Steering Site‐Selectivity in Transition Metal‐Catalyzed C−H Bond Functionalization: the Challenge of Benzanilides

Abstract

SelectiveC ÀHb ond functionalization catalyzed by metal complexes have completely revolutionized the wayi n which chemical synthesis is conceived nowadays. Typically, the reactivityo fat ransitionm etal catalyst is the key to control the site-, regio-and/or stereo-selectivity of aC ÀHb ond functionalization. Of particulari nterests are molecules that contain multiple CÀHb onds prone to undergo CÀHb ond activations with very similar bond dissociation energies at different positions. This is the case of benzanilides, relevant chemical motifs that are found in many useful fine chemicals, in which two CÀHs ites are present in chemically different aromatic fragments. In the last years, it has been found that depending on the metal catalyst and the reaction conditions, the amide motif might behave as ad irecting group towardst he metal-catalyzed CÀHb ond activation in the benzamide site or in the anilides ite. The impact and the consequences of such subtle control of site-selectivity are herein reviewed with important applicationsi ncarboncarbon and carbon-heteroatomb ond forming processes. The mechanisms unraveling these unique transformations are discussed in order to provide ab etter understanding for future developmentsi nt he field of site-selective CÀHb ond functionalization with transition metal catalysts.

Ruthenium-Catalyzed C(sp2)–H Bond Bisallylation with Imidazopyridines as Directing Groups

“…On the other hand, employment of VCC 4 led to formation of bisallylated products 8b and 9b in 56 and 89% yields, respectively. Inspired by the weakly coordinating directing groups for C–H activation, acetophenone and N -( tert -butyl)­benzamide were chosen to react with VCP 2a , which unfortunately failed to give the corresponding products.…”

Palladium‐Catalyzed Annulation of Arylbenzamides with Diaryliodonium Salts

“…As comprehensively summarized by Gramage‐Doria in 2020, controlling chemical reactivity at specific positions of N ‐phenylbenzamides represents the research of interest [6] . In this respect, phenylbenzamide contains a single amide motif linking two aromatic units, thus resulted in diverse reactivity.…”

Ruthenium-catalyzed C–H bond functionalization in cascade and one-pot transformations

“…They correspond to an association of either two catalytic cycles, or one catalytic cycle and one stoichiometric reaction (Figure 1). The mechanistic aspects [28] and catalytic cycles, which have been previously presented in articles and reviews on ruthenium-catalyzed C-H bond functionalizations [29][30][31][32][33][34][35][36][37][38][39][40][41], are not described in detail, but quoted when necessary for the understanding of the sequence. Bis-functionalization reactions represented by ortho, ortho'-C-C bond formation such as double arylation or double alkenylation for instance, are not considered since the same catalytic cycle operates twice [42].…”