Ru₃(CO)₁₂‐Catalyzed Modular Assembly of Hemilabile Ligands by C−H Activation of Phosphines with Isocyanates

Abstract

Hemilabile ligands have been applied extensively in transition metal catalysis, but preparations of these molecules typically require multistep synthesis.Here, modular assembly of diverse phosphine-amide ligands, including related axially chiral compounds, is first reported through ruthenium-catalyzed CÀ H activation of phosphines with isocyanate directed by phosphorus(III) atoms. High reactivity and regioselectivity can be obtained by using a Ru 3 (CO) 12 catalyst with a mono-N-protected amino acid ligand. This transformation significantly expands the pool of phosphine-amide ligands, some of which have shown excellent efficiency for asymmetric catalysis. More broadly, the discovery constitutes a proof of principle for facile construction of hemilabile ligands directly from the parent monodentate phosphines by CÀ H activation with ideal atom, step and redox economy. Several dinuclear ruthenium complexes were characterized by single-crystal X-ray diffraction analysis revealing the key mechanistic features of this transformation.

Late-Stage Diversification of Phosphines by C–H Activation: A Robust Strategy for Ligand Design and Preparation

“…Beyond triphenylphosphine, substituting one phenyl group with an alkyl group and replacing all three aryl groups with thiophene units also yielded the corresponding silylated products in moderate yields. The developed catalytic system demonstrated notable reactivity not only for aromatic C−H bonds but also for sp 3 C−H bonds, realizing efficient benzylic C−H silylation (Figure 24). The use of substrates with different substituents resulted in high yields for the benzylic C−H silylation products, with selectivity favoring monosilylated outcomes even when bulky groups were present.…”

“…Chem., Int. Ed.202362e202214584 This study introduces a new method for creating hemilabile phosphine-amide ligands, including axially chiral types, through the ruthenium-catalyzed C–H activation of phosphines directed by P­(III) atoms using isocyanates. JiangW.YangX.LinL.YanC.ZhaoY.WangM.ShiZ. Jiang, W. Yang, X. Lin, L. Yan, C. Zhao, Y. Wang, M. Shi, Z.…”

“…Chem., Int. Ed.202362e202214584 This study introduces a new method for creating hemilabile phosphine-amide ligands, including axially chiral types, through the ruthenium-catalyzed C–H activation of phosphines directed by P­(III) atoms using isocyanates.…”

P(III)-Directed Asymmetric C–H Arylation toward Planar Chiral Ferrocenes by Palladium Catalysis

“…Therefore, additional steps are still necessary to convert the resulting products into phosphine ligands. ,,, The use of P­(III) directing groups in catalytic C–H activation presents challenges due to their stronger coordination with metals and higher dissociation energy. Despite these challenges, recent progress made by our group and others has shown promising advancements in catalytic P­(III)-directed C–H activation reactions involving phosphines. However, the asymmetric variant of these reactions still faces difficulties due to strong background reactions and limited availability of prochiral substrates.…”

Access to Amides and Lactams via Pyridotriazole as a Transformable Directing Group

“…Amide and lactam scaffolds are a class of substantial motifs frequently found in pharmaceuticals and naturally occurring molecules like imatinib, lenalidomide, and elmenol H. − A wide range of approaches to constructing such indispensable amide bonds have been developed, ranging from conventional acylation of amines mediated by amide coupling agents , to modern strategies such as catalytic direct amidation , or visible light irradiation. , Among these studies, transition-metal-catalyzed C–H activation stands out as a simpler synthetic route for direct amidation of unactivated C–H bonds. − Many transition-metal-catalyzed C–H functionalization methods require directing groups (DGs), − especially transformable DGs, to enhance the regioselectivity and practicality. − By the DG-assisted C–H activation strategy, selectively installing nitrogen-based functional groups (FGs) into molecules via the direct addition of C–H bonds to unsaturated polar C–N π-bonds represents the most powerful and economical method for rapid amide and lactam synthesis. − We envisioned isocyanates to be particularly useful. As useful carbon synthons in organic synthesis, isocyanates have been extensively implemented in the construction of C–C bond formation for forging amides. − Hence, employing isocyanates as FGs would be a more straightforward approach to the synthesis of amides.…”