Jin Zhang

Mechanochemical activation represents a powerful concept to harness mechanical force and drive chemical transformations in a solid state. Herein, we report a framework to determine the effect of temperature increase on mechanochemical ball milling in Rh(I)-catalyzed C−H/C−N activation. By using collision dynamics, we provide a model to determine the effect of ball size, milling frequency, internal jar length, velocity, material, and internal curvature during the collisions. By conducting computational studies, we investigate the reaction mechanism and the role of thermal mechanochemical collisions on C−H/C−N bond activation steps. Taking the solution-phase mechanism as a working hypothesis, the observed ball-milling acceleration is consistent with a proposal combining local temperature elevation at impact sites, estimated at up to 83.5 K above the bulk temperature, and modest, step-dependent mechanical modulation of selected transition states, while the rate-determining step is not significantly affected by compression. These results suggest that mechanical force can lower selected transition-state barriers at hot spots, offering a promising strategy for mechanochemical synthesis.

Direct decarbonylative N–C(O)/C–H activation of amides with indoles has been achieved under Rh(I)-catalyzed mechanochemical conditions. The method exhibits a broad substrate scope, furnishing a diverse array of valuable 2-arylindoles by exploiting ubiquitous amide bonds in high yields and providing an entryway for late-stage functionalization of pharmaceuticals containing amides. Crucially, mechanochemical conditions operate at 90 °C in the absence of solvents, bases, and additives, permitting a substantially lower temperature for decarbonylative N–C(O) activation by a sustainable approach.

Direct decarbonylative triple C-N, C-C, and C-H functionalization of amides with hydrocarbons has been accomplished under mechanochemical conditions via Rh(I) catalysis. This method exhibits excellent substrate versatility in high-yielding couplings with diverse aromatic compounds, and its utility is highlighted by late-stage pharmaceutical derivatization and orthogonal C-X and C-N sequential cross-couplings. This solvent-free mechanochemical approach drastically lowers the temperature required for triple amide activation, overcoming kinetic barriers through a sustainable pathway.

A highly selective Au( i )–NHC-catalyzed (NHC = N-heterocyclic carbene) addition of acyl hydrazines to alkynes made feasible by the development of gold( i ) complexes of “half-umbrella” shaped thiazole-derived N-heterocyclic carbenes is reported.

This study introduces a new class of (NHC)Pd(allyl)Cl complexes featuring thiazol-2-ylidene ligands, which exhibit enhanced steric and electronic properties compared to those of traditional imidazol-2-ylidenes. These air-stable Pd(II)-NHC catalysts demonstrate superior reactivity in chemoselective Suzuki-Miyaura cross-couplings of aryl bromides and amides. Kinetic studies reveal their superior reactivity over traditional imidazol-2-ylidene-based complexes. The findings highlight the potential of thiazole-based carbenes in advancing Pd-catalyzed cross-coupling reactions.

Air- and moisture-stable cationic homoleptic Cu( i )–thiazol-2-ylidene complexes are developed as highly efficient σ-Lewis acid catalysts.

This work demonstrates Cu-NHC (NHC = N-heterocyclic carbene) catalyzed alkynylation of aryl thianthrenium salts via thiazol-2-ylidene ligands, achieving a Pd-free Sonogashira coupling with broad substrate compatibility and functional group tolerance. Late-stage pharmaceutical alkynylation and rare alkynylative C-H functionalization/ring-opening pathways are enabled. Thiazol-2-ylidenes, featuring a "half-umbrella"-shaped geometry, exhibit superior catalytic performance over traditional imidazol-2-ylidenes, underscoring their unique ligand efficacy. Cu-NHC catalysis enables the use of aryl thianthrenium salts as versatile electrophiles for diverse cross-couplings under mild conditions.

A new method for chemoselective transition-metal-free acylation of thioamides with ketones by N–C(S) bond cleavage is reported.