El Diario de Pontevedra : periódico liberal: Ano XXVII Número 7742 - 1910 marzo 1

Copper­(II) aryl species are proposed key intermediates in Cu-catalyzed cross-coupling reactions. Novel three-coordinate copper­(II) aryls [Cu^II]-C₆F₅ supported by ancillary β-diketiminate ligands form in reactions between copper­(II) alkoxides [Cu^II]-O^<i>t</i>Bu and B­(C₆F₅)₃. Crystallographic, spectroscopic, and DFT studies reveal geometric and electronic structures of these Cu­(II) organometallic complexes. Reaction of [Cu^II]-C₆F₅ with the free radical NO_(g) results in C-N bond formation to give [Cu]­(η²-ONC₆F₅). Remarkably, addition of the phenolate anion PhO^– to [Cu^II]-C₆F₅ directly affords diaryl ether PhO-C₆F₅ with concomitant generation of the copper­(I) species [Cu^I]­(solvent) and {[Cu^I]-C₆F₅}⁻. Experimental and computational analysis supports redox disproportionation between [Cu^II]-C₆F₅ and {[Cu^II]­(C₆F₅)­(OPh)}⁻ to give {[Cu^I]-C₆F₅}⁻ and [Cu^III]­(C₆F₅)­(OPh) unstable toward reductive elimination to [Cu^I]­(solvent) and PhO-C₆F₅

Evaluation of Difluoromethyl Ketones as Agonists of the γ‑Aminobutyric Acid Type B (GABA_B) Receptor

The design, synthesis, biological evaluation, and in vivo studies of difluoromethyl ketones as GABA_B agonists that are not structurally analogous to known GABA_B agonists, such as baclofen or 3-aminopropyl phosphinic acid, are presented. The difluoromethyl ketones were assembled in three synthetic steps using a trifluoroacetate-release aldol reaction. Following evaluation at clinically relevant GABA receptors, we have identified a difluoromethyl ketone that is a potent GABA_B agonist, obtained its X-ray structure, and presented preliminary in vivo data in alcohol-preferring mice. The behavioral studies in mice demonstrated that this compound tended to reduce the acoustic startle response, which is consistent with an anxiolytic profile. Structure–activity investigations determined that replacing the fluorines of the difluoromethyl ketone with hydrogens resulted in an inactive analogue. Resolution of the individual enantiomers of the difluoromethyl ketone provided a compound with full biological activity at concentrations less than an order of magnitude greater than the pharmaceutical, baclofen

Evaluation of Difluoromethyl Ketones as Agonists of the γ‑Aminobutyric Acid Type B (GABA_B) Receptor

The design, synthesis, biological evaluation, and in vivo studies of difluoromethyl ketones as GABA_B agonists that are not structurally analogous to known GABA_B agonists, such as baclofen or 3-aminopropyl phosphinic acid, are presented. The difluoromethyl ketones were assembled in three synthetic steps using a trifluoroacetate-release aldol reaction. Following evaluation at clinically relevant GABA receptors, we have identified a difluoromethyl ketone that is a potent GABA_B agonist, obtained its X-ray structure, and presented preliminary in vivo data in alcohol-preferring mice. The behavioral studies in mice demonstrated that this compound tended to reduce the acoustic startle response, which is consistent with an anxiolytic profile. Structure–activity investigations determined that replacing the fluorines of the difluoromethyl ketone with hydrogens resulted in an inactive analogue. Resolution of the individual enantiomers of the difluoromethyl ketone provided a compound with full biological activity at concentrations less than an order of magnitude greater than the pharmaceutical, baclofen