Experimental and theoretical studies of the rhodium(i)-catalysed C–H oxidative alkenylation/cyclization of N-(2-(methylthio)phenyl)benzamides with maleimides?

Organic Chemistry Frontiers Pub Date: 2023-02-13 DOI: 10.1039/D3QO00023K

Abstract

The rhodium(I)-catalysed reaction of aromatic amides that contain a 2-(methylthio)aniline directing group with maleimides gives isoindolone spirosuccinimides as products under aerobic, metal oxidant-free, and solvent-free conditions. In sharp contrast to our previous study on the C–H alkylation of aromatic amides in which an 8-aminoquinoline directing group was used, the use of a (2-methylthio)aniline directing group resulted in C–H oxidative alkenylation/cyclization. The maleimide has dual functions, i.e., serving as both a coupling partner and a hydrogen acceptor. Several possible reaction paths were examined by density functional theory (DFT) calculations to clarify the mechanism responsible for the formation of the isoindolone spirosuccinimide products. The results of an in-depth computational study indicate that the reaction proceeds via the following main steps: (I) oxidative addition of the ortho C–H bond and the migratory insertion of the maleimide, (II) the insertion of a second molecule of maleimide into a Rh–C bond in a rhodacycle with the formation of a C–C bond and subsequent ligand–ligand hydrogen transfer (LLHT), (III) C–N bond formation between the amide and the maleimide, and (IV) PivOH protonation. The use of an energetic span model along with the determination of the kinetic isotopic effect showed that the determining transition state step for the reaction is the oxidative addition/migratory insertion step.

Graphical abstract: Experimental and theoretical studies of the rhodium(i)-catalysed C–H oxidative alkenylation/cyclization of N-(2-(methylthio)phenyl)benzamides with maleimides
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