combination of a Ru 3 (CO) 12 catalyst and an imine auxiliary. This method offers rapid entry to synthetically valuable biaryl aldehydes from abundant anisoles. Broad functional group tolerance is observed using this strategy, including unprecedented tolerance towards aryl bromides. The synthetic utility of this strategy has been demonstrated in sequential processes to construct complex biaryls, exploiting the orthogonal selectivity of C–O bond activation. DFT studies were conducted to provide insight into the selectivity of C–O bond cleavage. This method establishes the mildest approach to C–OMe cross-coupling reported to date. 

We report the synthesis, characterization and reactivity of an air-stable, well-defined acenaphthoimidazolylidene palladium–BIAN–NHC chloro dimer complex, [Pd(BIAN–IPr)(μ-Cl)Cl] 2 . This rapidly activating catalyst merges the reactive properties of palladium chloro dimers, [Pd(NHC)(μ-Cl)Cl] 2 , with the attractive structural features of the BIAN framework. [Pd(BIAN–IPr)(μ-Cl)Cl] 2 is the most reactive Pd( ii )–NHC precatalyst discovered to date undergoing fast activation under both an inert atmosphere and aerobic conditions. The catalyst features bulky-yet-flexible sterics that render the C–H substituents closer to the metal center in combination with rapid dissociation to monomers and strong σ-donor properties. [Pd(BIAN–IPr)(μ-Cl)Cl] 2 should be considered as a catalyst for reactions using well-defined Pd( ii )–NHCs. 

Over the last 20 years, N-heterocyclic carbenes (NHCs) have emerged as a dominant direction in ligand development in transition metal catalysis. In particular, strong σ-donation in combination with tunable steric environment make NHCs to be among the most common ligands used for C–C and C–heteroatom bond formation. Herein, we report the study on steric and electronic properties of thiazol-2-ylidenes. We demonstrate that the thiazole heterocycle and enhanced π-electrophilicity result in a class of highly active carbene ligands for electrophilic cyclization reactions to form valuable oxazoline heterocycles. The evaluation of steric, electron-donating and π-accepting properties as well as structural characterization and coordination chemistry is presented. This mode of catalysis can be applied to late-stage drug functionalization to furnish attractive building blocks for medicinal chemistry. Considering the key role of N-heterocyclic ligands, we anticipate thatN-aryl thiazol-2-ylidenes will be of broad interest as ligands in modern chemical synthesis.

 

Thioamides are ‘single-atom’ isosteres of amide bonds that have found broad applications in organic synthesis, biochemistry and drug discovery. In this New Talent themed issue, we present a general strategy for activation of N–C(S) thioamide bonds by ground-state-destabilization. This concept is outlined in the context of a full study on transamidation of thioamides with nucleophilic amines, and relies on (1) site-selective N -activation of the thioamide bond to decrease resonance and (2) highly chemoselective nucleophilic acyl addition to the thioamide CS bond. The follow-up collapse of the tetrahedral intermediate is favored by the electronic properties of the amine leaving group. The ground-state-destabilization concept of thioamides enables weakening of the N–C(S) bond and rationally modifies the properties of valuable thioamide isosteres for the development of new methods in organic synthesis. We fully expect that in analogy to the burgeoning field of destabilized amides introduced by our group in 2015, the thio amide bond ground-state-destabilization activation concept will find broad applications in various facets of chemical science, including metal-free, metal-catalyzed and metal-promoted reaction pathways.