Easy access to drug building-blocks through benzylic C–H functionalization of phenolic ethers by photoredox catalysis

Abstract

A visible light-mediated photocatalyzed C-C-bond forming method for the benzylic C-H functionalization of phenolether containing synthetic building blocks based on a radical-cation/deprotonation strategy is reported. This method allows the mild,...

Photocatalytic Late-Stage C–H Functionalization

“…This unexpected outcome could be tentatively ascribed to S N 1-type attack onto photochemically generated radical cations (cf. ref 103).…”

“…Furthermore, its β-position modification remains scarcely precedented. The selective single-electron oxidation of the indole system, followed by deprotonation to generate the β-carbon radical, controlled the exquisite selectivity. Other potentially modifiable amino acids, such as methionine (in tetrapeptide), phenylalanine (in tetrapeptide and cyclic peptide), and threonine (in cyclic peptide), remained untouched.…”

“…N-heterocyclic carbenes (NHCs), in addition to their rich and long-standing history of use as umpolung organocatalysts, , have been recently recognized as species capable of stabilizing unpaired electron species and tuning the redox potentials of substrates. , Studer and co-workers devised a dual catalytic manifold toward the late-stage benzylic C–H acylation (Scheme B) . Electron-rich benzylic substrates ( 110.4 ) can undergo single-electron oxidation from the photoexcited 4CzIPN , followed by immediate deprotonation to deliver benzylic radicals 110.12 . In the organocatalytic branch, acyl fluorides 110.5 undergo nucleophilic attack from the free NHC species, and generate an acyl-NHC adduct 110.8 .…”

Transition-metal-catalyzed C–H bond alkylation using olefins: recent advances and mechanistic aspects

“…Recently in 2021, the Mancheno group reported visible light induced benzylic C–H alkylation of phenolether containing synthetic building blocks using an Ir-based photocatalyst with the dCF 3 bpy ligand (Scheme 191). 296 The reaction proceeds through the generation of benzylic radicals 191f via oxidation of 190d ( cf. 190 ) under light excitation of the photoredox catalyst followed by deprotonation of 191e .…”

Direct Access to Unnatural Cyclobutane α-Amino Acids through Visible Light Catalyzed [2+2]-Cycloaddition

“…Indeed, only scarce examples involving formal [2+2]-cycloaddition methodologies have been described, which rely on thermal 26 or Albased Lewis acid promoters. 27,28 Inspired by earlier works on energy transfer (EnT) photocatalysis 46 and our previous contribution to photocatalyzed radical additions toward unnatural amino acids, 42,47 we envisioned an unprecedented method for the functionalization of α,β-dehydroamino acids using a photocatalytic, visible light mediated [2+2]-cycloaddition. Hence, it provides ready access to a variety of cyclobutane 2-substituted α-amino acids while allowing for high selectivity and functional group (FG) tolerance (Scheme 1c).…”