Transition metal-catalyzed intramolecular C-H functionalization

Abstract

Trasition metal-catalyzed C−H functionalization has been extensively investigated to prepare complex molecules as an alternative to the conventional cross-coupling, where pre-functionalized starting materials were required. $Cp^*Ir$ and $Cp^*Rh$ complexes have been utilized in development of C−N and C−C bond construction with chelation-assisted C−H activation. Meanwhile, due to the unstability of metal-nitrenoid and metal-carbenoid, development of efficient reaction using these intermediacy has to be surmounted. In this context, herein I describe the development of C−N and C−C bond forming processes using $Cp^*M$ (M = Rh or Ir) system.

First, I have developed $Cp^*Rh(III)$-catalyzed intramolecular amido transfer as an efficient route to nitrogen-containing macrocycles for the first time. In contrast to the well-studied the conventional C−H insertion approach, which is able to synthesize 5- to 7-membered medium-sized rings, facile generation of rhodacycles and then imido intermediates was readily achieved from ketoximes tethered with azides. While substrates bearing aryl azides underwent a monomeric ring formation in high yields, a dimeric double cyclization took place exclusively with alkyl azide-tethered ketoximes affording up to 36-membered azamacrocyclic products.

Second, a new catalytic procedure for carbon-carbon bond formation has been developed using bidentate LX type ligand based $Cp^*Ir(III)$-carbenoid system. Although metal-carbenoid transfer reaction has been well studied to achieve a wide range of organic transformations, the development of $Cp^*Ir(III)$-carbenoid transfer is still in infancy owing to the lack of solid mechanistic understanding of these putative intermediates. In this study, $Cp^*Ir$-catalyzed carbene transfer reaction was developed using diazo compounds as a carbene precursor with a high turnover number under mild reaction conditions.