Palladium-Catalyzed Ullmann Cross-Coupling of β-Iodoenones and β-Iodoacrylates with <i>o</i>-Halonitroarenes or <i>o</i>-Iodobenzonitriles and Reductive Cyclization of the Resulting Products To Give Diverse Heterocyclic Systems

Khan, Faiyaz; Dlugosch, Michael; Liu, Xin; Khan, Marium; Banwell, Martin G.; Ward, Jas S.; Carr, P.D.

doi:10.1021/acs.orglett.8b01015

Cited by 17 publications

(21 citation statements)

References 30 publications

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“…[4] This coupling reaction catalyzed by CuI proceeded smoothly to give enol 9 in 93 % yield. Subsequent treatment of 9 with I 2 ‐PPh 3 afforded 6 in 89 % yield [5] . Next, Nozaki–Hiyama–Kishi coupling reaction between iodide 6 and aldehyde 10 produced secondary alcohol 11 in 78 % yield [6] .…”

Section: Figurementioning

confidence: 99%

Total Synthesis of Cochlearol B via Intramolecular [2+2] Photocycloaddition

et al. 2021

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Herein, we describe the first total synthesis of cochlearol B, a meroterpenoid natural product featuring a 4/5/ 6/6/6-fused pentacyclic structure. Key steps, oxidative cyclization and subsequent intramolecular [2+2] photocycloaddition, which constructed the pentacyclic structure in highly stereoselective manner, allowed efficient access to cochlearol B with the longest linear sequence of 16 steps, and in 9 % overall yield. Single-crystal X-ray crystallographic analysis clearly confirmed the stereochemistry of cochlearol B.

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Section: Figurementioning

confidence: 99%

Total Synthesis of Cochlearol B via Intramolecular [2+2] Photocycloaddition

et al. 2021

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“…Investigations of intramolecular variants of the title XECs are also likely to be profitable areas of research. Furthermore, our recent discovery that o -halobenzonitriles are also capable of engaging in palladium-catalyzed Ulllmann cross-coupling reactions suggests that access to other types of heterocyclic systems (e.g., 87 ) will become available through the reductive cyclization of such products. Of course, the development of a more detailed mechanistic understanding of the palladium-catalyzed Ullmann cross-coupling reaction, including the role of additives such as cuprous iodide, will provide an important basis for further developments in the area.…”

Section: Future Prospectsmentioning

confidence: 99%

The Palladium-Catalyzed Ullmann Cross-Coupling Reaction: A Modern Variant on a Time-Honored Process

et al. 2018

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Cross-coupling reactions, especially those that are catalyzed by palladium, have revolutionized the way in which carbon-carbon bonds can be formed. The most commonly deployed variants of such processes are the Suzuki-Miyaura, Mizoroki-Heck, Stille, and Negishi cross-coupling reactions, and these normally involve the linking of an organohalide or pseudohalide (such as a triflate or nonaflate) with an organo-metallic or -metalloid such as an organo-boron, -magnesium, -tin, or -zinc species. Since the latter type of coupling partner is often prepared from the corresponding halide, methods that allow for the direct cross-coupling of two distinct halogen-containing compounds would provide valuable and more atom-economical capacities for the formation of carbon-carbon bonds. While the venerable Ullmann reaction can in principle achieve this, it has a number of drawbacks, the most significant of which is that homocoupling of the reaction partners is a competitive, if not the dominant, process. Furthermore, such reactions normally occur only under forcing conditions (viz., often at temperatures in excess of 250 °C). As such, the Ullmann reaction has seen only limited application in this regard, especially as a mid- to late-stage feature of complex natural product synthesis. This Account details the development of the palladium-catalyzed Ullmann cross-coupling reaction as a useful method for the assembly of a range of heterocyclic systems relevant to medicinal and/or natural products chemistry. These couplings normally proceed under relatively mild conditions (<100 °C) over short periods of time and, usually, to the exclusion of (unwanted) homocoupling events. The keys to success are the appropriate choice of coupling partners, the form of the copper metal employed, and the choice of reaction solvent. At the present time, the cross-coupling partners capable of engaging in the title reaction are confined to halogenated and otherwise electron-deficient arenes and, as complementary reactants, α- or β-halogenated, α,β-unsaturated aldehydes, ketones, esters, lactones, lactams, and cycloimides. Nitro-substituted (and halogenated) arenes, in particular, serve as effective participants in these reactions, and the products of their coupling with the above-mentioned carbonyl-containing systems can be manipulated in a number of different ways. Depending on the positional relationship between the nitro and carbonyl groups in the cross-coupling product, the reduction of the former group, which can be achieved under a range of different conditions, provides, through intramolecular nucleophilic addition reactions, including Schiff base condensations, access to a diverse range of heterocyclic systems. These include indoles, quinolines, quinolones, isoquinolines, carbazoles, and carbolines. Tandem variants of such cyclization processes, in which Raney cobalt is used as a catalyst for the chemoselective reduction (by dihydrogen) of nitro and nitrile groups (but not olefins), allow for the assembly of a range of structurally challenging nat...

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“…Subsequent treatment of 9 with I 2 -PPh 3 afforded 6 in 89 % yield. [5] Next, Nozaki-Hiyama-Kishi coupling reaction between iodide 6 and aldehyde 10 produced secondary alcohol 11 in 78 % yield. [6] Oxidation of 11, [7] followed by regioselective reduction with NaBH 4 , afforded hydroxyketone 13 in 70 % yield from 11.…”

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confidence: 99%