Mild Pd-Catalyzed Aminocarbonylation of (Hetero)Aryl Bromides with a Palladacycle Precatalyst

A palladacyclic precatalyst is employed to cleanly generate a highly active XantPhos-ligated Pd-catalyst. Its use in low temperature aminocarbonylations of (hetero)aryl bromides provides access to a range of challenging products in good to excellent yields with low catalyst loading and only a slight excess of CO. Some products are unattainable by traditional carbonylative coupling.National Institutes of Health (U.S.) (Award GM46059)Danish National Research Foundation (Grant DNRF59)Villum FoundationDanish Council for Independent Researc

Chronic T cell receptor stimulation unmasks NK receptor signaling in peripheral T cell lymphomas via epigenetic reprogramming.

Peripheral T cell lymphomas (PTCLs) represent a significant unmet medical need with dismal clinical outcomes. The T cell receptor (TCR) is emerging as a key driver of T lymphocyte transformation. However, the role of chronic TCR activation in lymphomagenesis and in lymphoma cell survival is still poorly understood. Using a mouse model, we report that chronic TCR stimulation drove T cell lymphomagenesis, whereas TCR signaling did not contribute to PTCL survival. The combination of kinome, transcriptome, and epigenome analyses of mouse PTCLs revealed a NK cell-like reprogramming of PTCL cells with expression of NK receptors (NKRs) and downstream signaling molecules such as Tyrobp and SYK. Activating NKRs were functional in PTCLs and dependent on SYK activity. In vivo blockade of NKR signaling prolonged mouse survival, demonstrating the addiction of PTCLs to NKRs and downstream SYK/mTOR activity for their survival. We studied a large collection of human primary samples and identified several PTCLs recapitulating the phenotype described in this model by their expression of SYK and the NKR, suggesting a similar mechanism of lymphomagenesis and establishing a rationale for clinical studies targeting such molecules

Synthesis, characterization, and reactivity of N-heterocyclic carbene palladium(II) hydroxide dimers

Palladium hydroxide dimers were prepared by reactions of CsOH with monomeric [Pd(NHC)(eta(3)-allyl)Cl] starting materials. The dimers represent species proposed as intermediates in important cross-coupling reactions. These complexes were tested for their catalytic activity in Suzuki-Miyaura coupling and Buchwald-Hartwig aryl amination. The hydroxide complexes were susceptible to hydrogenolysis on exposure to H-2 gas. Following H2O elimination and beta-hydride elimination of an additional cinnamyl ligand, a Pd(0) species is formed which can react with other available ligands

Synthesis, Characterization, and Reactivity of N-Heterocyclic Carbene Palladium(II) Hydroxide Dimers

Palladium hydroxide dimers were prepared by reactions of CsOH with monomeric [Pd(NHC)(eta(3)-allyl)Cl] starting materials. The dimers represent species proposed as intermediates in important cross-coupling reactions. These complexes were tested for their catalytic activity in Suzuki-Miyaura coupling and Buchwald-Hartwig aryl amination. The hydroxide complexes were susceptible to hydrogenolysis on exposure to H-2 gas. Following H2O elimination and beta-hydride elimination of an additional cinnamyl ligand, a Pd(0) species is formed which can react with other available ligands.</p

Synthesis, Characterization, and Reactivity of N-Heterocyclic Carbene Palladium(II) Hydroxide Dimers

Palladium hydroxide dimers were prepared by reactions of CsOH with monomeric [Pd(NHC)(η3-allyl)Cl] starting materials. The dimers represent species proposed as intermediates in important cross-coupling reactions. These complexes were tested for their catalytic activity in Suzuki–Miyaura coupling and Buchwald–Hartwig aryl amination. The hydroxide complexes were susceptible to hydrogenolysis on exposure to H2 gas. Following H2O elimination and β-hydride elimination of an additional cinnamyl ligand, a Pd(0) species is formed which can react with other available ligands

Synthesis, Characterization, and Reactivity of N-Heterocyclic Carbene Palladium(II) Hydroxide Dimers

Palladium hydroxide dimers were prepared by reactions of CsOH with monomeric [Pd(NHC)(η3-allyl)Cl] starting materials. The dimers represent species proposed as intermediates in important cross-coupling reactions. These complexes were tested for their catalytic activity in Suzuki–Miyaura coupling and Buchwald–Hartwig aryl amination. The hydroxide complexes were susceptible to hydrogenolysis on exposure to H2 gas. Following H2O elimination and β-hydride elimination of an additional cinnamyl ligand, a Pd(0) species is formed which can react with other available ligands

Synthesis, Characterization, and Reactivity of N-Heterocyclic Carbene Palladium(II) Hydroxide Dimers

Palladium hydroxide dimers were prepared by reactions of CsOH with monomeric [Pd(NHC)(η3-allyl)Cl] starting materials. The dimers represent species proposed as intermediates in important cross-coupling reactions. These complexes were tested for their catalytic activity in Suzuki–Miyaura coupling and Buchwald–Hartwig aryl amination. The hydroxide complexes were susceptible to hydrogenolysis on exposure to H2 gas. Following H2O elimination and β-hydride elimination of an additional cinnamyl ligand, a Pd(0) species is formed which can react with other available ligands

Synthesis, Characterization, and Reactivity of N-Heterocyclic Carbene Palladium(II) Hydroxide Dimers

Palladium hydroxide dimers were prepared by reactions of CsOH with monomeric [Pd(NHC)(η3-allyl)Cl] starting materials. The dimers represent species proposed as intermediates in important cross-coupling reactions. These complexes were tested for their catalytic activity in Suzuki–Miyaura coupling and Buchwald–Hartwig aryl amination. The hydroxide complexes were susceptible to hydrogenolysis on exposure to H2 gas. Following H2O elimination and β-hydride elimination of an additional cinnamyl ligand, a Pd(0) species is formed which can react with other available ligands

Synthesis, Characterization, and Reactivity of N-Heterocyclic Carbene Palladium(II) Hydroxide Dimers

Palladium hydroxide dimers were prepared by reactions of CsOH with monomeric [Pd(NHC)(η3-allyl)Cl] starting materials. The dimers represent species proposed as intermediates in important cross-coupling reactions. These complexes were tested for their catalytic activity in Suzuki–Miyaura coupling and Buchwald–Hartwig aryl amination. The hydroxide complexes were susceptible to hydrogenolysis on exposure to H2 gas. Following H2O elimination and β-hydride elimination of an additional cinnamyl ligand, a Pd(0) species is formed which can react with other available ligands