Dual Photochemical H-Atom Transfer and Cobalt Catalysis for the Desaturative Synthesis of Phenols from Cyclohexanones

Abstract Phenols are integral aromatic molecules widely encountered in the structure of natural products and routinely utilised for the synthesis of high-value materials. Accessing highly substituted derivatives can often be difficult, especially when their functionalization pattern does not match the intrinsic reactivity leveraged by electrophilic aromatic substitution (SEAr) chemistry. Here, we provide an alternative and mechanistically distinct approach for phenol synthesis using saturated cyclohexanone precursors. This process operates at ambient temperature, under simple purple light irradiation, and features a dual catalytic manifold carrying four sequential H-atom transfer processes

A Desaturative Approach for Aromatic Aldehyde Synthesis via Synergistic Enamine, Photoredox and Cobalt Triple Catalysis

Aromatic aldehydes are fundamental intermediates that are widely utilised for the synthesis of important materials across the broad spectrum of chemical industries. Accessing highly substituted derivatives can often be difficult as their functionalizations are generally performed via electrophilic aromatic substitution, S(E)Ar. Here we provide an alternative and mechanistically distinct approach whereby aromatic aldehydes are assembled from saturated precursors via a desaturative process. This novel strategy harnesses the high‐fidelity of Diels–Alder cycloadditions to quickly construct multi‐substituted cyclohexenecarbaldehyde cores which undergo desaturation via the synergistic interplay of enamine, photoredox and cobalt triple catalysis

A general strategy for the amination of electron-rich and electron-poor heteroaromatics by desaturative catalysis

The introduction of alkylamines onto heteroaromatics is integral to the preparation of high-value molecules. Typical methods rely on heteroaromatic pre-functionalization by halogenation or nitration, followed by metal-catalysed cross-coupling or multi-step manipulation of the nitrogen functionality. This results in often unselective or low-yielding synthetic routes. Here we show an alternative approach in which saturated heterocyclic ketones are used as aryl surrogates for desaturative coupling with amines. The process operates under mild photochemical conditions, is compatible with complex amines and delivers both electron-poor and -rich heteroaromatics that are difficult to access by other methods. As ketones are readily decorated by carbonyl chemistry, this retrosynthetic tactic escapes the rules and limitations of aromatic reactivity and metal-catalysed cross-couplings. Our process uses enamine formation to create the key carbon–nitrogen bond, followed by two rounds of photoredox oxidation and cobalt-catalysed desaturation. The two desaturation steps are distinct, as the cobaloxime first acts as a hydrogen atom abstractor and then an oxidant