Transient Directing Groups for Transformative C–H Activation by Synergistic Metal Catalysis

Abstract

The development of methods for the functionalization of otherwise inert C-H bonds is one of the major foci in molecular syntheses. Recent advances have significantly improved the arsenal of synthetic chemistry, enabling the use of less functionalized starting materials, a reduction of energy consumption, and a minimization of waste production. Despite undisputable progress, the main challenge associated with synthetically meaningful C-H activations is achieving positional selectivity. Thus far, the most common approach to address site selectivity in transition-metal-catalyzed intermolecular transformations is constituted by chelation assistance through directing groups. The installation and removal of these directing groups adds additional steps, compromising the step-economical nature of the overall C-H activation strategy. In contrast, here we discuss the emergence of transient directing group approaches through the in situ installation and deconstruction of a Lewis-basic entity with the aid of co-catalytic additives for selective C-H functionalizations.

Thiocarbonyl-enabled ferrocene C–H nitrogenation by cobalt(III) catalysis: thermal and mechanochemical

“…C–H activation has surfaced as a transformative tool in molecular sciences [1–9]. While major advances have been accomplished with precious 4d transition metals, recent focus has shifted towards more sustainable base metals [10–17], with considerable progress by earth-abundant cobalt catalysts [18–22].…”

Mn‐Catalyzed Dehydrocyanative Transannulation of Heteroarenes and Propargyl Carbonates through C−H Activation: Beyond the Permanent Directing Effects of Pyridines/Pyrimidines

“…[1] In this regime,adirecting group (DG) is almost indispensable to ensure high reactivity and selectivity. [3] Very recently,t hese DGs have been shown to undergo post-coupling migration in af ew reports. Although pyridines/pyrimidines can occasionally become removable after the catalytic transformations,t heir removal amounts to reduced atom-economy.…”

“…Thus,the pyridine directing group acts as aC 4s ynthon in this dehydocyanative coupling.S olvent studies returned MTBE as the optimal medium (entries [1][2][3][4][5]. Ar eaction occurred with MnBr(CO) 5 as the catalyst in the presence of NaOAc, affording the desired transannulation product 3aa in low yield (entry 1).…”

Late‐Stage Diversification through Manganese‐Catalyzed C−H Activation: Access to Acyclic, Hybrid, and Stapled Peptides

“…[2] Thus far, peptide assembly has largely relied on classical approaches,such as diastereoselective ex-chiral-pool syntheses. [4,5] Despite tremendous advances,t his approach inherently requires precious palladium catalysts and substrate prefunctionalization, which leads to undesired byproduct formation and lengthy reaction sequences.Asignificantly more atom-and step-economic strategy is the direct activation of otherwise unreactive C À H bonds, [6] with recent transformative applications towards peptide modification. [4,5] Despite tremendous advances,t his approach inherently requires precious palladium catalysts and substrate prefunctionalization, which leads to undesired byproduct formation and lengthy reaction sequences.Asignificantly more atom-and step-economic strategy is the direct activation of otherwise unreactive C À H bonds, [6] with recent transformative applications towards peptide modification.…”