Rhodium(i)-catalyzed cascade C(sp2)-H bond alkylation - amidation of anilines: phosphorus as traceless directing group

Chem Sci. 2023 Aug 1;14(34):9055-9062. doi: 10.1039/d3sc02992a. eCollection 2023 Aug 30.

Abstract

We introduce a versatile Rh(i)-catalyzed cascade reaction, combining C(sp2)-H bond functionalization and amidation between N-arylphosphanamines and acrylates. This innovative approach enables the rapid synthesis of dihydroquinolinone scaffolds, a common heterocycle found in various pharmaceuticals. Notably, the presence of the phosphorus atom facilitates the aniline ortho-C(sp2)-H bond activation prior to N-P bond hydrolysis, streamlining one-pot intramolecular amidation. Moreover, we demonstrate the applicability of this reaction by synthesizing an antipsychotic drug. Detailed mechanistic investigations revealed the involvement of a Rh-H intermediate, with substrate inhibition through catalyst saturation.