Synthesis of pentasubstituted 2-aryl pyrroles from boryl and stannyl alkynes <i>via</i> one-pot sequential Ti-catalyzed [2 + 2 + 1] pyrrole synthesis/cross coupling reactions

Cheng, Yukun; Klein, Channing; Tonks, Ian A.

doi:10.1039/d0sc01576h

Cited by 14 publications

(13 citation statements)

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“…Given that diazatitanacyclohexadiene intermediate formation is regioselective, 32,[55][56][57] this method could be used to prepare regioisomeric a-diimines through different combinations of alkynes, imidos, and nitrosos (Fig. 7).…”

Section: In Situ Multicomponent Diimine Synthesismentioning

confidence: 99%

α-Diimine synthesis via titanium-mediated multicomponent diimination of alkynes with C-nitrosos

et al. 2022

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Section: In Situ Multicomponent Diimine Synthesismentioning

confidence: 99%

α-Diimine synthesis via titanium-mediated multicomponent diimination of alkynes with C-nitrosos

et al. 2022

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“…This modularity enables the direct synthesis of regioisomeric pyrroles such as 21b and 21f . Additional selective heterocouplings have subsequently been reported with boryl and stannyl alkynes, yielding 2-boryl- and 2-stannyl-substituted pyrroles, respectively …”

Section: Multicomponent Reactions With Alkynesmentioning

confidence: 99%

Ti-Catalyzed and -Mediated Oxidative Amination Reactions

Tonks

2021

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: Titanium is an attractive metal for catalytic reaction development: it is earth-abundant, inexpensive, and generally nontoxic. Howeverlike most early transition metalscatalytic redox reactions with Ti are difficult because of the stability of the high-valent Ti IV state. Understanding the fundamental mechanisms behind Ti redox processes is key for making progress toward potential catalytic applications. This Account details recent progress in Ti-catalyzed (and -mediated) oxidative amination reactions that proceed through formally Ti II /Ti IV catalytic cycles. This class of reactions is built on our initial discovery of Ti-catalyzed [2 + 2 + 1] pyrrole synthesis from alkynes and azobenzene, where detailed mechanistic studies have revealed important factors that allow for catalytic turnover despite the inherent difficulty of Ti redox. Two important conclusions from mechanistic studies are that (1) low-valent Ti intermediates in catalysis can be stabilized through coordination of π-acceptor substrates or products, where they can act as "redox-noninnocent" ligands through metal-toligand π back-donation, and (2) reductive elimination processes with Ti proceed through π-type electrocyclic (or pericyclic) reaction mechanisms rather than direct σ-bond coupling.The key reactive species in Ti-catalyzed oxidative amination reactions are Ti imidos (TiNR), which can be generated from either aryl diazenes (RNNR) or organic azides (RN 3 ). These Ti imidos can then undergo [2 + 2] cycloadditions with alkynes, resulting in intermediates that can be coupled to an array of other unsaturated functional groups, including alkynes, alkenes, nitriles, and nitrosos. This basic reactivity pattern has been extended into a broad range of catalytic and stoichiometric oxidative multicomponent coupling reactions of alkynes and other reactive small molecules, leading to multicomponent syntheses of various heterocycles and aminated building blocks. For example, catalytic oxidative coupling of Ti imidos with two different alkynes leads to pyrroles, while stoichiometric oxidative coupling with alkynes and nitriles leads to pyrazoles. These heterocycle syntheses often yield substitution patterns that are complementary to those of classical condensation routes and provide access to new electron-rich, highly substituted heteroaromatic scaffolds. Furthermore, catalytic oxidative alkyne carboamination reactions can be accomplished via reaction of Ti imidos with alkynes and alkenes, yielding α,β-unsaturated imine or cyclopropylimine building blocks. New catalytic and stoichiometric oxidative amination methods such as alkyne α-diimination, isocyanide imination, and ring-opening oxidative amination of strained alkenes are continuously emerging as a result of better mechanistic understanding of Ti redox catalysis.Ultimately, these Ti-catalyzed and -mediated oxidative amination methods demonstrate the importance of examining oftencontinued...

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“…Follow-up studies found that heteroatom-substituted alkynes 8 (ECCR, where E ¼ SiR 3 , SnR 3 , 9-BBN) are suitable partners for highly chemo-and regioselective heterocoupling (Fig. 4) either with 38 or without 40,41 chelating directing groups. The resulting heteroatom-substituted pyrroles can be further functionalized, allowing for the synthesis of a wide variety of multi-substituted pyrroles, including natural products such as Lamellarin R. Catalyst control of chemo-and regioselectivity has proven more challenging, although a recent report used statistical analysis (ISPCA) 42 to identify pyridinesubstituted catalysts that could selectively homocouple phenylpropyne to 2,5-Me 2 -1,3,4-Ph 3 -1H-pyrrole.…”

Section: Pyrroles Furans and Thiophenesmentioning

confidence: 99%

Multicomponent syntheses of 5- and 6-membered aromatic heterocycles using group 4–8 transition metal catalysts

et al. 2021

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Synthesis of pentasubstituted 2-aryl pyrroles from boryl and stannyl alkynes via one-pot sequential Ti-catalyzed [2 + 2 + 1] pyrrole synthesis/cross coupling reactions

Abstract: Multisubstituted pyrroles are commonly found in many bioactive small molecule scaffolds, yet the synthesis of highly- substituted pyrrole cores remains challenging. Herein, we report an efficient catalytic synthesis of 2-heteroatom-substituted...

Cited by 14 publications

References 51 publications

α-Diimine synthesis via titanium-mediated multicomponent diimination of alkynes with C-nitrosos

α-Diimine synthesis via titanium-mediated multicomponent diimination of alkynes with C-nitrosos

Ti-Catalyzed and -Mediated Oxidative Amination Reactions

Multicomponent syntheses of 5- and 6-membered aromatic heterocycles using group 4–8 transition metal catalysts

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