C(sp²)–H Activation with Bis(silylene)pyridine Cobalt(III) Complexes: Catalytic Hydrogen Isotope Exchange of Sterically Hindered C–H Bonds

Abstract

The bis­(silylene)­pyridine cobalt­(III) dihydride boryl, trans-[ ptol SiNSi]­Co­(H)2BPin ( ptol SiNSi = 2,6-[EtNSi­(NtBu)2CAr]2 C5H3N, where ptol = 4-MeC6H4, and Pin = pinacolato) has been used as a precatalyst for the hydrogen isotope exchange (HIE) of arenes and heteroarenes using benzene-d 6 as the deuterium source. Use of D2 as the source of the isotope produced modest levels of deuterium incorporation, and stoichiometric studies established modification of the pincer ligand through irreversible addition of H2 across the silylene leading to catalyst deactivation. High levels of deuterium incorporation were observed with benzene-d 6 as the isotope source and enabled low (0.5–5 mol %) loadings of the cobalt precursor. The resulting high activity for C–H activation resulted in deuterium incorporation at sterically encumbered sites previously inaccessible with first-row metal HIE catalysts. The cobalt-catalyzed method was also compatible with aryl halides, demonstrating a kinetic preference for chemoselective C­(sp2)–H activation over C­(sp2)–X (X = Cl, Br) bonds. Monitoring the catalytic reaction by NMR spectroscopy established cobalt­(III) resting states at both low and high conversions of the substrate, and the overall performance was inhibited by the addition of HBPin. Studies on precatalyst activation with cis-[ ptol SiNSi]­Co­(Bf)2H and cis-[ ptol SiNSi]­Co­(H)2Bf (where Bf = 2-benzofuranyl) support the intermediacy of bis­(hydride)­aryl cobalt intermediates as opposed to bis­(aryl)­hydride cobalt complexes in the catalytic HIE method. Mechanistic insights resulted in an improved protocol using [ ptol SiNSi]­Co­(H)3·NaBHEt3 as the precatalyst, ultimately translating onto higher levels of isotopic incorporation.

Remote Site-Selective C(sp3)–H Monodeuteration of Unactivated Alkenes via Chain-Walking Strategy

“…Transition-metal-catalyzed hydrogen isotope exchange (HIE) provides efficient methodologies for the incorporation of deuterium atoms into small molecules, but it is challenging to control the quantity and precise site of deuterium atoms . Notably, an excess of deuterium reagent is required for this approach to guarantee a high level of deuterium incorporation in a given molecule …”

Nondirected Pd-Catalyzed C–H Perdeuteration and meta-Selective Alkenylation of Arenes Enabled by Pyrazolopyridone Ligands

“…Nevertheless, the C–H activation of these challenging positions would enable Pd-catalyzed homogeneous sp 2 C–H perdeuteration for the preparation of perdeuterated drug molecules that are key to drug discovery . Therefore, to complement currently available homogeneous catalytic protocols, , mild and functional-group-compatible methods using readily available ligands and deuterium sources would be highly desirable . In addition, selective alkenylation at the less-electron-rich positions over the conventionally more reactive electron-rich positions of arenes would offer the possibility to perform regiodivergent alkenylation .…”

Hydrogenation of Olefins Catalyzed by a Cobalt(I) Hydride Complex with N‐Heterocyclic Silylene

“…[15b,c] With the development of new NHSi ligands, bis(silylene)cobalt complexes have been found application in several catalytic transformations including [2 + 2 + 2] cycloaddition of phenylacetylene, [16] borylation of arenes, and hydrogen isotope exchange of arenes and heteroarenes. [17] To our knowledge, hydrogenation of olefins catalyzed by cobalt complexes with NHSis has remained unknown. Herein, we report the results of highly chemo-selective hydrogenation of alkenes by a structurally well-defined Co(I) complex with a strong electron-donating NHSi ligand.…”

“…found that a bis( N ‐heterocyclic silylene)xanthene nickel(0) complex is an efficient precatalyst for hydrogenation of olefins, in which the nickel‐silylene cooperation is essential in the catalytic process [15b,c] . With the development of new NHSi ligands, bis(silylene)cobalt complexes have been found application in several catalytic transformations including [2+2+2] cycloaddition of phenylacetylene, [16] borylation of arenes, and hydrogen isotope exchange of arenes and heteroarenes [17] . To our knowledge, hydrogenation of olefins catalyzed by cobalt complexes with NHSis has remained unknown.…”