A tautomeric ligand enables directed C‒H hydroxylation with molecular oxygen

Abstract

Hydroxylation of aryl carbon–hydrogen bonds with transition metal catalysts has proven challenging when oxygen is used as the oxidant. Here, we report a palladium complex bearing a bidentate pyridine/pyridone ligand that efficiently catalyzes this reaction at ring positions adjacent to carboxylic acids. Infrared, x-ray, and computational analysis support a possible role of ligand tautomerization from mono-anionic (L,X) to neutral (L,L) coordination in the catalytic cycle of aerobic carbon–hydrogen hydroxylation reaction. The conventional site selectivity dictated by heterocycles is overturned by this catalyst, thus allowing late-stage modification of compounds of pharmaceutical interest at previously inaccessible sites.

Catalytic synthesis of phenols with nitrous oxide

“…To orchestrate this reductive process, we focused our attention on Ni and its demonstrated ability to manoeuvre between different oxidation states through single-electron transfer 30 – 32 . Here we demonstrate that a mechanistically guided approach for the activation of N 2 O with organometallic complexes results in the development of a mild and selective catalytic synthesis of high-value phenols from aryl halides using N 2 O as an electrophilic O source 33 . The mild conditions (25 °C and 1.5–2 atm) allow the accommodation of a variety of functional groups, including base-sensitive moieties, thus providing an orthogonal strategy to the current technologies (Fig.…”

TEMPO-mediated late stage photochemical hydroxylation of biaryl sulfonium salts

“…14 Most recently, Yu and co-workers even managed the benzoic acid directed Pd-catalyzed ortho hydroxylation of aromatic C–H bonds (eqn (3)). 15 Moreover, they impressively utilized molecular oxygen as both the terminal oxidant and the hydroxyl source. Of course, this strategy requires a specific directing group.…”

Ru‐Catalyzed C−H Hydroxylation of Tyrosine‐Containing Di‐ and Tripeptides toward the Assembly of L‐DOPA Derivatives

“…[9] More recently, as part of their studies on the Pd-catalyzed orthohydroxylation of benzoic acids, Yu and co-workers disclosed the hydroxylation of a Tyr derivative in a remote position featuring a carboxylic acid as a weak DG. [10] Furthermore, the last years have witnessed the upsurge of a sheer number of biocatalytic techniques to perform CÀ H oxidation reactions in intricate scaffolds including amino acids. [11] However, the challenging site-selective CÀ H hydroxylation of tyrosine (Tyr) compounds upon metal catalysis remains elusive.…”