Copper-catalyzed oxidative benzylic C-H cyclization via iminyl radical from intermolecular anion-radical redox relay

Abstract

Base-promoted C-H cleavage without transition metals opens a practical alternative for the one based on noble metals or radical initiators. The resulting carbanion can pass through radical addition to unsaturated bonds like C-N or C-C triple bonds, in which stoichiometric oxidants are needed. When in situ C-H cleavage meets catalytic carbanion-radical relay, it turns to be challenging but has not been accomplished yet. Here we report the combination of base-promoted benzylic C-H cleavage and copper-catalyzed carbanion-radical redox relay. Catalytic amount of naturally abundant and inexpensive copper salt, such as copper(II) sulfate, is used for anion-radical redox relay without any external oxidant. By avoiding using N-O/N-N homolysis or radical initiators to generate iminyl radicals, this strategy realizes modular synthesis of N-H indoles and analogs from abundant feedstocks, such as toluene and nitrile derivatives, and also enables rapid synthesis of large scale pharmaceuticals.

Tandem Hydroamination/Cyclization Access to N-2(5H)-Furanone Derivatives for COX-2 Inhibitor

“…According to the upper outcomes, a possible principle for this tandem reaction was as illustrated in Scheme . ,, Initially, the phenylacetylene was excited by Cu salt to produce the intermediate I , and subsequently experienced intramolecular Sonogashira reaction, generating Cu (III) intermediate II . This transition state further assaulted the electron-deficient terminal alkyne catalyzed by copper catalyst. , By removing a proton of the amide N–H from the intermediate III , hydroamination of the CC triple bond was formatted by coordination of Cu­(I) with the alkynyl group, leading to the intramolecular endocyclization of ( S )-6-methoxy-1,2-diphenyl-1H-furo­[3,4- b ]­pyrrol-4­(6 H )-one IV accompanied with Cu­(I) reproduction. , The generation of intermediate states ( I – IV ) have been determined by ESI/MS analysis, demonstrating the theory in Scheme .…”

Oxime‐Derived Iminyl Radicals in Selective Processes of Hydrogen Atom Transfer and Addition to Carbon‐Carbon π‐Bonds

“…In addition, synthetic potential of some types of iminyl radicals reactivity, such as intermolecular NÀ O and NÀ N coupling is still to be realized for oxime-derived iminyl radicals. [55,56,[161][162][163][164]…”

“…Future development areas of the oxime‐derived iminyl radicals chemistry include: (1) the development of mild conditions for the use of easily accessible oxime derivatives as iminyl radicals precursors, (2) further mechanistic studies of complicated radical reactions of oximes involving N−O bond cleavage (some representative examples of such processes are discussed in “Other reactions of oxime‐derived iminyl radicals” section), (3) the development of new photocatalytic systems, especially those based on non‐precious metals, metal‐free systems, or recyclable heterogenous photocatalysts (4) the development of electrochemical approaches to the generation of iminyl radicals. In addition, synthetic potential of some types of iminyl radicals reactivity, such as intermolecular N−O and N−N coupling is still to be realized for oxime‐derived iminyl radicals [55,56,161–164] …”

Synthesis of Indoles through Domino Reactions of 2‐Fluorotoluenes and Nitriles

“…Our method enables the preparation of indoles bearing substituents at each position on the indole backbone. This novel method for indole synthesis complements classic routes to 2‐substituted indoles, such as the Fischer, Gassman, Hegedus, Madelung, and Reissert indole syntheses . Among these, our synthesis stands out for its conciseness, convergent nature, and avoidance of low temperatures, which are difficult to access on scale.…”