No abstract

The impact of O2 on olefin metathesis promoted by Ru-NHC and Ru-CAAC catalysts is examined (NHC = N-heterocyclic carbene; CAAC = cyclic alkyl amino carbene). An atmosphere of 8% O2 in Ar is found to decrease turnover numbers by ca. 15–95% in ring-closing metathesis, including macrocyclization reactions. All H2IMes catalysts studied, irrespective of their ease of initiation, exhibit broadly similar O2-sensitivity, within the middle of this range. Much greater disparities in performance emerge for the CAAC catalysts, which exhibit an unexpected correlation between reactivity and robustness. Fast-initiating CAAC catalysts show greatest resistance to O2 of all systems studied. Mechanistic studies with the second-generation Grubbs catalyst RuCl2(H2IMes)­(PCy3)­(=CHPh), which contains the useful PCy3 and benzylidene reporter groups, suggest that [2 + 2] cycloaddition of O2 dominates over the reported attack of O2 at the benzylidene ligand. At catalyst concentrations compatible with NMR analysis (20 mM Ru), bimolecular coupling of Ru-4 is also a significant contributor to decomposition.

Many commercial drugs, as well as upcoming pharmaceutically active compounds in the pipeline, display aliphatic carboxylic acids or derivatives thereof as key structural entities. Synthetic methods for rapidly accessing isotopologues of such compounds are highly relevant for undertaking critical pharmacological studies. In this paper, we disclose a direct synthetic route allowing for full carbon isotope replacement via a nickel-mediated alkoxycarbonylation. Employing a nickelII pincer complex ([(N2N)­Ni–Cl]) in combination with carbon-13 labeled CO, alkyl iodide, sodium methoxide, photocatalyst, and blue LED light, it was possible to generate the corresponding isotopically labeled aliphatic carboxylates in good yields. Furthermore, the developed methodology was applied to the carbon isotope substitution of several pharmaceutically active compounds, whereby complete carbon-13 labeling was successfully accomplished. It was initially proposed that the carboxylation step would proceed via the in situ formation of a nickellacarboxylate, generated by CO insertion into the Ni–alkoxide bond. However, preliminary mechanistic investigations suggest an alternative pathway involving attack of an open shell species generated from the alkyl halide to a metal ligated CO to generate an acyl NiIII species. Subsequent reductive elimination involving the alkoxide eventually leads to carboxylate formation. An excess of the alkoxide was essential for obtaining a high yield of the product. In general, the presented methodology provides a simple and convenient setup for the synthesis and carbon isotope labeling of aliphatic carboxylates, while providing new insights about the reactivity of the N2N nickel pincer complex applied.

Catalyst encapsulation is examined as a means of increasing the productivity of olefin metathesis catalysts. Commercially available, cationic ruthenium metathesis catalysts were incorporated into a supramolecular resorcin[4]arene capsule. Encapsulation increased catalyst stability in water‐saturated toluene, delivering higher metathesis yields than the parent, non‐encapsulated Hoveyda catalyst in the same reaction medium.

Herein we disclose the synthesis of sterically encumbered dialkylnickel(II) complexes bearing 2,9-dimethyl-1,10phenanthroline ligands. A comparison with their unsubstituted analogues by both X-ray crystallography and theoretical calculations revealed significant distortions in their molecular structures. Eyring plots along with stoichiometric and photoexcitation studies revealed that sterically encumbered dialkylnickel(II) complexes enable facile C(sp 3 )−C(sp 3 ) reductive elimination, thus offering an improved understanding of Ni catalysis.