Room-Temperature Cu(II) Radical-Triggered Alkyne C–H Activation

Abstract

A dimeric Cu(II) complex [Cu(II) 2 L 2 (μ 2 -Cl)Cl] (1) built from an asymmetric tridentate ligand (2-(((2aminocyclohexyl)imino)methyl)-4,6-di-tert-butylphenol) and weakly coordinating anions has been synthesized and structurally characterized. In dichloromethane solution, 1 exists in a monomeric [Cu(II)LCl] (1′) (85%)−dimeric (1) (15%) equilibrium, and cyclic voltammetry (CV) and electron paramagnetic resonance (EPR) studies indicate structural stability and redox retention. Addition of phenylacetylene to the CH 2 Cl 2 solution populates 1′ and leads to the formation of a transient radical species. Theoretical studies support this notion and show that the radical initiates an alkyne C−H bond activation process via a fourmembered ring (Cu(II)−O•••H−C alkyne ) intermediate. This unusual C−H activation method is applicable for the efficient synthesis of propargylamines, without additives, within 16 h, at low loadings and in noncoordinating solvents including late-stage functionalization of important bioactive molecules. Single-crystal X-ray diffraction studies, postcatalysis, confirmed the framework's stability and showed that the metal center preserves its oxidation state. The scope and limitations of this unconventional protocol are discussed.

Accessing three-branched high-affinity cereblon ligands for molecular glue and protein degrader design

“…After cleavage of the Boc protecting group in acidic media and subsequent HATU-mediated coupling to JQ1, a well-studied bromodomain inhibitor, 35 BRD4-targeting PROTACs 13a–13d containing different linker shapes were realized. Similar to a JQ1-derivative with two stereogenic centers, 36 diastereomeric differentiability was not evident in the chromatographic and spectroscopic data. For this set of PROTACs, physicochemical properties, and BRD4 degradation were determined (Table 2).…”

Chemical Chartographisis: a contemporary perspective in molecular design and synthesis

“…7). 51 Single crystal structure determination suggests the presence of a dimeric species, with the chlorides acting as bridges in the solid state. However, upon dissolution in DCM, the compound exists in a monomeric [Cu II L7 Cl] (85%), – dimeric (15%) equilibrium and treatment with phenylacetylene populates the monomeric species.…”

Exploring amine-rich supramolecular silver(i) metallogels for autonomous self-healing and as catalysts for a three component coupling reaction

“…A three-component reaction, namely A 3 coupling, of an aldehyde, a terminal acetylene and an amine leading to propargylamines is an atom-and step-economic transformation. [37][38][39][40][41][42] Although gold-and silver-based homogeneous catalysts display outstanding performance, they are expensive and not reusable. 37,38,41 Recently, a few polymer-and/or other functional material-supported copper catalysts have been reported to be heterogeneous and recyclable catalysts for three component coupling.…”