Rhodium(III)-catalyzed annulation for the construction of indolizinone and quinolizinone scaffolds through C(sp2)-H activation

This research focuses on several explorations of the construction of indolizinone and quinolizinone scaffolds through rhodium(III)-catalyzed C(sp2)-H activation followed by annulation with alkynes. Based on the understanding of transition metal-catalyzed C-H activation, as well as knowing the significance of indolizinone and quinolizinone scaffolds, the possibility of combining them is investigated. By different designs of substrate structures, indolizinone and quinolizinone scaffolds could be synthesized in different ways.

Part 1 presents an intramolecular annulation of alkyne-tethered benzamides through rhodium(III)-catalyzed C-H activation for the synthesis of indolizinone and quinolizinone scaffolds, providing a flexible and efficient synthesis of rosettacin and tetrahydropalmatine.

Part 2 depicts a chemoselective rhodium(III)-catalyzed cascade annulation for the construction of indolizinone and quinolizinone scaffolds. Diversification of peptidomimetics and oligopeptides is achieved in a rapid and step-economical manner through the combination of Ugi reaction and microwave-assisted rhodium(III)-catalyzed intramolecular annulation via C(sp2)-H activation.

Part 3 introduces an intramolecular cascade annulation of O-substituted N-hydroxybenzamides or N-hydroxyacrylamides for the construction of indolizinone scaffolds without adding an external oxidant. Through rhodium(III)-catalyzed sequential C(sp2)-H activation and C(sp3)-H amination, diverse indolizinones are obtained under mild conditions by using an internal oxidant.

Part 4 shows an intermolecular cascade annulation of 2-acetylenic aldehydes or ketones with O-substituted N-hydroxybenzamides or N-hydroxyacrylamides for the formation of isoquinolone and indolizinone scaffolds employing an internal oxidant. The rhodium(III)-catalyzed intermolecular annulation avoids the employment of a stoichiometric external oxidant, harsh conditions and lengthy synthetic operations.