Iron(I) in Negishi Cross-Coupling Reactions

Adams, Christopher J.; Bedford, Robin B.; Carter, Emma; Gower, Nicholas J.; Haddow, Mairi F.; Harvey, Jeremy N.; Huwe, Michael; Cartes, Marcela; Mansell, Stephen M.; Mendoza, Carla; Murphy, D. M.; Neeve, Emily C.; Nunn, Joshua

doi:10.1021/ja303250t

Cited by 162 publications

(141 citation statements)

References 32 publications

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“…Although this reaction demonstrated the potential of the iron catalyst in the alkynylation of alkyl halides, significant synthetic limitations have remained, i.e., low functional group compatibility, the inapplicability of the reaction to secondary alkyl chlorides, and the need for overly elaborate protocols such as the slow addition of Grignard reagents at refluxing temperature. Herein we present the first example of SuzukiMiyaura coupling between alkynylborates and unactivated alkyl halides in the presence of an iron catalyst, 7,8 which overcomes these limitations to provide a facile route to alkyl-substituted functionalized alkynes in good to excellent yields (Scheme 1B).…”

Section: G5hmentioning

confidence: 99%

Iron-catalyzed Suzuki–Miyaura Coupling Reaction of Unactivated Alkyl Halides with Lithium Alkynylborates

2014

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A SuzukiMiyaura coupling reaction between unactivated alkyl halides and lithium alkynylborates was performed using an ironbisphosphine catalyst. The reaction shows high chemoselectivity and is applicable to a broad scope of substrates bearing electrophilic functional groups. A radical probe experiment using cyclopropylmethyl bromide was conducted to investigate the nature of the intermediate in the reaction, showing that an alkyl radical species is generated from the alkyl halide substrate.The SuzukiMiyaura coupling reaction has been widely used for the synthesis of functional organic molecules, such as pharmaceuticals, agrochemicals, and electronic materials. In particular, the SuzukiMiyaura coupling of alkynyl borate reagents has become recognized as a powerful tool for installing a CC triple bond moiety without altering other reactive functional groups on the substrates.2 Since Soderquist and Fürstner independently reported the palladium-catalyzed alkynylation between alkynyl borate reagents and aryl or alkenyl halides, 2b,2c the reaction has been successfully applied as a key step in the synthesis of natural products.3 However, while aryl and alkenyl halides have been widely employed in this alkynylation reaction, the use of unactivated alkyl halides has remained challenging due to their reluctance to oxidative addition and the competing nonproductive β-hydrogen elimination from the alkylmetal intermediate. Consequently, there has been no report on the use of alkynylborates in C sp C sp 3 bond-forming reactions with unactivated alkyl halides, despite extensive studies using various combinations of alkynyl donors and transition-metal catalysts such as palladium, 4a,4b,5a nickel, 4c,4d,5b cobalt, 5c5f and iron.5g,5hWe have previously reported a Sonogashira-type coupling between alkyl halides and alkynyl Grignard reagents with the ironbisphosphine catalyst [FeCl 2 (SciOPP)] 5g,6 (Scheme 1A). Although this reaction demonstrated the potential of the iron catalyst in the alkynylation of alkyl halides, significant synthetic limitations have remained, i.e., low functional group compatibility, the inapplicability of the reaction to secondary alkyl chlorides, and the need for overly elaborate protocols such as the slow addition of Grignard reagents at refluxing temperature. Herein we present the first example of SuzukiMiyaura coupling between alkynylborates and unactivated alkyl halides in the presence of an iron catalyst, 7,8 which overcomes these limitations to provide a facile route to alkyl-substituted functionalized alkynes in good to excellent yields (Scheme 1B).We began our investigation by evaluating the coupling reaction of chlorocycloheptane (1) and lithium (triisopropylsilyl)ethynyltrimethoxoborate (2), 9 readily prepared from the terminal alkyne, BuLi, and trimethyl borate, and found that by using 5 mol % of [FeCl 2 (SciOPP)] the target coupling product 3 was obtained in 80% yield, along with cycloheptene (4) and cycloheptane (5) (Table 1, Entry 1). Further investigation into the reaction conditions was...

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Section: G5hmentioning

confidence: 99%

Iron-catalyzed Suzuki–Miyaura Coupling Reaction of Unactivated Alkyl Halides with Lithium Alkynylborates

2014

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“…This is due to the strong chelating ability of the tridentate pincer ligand Bopa which, in turn, facilitates the mechanistic study. As in the Fe-TMEDA system for the coupling of less bulky Grignard reagent, the Fe(I) species (16) 19,20 and alkyl-alkyl Kumada coupling. 21 These Fe(I) species are supported by soft, neutral donors such as phosphine and N-heterocyclic carbene ligands which match well with the low-valent Fe(I) center.…”

mentioning

confidence: 99%

Iron Pincer Complexes as Catalysts and Intermediates in Alkyl–Aryl Kumada Coupling Reactions

et al. 2014

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Abstract. Iron-catalyzed alkyl-aryl Kumada coupling has developed into an efficient synthetic method, yet its mechanism remains vague. Here, we apply a bisoxazolinylphenylamido pincer ligand (Bopa) to stabilize the catalytically active Fe center, resulting in isolation and characterization of well-defined iron complexes whose catalytic roles are probed and confirmed. Reactivity studies of the iron complexes identifies an Fe(II) "ate" complex, [Fe(Bopa-Ph)(Ph) 2 ] -, as the active species for the oxidative addition of alkyl halide. Experiments using radicalprobe substrates and DFT computations reveal a bimetallic and radical mechanism for the oxidative addition. The kinetics of the coupling of an alkyl iodide with PhMgCl indicates that formation of the "ate" complex, rather than oxidative addition, is the turnover determining step. This work provides insights in iron-catalyzed cross coupling reactions of alkyl halides.3

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“…18 Further mechanistic studies are still needed, and the success of electronic tuning of the ligands will contribute to a deeper understanding of the nature of reactive organoiron species in future studies.…”

mentioning

confidence: 99%

Ligand-controlled Iron-catalyzed Cross Coupling of Benzylic Chlorides with Aryl Grignard Reagents

Kawamura

Nakamura

2013

Chemistry Letters

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The selective cross coupling of benzylic chlorides with aryl Grignard reagents has been achieved by using catalytic amounts of FeCl2 and electronically tuned ortho-phenylenebisphosphine ligands. Although electron-deficient ligands promoted the reductive homocoupling of benzylic halides, electron-rich ligands effectively promoted the desired cross-coupling reaction to afford the corresponding diarylmethanes in good to excellent yields.

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Iron(I) in Negishi Cross-Coupling Reactions

Cited by 162 publications

References 32 publications

Iron-catalyzed Suzuki–Miyaura Coupling Reaction of Unactivated Alkyl Halides with Lithium Alkynylborates

Iron-catalyzed Suzuki–Miyaura Coupling Reaction of Unactivated Alkyl Halides with Lithium Alkynylborates

Iron Pincer Complexes as Catalysts and Intermediates in Alkyl–Aryl Kumada Coupling Reactions

Ligand-controlled Iron-catalyzed Cross Coupling of Benzylic Chlorides with Aryl Grignard Reagents

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