Daniel Zell

N-Acyl Amino Acid Ligands for Ruthenium(II)-Catalyzed meta-C–H tert-Alkylation with Removable Auxiliaries

Acylated amino acid ligands enabled ruthenium(II)-catalyzed C-H functionalizations with excellent levels of meta-selectivity. The outstanding catalytic activity of the ruthenium(II) complexes derived from monoprotected amino acids (MPAA) set the stage for the first ruthenium-catalyzed meta-functionalizations with removable directing groups. Thereby, meta-alkylated anilines could be accessed, which are difficult to prepare by other means of direct aniline functionalizations. The robust nature of the versatile ruthenium(II)-MPAA was reflected by challenging remote C-H transformations with tertiary alkyl halides on aniline derivatives as well as on pyridyl-, pyrimidyl-, and pyrazolyl-substituted arenes. Detailed mechanistic studies provided strong support for an initial reversible C-H ruthenation, followed by a SET-type C-Hal activation through homolytic bond cleavage. Kinetic analyses confirmed this hypothesis through an unusual second-order dependence of the reaction rate on the ruthenium catalyst concentration. Overall, this report highlights the exceptional catalytic activity of ruthenium complexes derived from acylated amino acids, which should prove instrumental for C-H activation chemistry beyond remote functionalization.

Manganese‐Catalyzed Synthesis of cis‐β‐Amino Acid Esters through Organometallic CH Activation of Ketimines

Manganese-catalyzed CH functionalization reactions of ketimines set the stage for the expedient synthesis of cis-β-amino acid esters through site- and regioselective alkene annulations. The organometallic CH activation occurred efficiently with high functional group tolerance, delivering densely functionalized β-amino acid derivatives with ample scope.

Mild C−H/C−C Activation by Z‐Selective Cobalt Catalysis

Cationic cobalt complexes enable unprecedented cobalt-catalyzed C-H/C-C functionalizations with unique selectivity features. The versatile cobalt catalyst proved broadly applicable, enabled efficient C-H/C-C cleavage at room temperature, and delivered Z-alkenes with excellent diastereocontrol.

Single-Component Phosphinous Acid Ruthenium(II) Catalysts for Versatile C−H Activation by Metal–Ligand Cooperation

Well-defined ruthenium(II) phosphinous acid (PA) complexes enabled chemo-, site-, and diastereoselective C-H functionalization of arenes and alkenes with ample scope. The outstanding catalytic activity was reflected by catalyst loadings as low as 0.75 mol %, and the most step-economical access reported to date to angiotensin II receptor antagonist blockbuster drugs. Mechanistic studies indicated a kinetically relevant C-X cleavage by a single-electron transfer (SET)-type elementary process, and provided evidence for a PA-assisted C-H ruthenation step.

Full Selectivity Control in Cobalt(III)‐Catalyzed C−H Alkylations by Switching of the C−H Activation Mechanism

Selectivity control in hydroarylation-based C-H alkylation has been dominated by steric interactions. A conceptually distinct strategy that exploits the programmed switch in the C-H activation mechanism by means of cobalt catalysis is presented, which sets the stage for convenient C-H alkylations with unactivated alkenes. Detailed mechanistic studies provide compelling evidence for a programmable switch in the C-H activation mechanism from a linear-selective ligand-to-ligand hydrogen transfer to a branched-selective base-assisted internal electrophilic-type substitution.

Ruthenium(II)-Catalyzed C-H Oxygenations of Reusable Sulfoximine Benzamides

C-H oxygenations of synthetically meaningful sulfoximine benzamides were accomplished by a versatile ruthenium catalysis regime. The ruthenium(II) catalyst was characterized by excellent mono- and chemoselectivity as well as positional selectivity via facile base-assisted intramolecular electrophilic substitution-type (BIES) C-H activation. The synthetic utility of the approach was reflected by high functional group tolerance and sulfoximine removal in a traceless fashion.

Mild Cobalt(III)-Catalyzed Allylative C-F/C-H Functionalizations at Room Temperature

Sustainable, cobalt-catalyst enabled, synthetically significant C-F/C-H functionalizations were achieved with an ample substrate scope at an ambient temperature of 25 °C, thereby delivering perfluoroallylated heteroarenes. Detailed experimental and computational mechanistic studies on the C-F/C-H functionalizations provided strong support for a facile C-F cleavage.

Asymmetric Iron-Catalyzed C−H Alkylation Enabled by Remote Ligand meta-Substitution

Highly enantioselective iron-catalyzed C-H alkylations by inner-sphere C-H activation were accomplished with ample scope. High levels of enantiocontrol proved viable through a novel ligand design that exploits a remote meta-substitution on N-heterocyclic carbenes within a facile ligand-to-ligand H-transfer C-H cleavage.

Cobalt-catalyzed C–H cyanations: Insights into the reaction mechanism and the role of London dispersion

Carboxylate-assisted cobalt(III)-catalyzed C–H cyanations are highly efficient processes for the synthesis of (hetero)aromatic nitriles. We have now analyzed the cyanation of differently substituted 2-phenylpyridines in detail computationally by density functional theory and also experimentally. Based on our investigations, we propose a plausible reaction mechanism for this transformation that is in line with the experimental observations. Additional calculations, including NCIPLOT, dispersion interaction densities, and local energy decomposition analysis, for the model cyanation of 2-phenylpyridine furthermore highlight that London dispersion is an important factor that enables this challenging C–H transformation. Nonbonding interactions between the Cp* ligand and aromatic and C–H-rich fragments of other ligands at the cobalt center significantly contribute to a stabilization of cobalt intermediates and transition states.