Recent advances in the synthesis of nitrogen heterocycles via radical cascade reactions using isonitriles as radical acceptors

Zhang, Bo; Studer, Armido

doi:10.1039/c5cs00083a

Cited by 695 publications

(236 citation statements)

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“…11 As an alternative, we chose ortho -isocyanobiaryls 23 as acceptors using reagents 1a and 1b as trifluoromethyl and perfluoroalkyl radical precursors to give 24 (Scheme 8). 16,17 The cascade works best in 1,4-dioxane at 70 °C with ( n -Bu) 4 NI as a radical initiator (Scheme 8). Mechanistically, chain initiation occurs by reduction of 1 by the iodide to generate a CF 3 -radical and ortho -iodobenzoate.…”

Section: Trifluoromethylation Via Set Reduction Of the Togni Reagentmentioning

confidence: 99%

Iodine(III) Reagents in Radical Chemistry

2017

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ConspectusThe chemistry of hypervalent iodine(III) compounds has gained great interest over the past 30 years. Hypervalent iodine(III) compounds show valuable ionic reactivity due to their high electrophilicity but also express radical reactivity as single electron oxidants for carbon and heteroatom radical generation. Looking at ionic chemistry, these iodine(III) reagents can act as electrophiles to efficiently construct C–CF3, X–CF3 (X = heteroatom), C–Rf (Rf = perfluoroalkyl), X–Rf, C–N3, C–CN, S–CN, and C–X bonds. In some cases, a Lewis or a Bronsted acid is necessary to increase their electrophilicity. In these transformations, the iodine(III) compounds react as formal “CF3+”, “Rf+”, “N3+”, “Ar+”, “CN+”, and “X+” equivalents. On the other hand, one electron reduction of the I(III) reagents opens the door to the radical world, which is the topic of this Account that focuses on radical reactivity of hypervalent iodine(III) compounds such as the Togni reagent, Zhdankin reagent, diaryliodonium salts, aryliodonium ylides, aryl(cyano)iodonium triflates, and aryl(perfluoroalkyl)iodonium triflates. Radical generation starting with I(III) reagents can also occur via thermal or light mediated homolysis of the weak hypervalent bond in such reagents. This reactivity can be used for alkane C–H functionalization. We will address important pioneering work in the area but will mainly focus on studies that have been conducted by our group over the last 5 years.We entered the field by investigating transition metal free single electron reduction of Togni type reagents using the readily available sodium 2,2,6,6-tetramethylpiperidine-1-oxyl salt (TEMPONa) as an organic one electron reductant for clean generation of the trifluoromethyl radical and perfluoroalkyl radicals. That valuable approach was later successfully also applied to the generation of azidyl and aryl radicals starting with the corresponding benziodoxole (Zhdankin reagent) and iodonium salts. In the presence of alkenes as radical acceptors, vicinal trifluoromethyl-, azido-, and arylaminoxylation products result via a sequence comprising radical addition to the alkene and subsequent TEMPO trapping. Electron-rich arenes also react with I(III) reagents via single electron transfer (SET) to give arene radical cations, which can then engage in arylation reactions. We also recognized that the isonitrile functionality in aryl isonitriles is a highly efficient perfluoroalkyl radical acceptor, and reaction of Rf-benziodoxoles (Togni type reagents) in the presence of a radical initiator provides various perfluoroalkylated N-heterocycles (indoles, phenanthridines, quinolines, etc.). We further found that aryliodonium ylides, previously used as carbene precursors in metal-mediated cyclopropanation reactions, react via SET reduction with TEMPONa to the corresponding aryl radicals. As a drawback of all these transformations, we realized that only one ligand of the iodine(III) reagent gets transferred to the substrate. To further increase atom-economy of such conversions, we ide...

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Section: Trifluoromethylation Via Set Reduction Of the Togni Reagentmentioning

confidence: 99%

Iodine(III) Reagents in Radical Chemistry

2017

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“…[1] Accordingly, ioscyanides are widely employed in valuable reactions that require a-addition, a-acidity,a nd ar eadiness to react with radicals.T hese include,P asserini [2] and Ugi reactions, [3] transition-metal catalyzed isocyanide insertion, [4] [3+ +2]-cycloaddition of activated methylene isocyanides with polar multiple bonds, [5] and radical insertions. [6] Recently,anew isocyano group reactivity profile was realized by Zhu and co-workers where the isocyano functional group formally acts as apolarized triple bond, allowing synthesis of imidazoles (Scheme 1, Eq. (1)).…”

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confidence: 99%

Cross‐Cycloaddition of Two Different Isocyanides: Chemoselective Heterodimerization and [3+2]‐Cyclization of 1,4‐Diazabutatriene

Yuan

Men

et al. 2016

Angewandte Chemie

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An ew cross-cycloaddition reaction between aw ide range of isocyanides and 2-isocyanochalcones (or analogues) was developed for the expeditious synthesis of pyrrolo [3,4-b]indoles under thermal conditions.O nt he basis of the experimental results and DFT calculations,amechanism for this domino reaction is proposed involving chemoselective heterodimerization of two different isocyanides to form 1,4-diazabutatriene intermediates,f ollowed by an intramolecular [3+ +2]-cycloaddition and 1,3-proton shift.

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“…[1] The carbene-like structure (Figure 1) [2] confers ambiphilic reactivity on the isocyanide carbon that manifests an exceptionally diverse reactivity for one functional group: metal insertion, [3] radical additions, [4] nucleophilic additions, [1] and electrophilic alkylations. [5] The high reactivity toward disparate reagents is particularly valuable for multicomponent reactions, [5] heterocycle synthesis, [6] and accessing acyclic nitrogenous scaffolds.…”

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confidence: 99%

Alkenyl Isocyanide Conjugate Additions: A Rapid Route to γ‐Carbolines

et al. 2017

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Isocyanides are exceptional building blocks whose wide deployment in multi-component and metal insertion reactions belies their limited availability. Addressing this deficiency is the first conjugate addition-alkylation method. An array of organolithiums, magnesiates, enolates, and metalated nitriles, add conjugately to β- and β, β-disubstituted arylsulfonyl alkenyl isocyanides to rapidly assemble diverse isocyanide scaffolds. The intermediate metalated isocyanides are efficiently trapped with electrophiles to generate substituted isocyanides incorporating contiguous tri- and tetra-substituted centers. The substituted isocyanides are ideally functionalized for elaboration into synthetic targets as illustrated by the three-step synthesis of the γ-carboline, N-methyl ingenine B.

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Recent advances in the synthesis of nitrogen heterocycles via radical cascade reactions using isonitriles as radical acceptors

Cited by 695 publications

References 97 publications

Iodine(III) Reagents in Radical Chemistry

Iodine(III) Reagents in Radical Chemistry

Cross‐Cycloaddition of Two Different Isocyanides: Chemoselective Heterodimerization and [3+2]‐Cyclization of 1,4‐Diazabutatriene

Alkenyl Isocyanide Conjugate Additions: A Rapid Route to γ‐Carbolines

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