Aminoborane σ Complexes: Significance of Hydride Co-ligands in Dynamic Processes and Dehydrogenative Borylene Formation

Systems of the type [(<i>p</i>-cym)­Ru­(PR₃)­(H)­(H₂BN^<i>i</i>Pr₂)]⁺ (R = Cy, Ph) can be synthesized from (<i>p</i>-cym)­Ru­(PR₃)­Cl₂ and H₂BN^<i>i</i>Pr₂/Na­[BAr^<i>f</i>₄] and are best formulated as (hydrido)ruthenium κ¹-aminoborane complexes. VT-NMR measurements have been used to probe the σ-bond metathesis process leading to Ru–H/H–B exchange, yielding an activation barrier of Δ<i>G</i>^⧧ = 7.5 kcal mol^–1 at 161 K. Moreover, in contrast to the case for related non-hydride-containing systems, reactivity toward alkenes constitutes a viable route to a metal borylene complex via sacrificial hydrogenation

Aminoborane σ Complexes: Significance of Hydride Co-ligands in Dynamic Processes and Dehydrogenative Borylene Formation

Systems of the type [(<i>p</i>-cym)­Ru­(PR₃)­(H)­(H₂BN^<i>i</i>Pr₂)]⁺ (R = Cy, Ph) can be synthesized from (<i>p</i>-cym)­Ru­(PR₃)­Cl₂ and H₂BN^<i>i</i>Pr₂/Na­[BAr^<i>f</i>₄] and are best formulated as (hydrido)ruthenium κ¹-aminoborane complexes. VT-NMR measurements have been used to probe the σ-bond metathesis process leading to Ru–H/H–B exchange, yielding an activation barrier of Δ<i>G</i>^⧧ = 7.5 kcal mol^–1 at 161 K. Moreover, in contrast to the case for related non-hydride-containing systems, reactivity toward alkenes constitutes a viable route to a metal borylene complex via sacrificial hydrogenation

Optimization of Novel Aza-benzimidazolone mGluR2 PAMs with Respect to LLE and PK Properties and Mitigation of CYP TDI

Investigation of a novel amino-aza-benzimidazolone structural class of positive allosteric modulators (PAMs) of metabotropic glutamate receptor 2 (mGluR2) identified [2.2.2]-bicyclic amine <b>12</b> as an intriguing lead structure due to its promising physicochemical properties and lipophilic ligand efficiency (LLE). Further optimization led to chiral amide <b>18</b>, which exhibited strong <i>in vitro</i> activity and attractive pharmacokinetic (PK) properties. Hypothesis-driven target design identified compound <b>21</b> as a potent, highly selective, orally bioavailable mGluR2 PAM, which addressed a CYP time-dependent inhibition (TDI) liability of <b>18</b>, while maintaining excellent drug-like properties with robust <i>in vivo</i> activity in a clinically validated model of antipsychotic potential