Ru(II)-Catalyzed C–H Activation: Amide-Directed 1,4-Addition of the Ortho C–H Bond to Maleimides

Abstract

Maleimide has been used as a selective coupling partner to generate conjugate addition products exclusively. The typical Heck-type oxidative coupling that occurs when alkenes are used is avoided by choosing maleimide as an alkene, which cannot undergo β-hydride elimination due to the unavailability of a syn-periplanar β-hydrogen atom. The amide nitrogen, which is notorious for undergoing tandem reactions to generate spirocyclic or annulation products under cross-coupling conditions, remains innocent in this report. Along with the substrate scope, a robustness screen has been performed to analyze the performance of amide as a directing group in the presence of other directing groups and also to examine the tolerance of the reaction conditions for other frequently encountered functional groups.

Beyond Friedel and Crafts: Directed Alkylation of C−H Bonds in Arenes

“…This reaction can also be performed from the corresponding allylic alcohols in the presence of an additional oxidant under ruthenium or rhodium catalysis [81] and maleimides can be used as alkylating agents. [82] Iridium catalysis was also shown to provide remarkably efficient systems for the branched-selective ortho-alkylation of benzamides with ar ange of alkenes-the formation of branched products is much more challenging to achieve. Indeed, the Bower group showed that monosubstituted alkenes can be efficiently used for the branched-selective ortho-alkylation of aseries of aromatic amides using acationic iridium(I) catalyst modified with an electron-deficient biphosphine ligand with aw ide bite angle [Scheme 17, Eq.…”

C–H Functionalization of Aromatic Amides

“…Prabhu and co‐workers developed an amide‐directed, Ru(II)‐catalyzed ortho‐ alkylation of aromatic amides to prepare 3‐arylsuccinimides (Scheme ) . The reaction was carried out in DCE as solvent with [RuCl 2 ( p ‐cymene)] 2 as catalyst, AgBF 4 as activator, Cu(OAc) 2 ⋅H 2 O as acetate salt and AcOH as protonation source at 100 °C.…”

Alkylation, Annulation, and Alkenylation of Organic Molecules with Maleimides by Transition‐Metal‐Catalyzed C‐H Bond Activation

“…In 2016, Prabhu's group reported ortho alkylation of benzamide derivatives with maleimides catalyzed by the Ru(II) arene complex . When N ‐methylbenzamide ( 18 a ) was treated with N ‐ethylmaleimide ( 19 a ) in the presence of [{RuCl 2 (p‐cymene)} 2 ] (5 mol%), AgBF 4 (20 mol%), Cu(OAc) 2 ⋅ H 2 O (1.5 equiv) and AcOH (10 equiv) at 100 °C in DCE, an ortho alkylated benzamide derivative 20 a was observed in 91% yield (Scheme ).…”