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

Chemical Science Pub Date: 2023-08-01 DOI: 10.1039/D3SC02992A

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.

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