Selective functionalization of ubiquitous unactivated C–H bonds is a continuous quest for synthetic organic chemists. In addition to transition metal catalysis, which typically operates under a two-electron manifold, a recent renaissance in the radical approach relying on the hydrogen atom transfer (HAT) process has led to tremendous growth in the area. Despite several challenges, protocols proceeding via HAT are highly sought after as they allow for relatively easy activation of inert C–H bonds under mild conditions leading to a broader scope and higher functional group tolerance and sometimes complementary reactivity over methods relying on traditional transition metal catalysis. A number of methods operating via heteroatom-based HAT have been extensively reported over the past few years, while methods employing more challenging carbon analogues have been less explored. Recent developments of mild methodologies for generation of various carbon-centered radical species enabled their utilization in the HAT process, which, in turn, led to the development of remote C(sp3)–H functionalization reactions of alcohols, amines, amides and related compounds. This review covers mostly recent advances in C–H functionalization reactions involving the HAT step to carbon-centered radicals.

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C–H functionalization reactions enabled by hydrogen atom transfer to carbon-centered radicals

In this work, a photocatalytic strategy for a rapid and modular access to polycyclic indolones starting from readily available indoles is reported. This strategy relies on the use of redox-active esters in combination with an iridium-based photocatalyst under visible-light irradiation. The generation of alkyl radicals through decarboxylative single electron reductions enables intramolecular homolytic aromatic substitutions with a pending indole moiety to afford pyrrolo- and pyridoindolone derivatives under mild conditions. Furthermore, it was demonstrated that these radicals could also be engaged into cascades consisting of an intermolecular Giese-type addition followed by an intramolecular homolytic aromatic substitution to rapidly assemble valuable azepinoindolones.

https://chemistry-europe.onlinelibrary.wiley.com/doi/pdf/10.1002/chem.202001324

Photocatalytic Synthesis of Polycyclic Indolones

Radical Reactions in Alkaloid Synthesis: A Perspective from Carbon Radical Precursors

Total Syntheses of Dihydroindole Aspidosperma Alkaloids: Reductive Interrupted Fischer Indolization Followed by Redox Diversification.

The pseudoindoxyl sub-structural motif, amongst the large set of the indole class of alkaloids, represents a unique subset of the oxygenated indole class of the alkaloid family. A majority of this class of natural products contains complex bridged/polycyclic scaffolds with interesting biological profiles. They are thus attractive synthetic targets. Starting from 1963, twenty-eight natural products having the pseudoindoxyl scaffold have been isolated, among which the synthesis of 13 natural products has been accomplished. In this review, we highlight the completed as well as the formal total synthesis of the natural products with a spiro-pseudoindoxyl ring, with a focus on their development. The challenges and the future perspective based on the recent developments in the field will also be discussed. We strongly believe that this review will not only update but also attract the attention of researchers in dealing with the synthesis of pseudoindoxyl compounds.

Total synthesis of the pseudoindoxyl class of natural products.

The Aspidosperma alkaloids leuconoxine, melodinine E, and mersicarpine were synthesized. The approach features a key cascade radical reaction. A 1,5-hydrogen atom transfer is followed by spontaneous 5-exo-trig cyclization to construct the central indoline architecture. Late-stage differentiation of the radical cyclization product by chemoselective oxidation allows production of either the leuconoxine/melodinine E or mersicarpine structure.

Total Synthesis of Leuconoxine, Melodinine E, and Mersicarpine through a Radical Translocation–Cyclization Cascade

Organic semiconductor materials have recently gained momentum due to their non-toxicity, low cost, and sustainability. Xylindein is a remarkably photostable pigment secreted by fungi that grow on decaying wood, and its relatively strong electronic performance is enabled by π-π stacking and hydrogen-bonding network that promote charge transport. Herein, femtosecond transient absorption spectroscopy with a near-IR probe was used to unveil a rapid excited-state intramolecular proton transfer reaction. Conformational motions potentially lead to a conical intersection that quenches fluorescence in the monomeric state. In concentrated solutions, nascent aggregates exhibit a faster excited state lifetime due to excimer formation, confirmed by the excimer→charge-transfer excited-state absorption band of the xylindein thin film, thus limiting its optoelectronic performance. Therefore, extending the xylindein sidechains with branched alkyl groups may hinder the excimer formation and improve optoelectronic properties of naturally derived materials.

Ultrafast Dynamics and Photoresponse of a Fungi-Derived Pigment Xylindein from Solution to Thin Films.

Organic semiconductors have attracted increasing attention due to their low cost, solution processability, and tunable properties. Of special interest are molecules with enhanced environmental stab...

Ryan Kim

Papers

Total Synthesis of Leuconoxine, Melodinine E, and Mersicarpine through a Radical Translocation–Cyclization Cascade

Ultrafast Dynamics and Photoresponse of a Fungi-Derived Pigment Xylindein from Solution to Thin Films.

Role of Hydroxyl Groups in the Photophysics, Photostability, and (Opto)electronic Properties of the Fungi-Derived Pigment Xylindein