A general class of well-defined, air-stable, and readily available Pd(II)-NHC precatalysts (NHC = Nheterocyclic carbene) for Suzuki and Buchwald−Hartwig cross-coupling of amides (transamidation) and esters by selective N−C/O−C cleavage is reported. Since these precatalysts are highly active and the easiest to synthesize, the study clearly suggests that [Pd(NHC)(acac)Cl] should be routinely included during the development of new crosscoupling methods. An assay for in situ screening of NHC salts in this cross-coupling manifold is presented.

Summary The development of more reactive, general, easily accessible, and readily available Pd(II)–NHC precatalysts remains a key challenge in homogeneous catalysis. In this study, we establish air-stable NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl] 2 , as the most reactive Pd(II)–NHC catalysts developed to date. Most crucially, compared with [Pd(NHC)(allyl)Cl] complexes, replacement of the allyl throw-away ligand with chloride allows for a more facile activation step, while effectively preventing the formation of off-cycle [Pd 2 (μ-allyl)(μ-Cl)(NHC) 2 ] products. The utility is demonstrated via broad compatibility with amide cross-coupling, Suzuki cross-coupling, and the direct, late-stage functionalization of pharmaceuticals. Computational studies provide key insight into the NHC–Pd(II) chloro-dimer activation pathway. A facile synthesis of NHC–Pd(II) chloro-dimers in one-pot from NHC salts is reported. Considering the tremendous utility of Pd-catalyzed cross-coupling reactions and the overwhelming success of [Pd(NHC)(allyl)Cl] precatalysts, we believe that NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl] 2 , should be considered as go-to precatalysts of choice in cross-coupling processes.

Cooperative bimetallic catalysis is a fundamental approach in modern synthetic chemistry. We report bimetallic cooperative catalysis for the direct decarbonylative heteroarylation of ubiquitous carboxylic acids via acyl C‐O/C‐H coupling. This novel catalytic system exploits the cooperative action of a copper catalyst and a palladium catalyst in decarbonylation, which enables highly chemoselective synthesis of important heterobiaryl motifs through the coupling of carboxylic acids with heteroarenes in the absence of prefunctionalization or directing groups. This cooperative decarbonylative method uses common carboxylic acids and shows a remarkably broad substrate scope (>70 examples), including late‐stage modification of pharmaceuticals and streamlined synthesis of bioactive agents. Extensive mechanistic and computational studies were conducted to gain insight into the mechanism of the reaction. The key step involves intersection of the two catalytic cycles via transmetallation of the copper–aryl species with the palladium(II) intermediate generated by oxidative addition/decarbonylation.

We report a combined experimental and computational study of the Buchwald–Hartwig cross-coupling of amides by N–C(O) cleavage (transamidation) using well-defined, air- and moisture-stable [Pd(NHC)(allyl)Cl] precatalysts.

Palladium-catalyzed Suzuki-Miyaura cross-coupling or aryl halides is widely employed in the synthesis of many important molecules in synthetic chemistry, including pharmaceuticals, polymers and functional materials. Herein, we disclose the first palladium-catalyzed decarbonylative Suzuki-Miyaura crosscoupling of amides for the synthesis of biaryls through the selective activation of the N-C(O) bond of amides. This new method relies on the precise sequence engineering of the catalytic cycle, wherein decarbonylation occurs prior to the transmetallation step. The reaction is compatible with a wide range of boronic acids and amides, providing valuable biaryls in high yields (>60 examples). DFT studies support a mechanism involving oxidative addition, decarbonylation and transmetallation and provide insight into high N-C(O) bond activation selectivity. Most crucially, the reaction establishes the use of palladium catalysis in the biaryl Suzuki-Miyaura cross-coupling of the amide bond and should enable the design of a wide variety of cross-coupling methods in which palladium rivals the traditional biaryl synthesis from aryl halides and pseudohalides.

Although palladium-catalyzed cross-coupling of aryl halides and reactive pseudohalides has revolutionized the way organic molecules are constructed today across various fields of chemistry, comparatively less progress has been made in...

On the basis of the pyridazinone scaffold and photoinduced electron transfer (PET) mechanism, we designed a smart nitric oxide (NO) probe, PYSNO, with high sensitivity and selectivity. PYSNO exhibited a rapid response to both exogenous and endogenous NO. This probe can also be used in tracking and investigating NO generation in animal tissue. In the myocardial fibrosis model for mice, PYSNO exhibited a powerful imaging property in vivo as a result of unravelling the progressive relationship between the generation of myocardial NO and the occurrence of myocardial fibrosis.

We describe the direct synthesis of organophosphorus compounds from ubiquitous aryl and vinyl carboxylic acids via decarbonylative palladium catalysis. The catalytic system shows excellent scope and tolerates a wide range of functional groups (>50 examples). The utility of this powerful methodology is highlighted in the late-stage derivatization directly exploiting the presence of the prevalent carboxylic acid functional group. DFT studies provided insight into the origin of high bond activation selectivity and P­(O)–H isomerization pathway.