Transition‐Metal‐Free Heterobiaryl Synthesis via Aryne Coupling

Saied, Tarak; Demangeat, Catherine; Panossian, Armen; Leroux, Frédéric R.; Fort, Yves; Comoy, Corinne

doi:10.1002/ejoc.201900130

Cited by 8 publications

(3 citation statements)

References 115 publications

(146 reference statements)

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“…The formation of 1h likely occurs through aryne generation from ortho -bromolithiobenzene by the elimination of LiBr and the reaction of the highly unstable intermediate with remaining the ortho -bromolithiobenzene and a subsequent reaction with Bu 3 SnCl. Aryne intermediates have been proposed in other works and applied for the preparation of biphenyl systems. − For the system under investigation here, we propose a mechanism for the formation of 1h that is analogous to the previous proposals, , which involves the formation of (2′-bromo-[1,1′-biphenyl]-2-yl)lithium that then reacts with Bu 3 SnCl (Scheme ).…”

Section: Resultsmentioning

confidence: 59%

Synthesis of Long-Chain Alkanoyl Benzenes by an Aluminum(III) Chloride-Catalyzed Destannylative Acylation Reaction

2021

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This paper describes the facile synthesis of haloaryl compounds with long-chain alkanoyl substituents by the destannylative acylation of haloaryls bearing tri-n-butyltin (Bu 3 Sn) substituents. The method allows the synthesis of many important synthons for novel functional materials in a highly efficient manner. The halo-tri-n-butyltin benzenes are obtained by the lithium−halogen exchange of commercially available bis-haloarenes and the subsequent reaction with Bu 3 SnCl. Under typical Friedel−Crafts conditions, i.e., the presence of an acid chloride and AlCl 3 , the haloaryls are acylated through destannylation. The reactions proceed fast (<5 min) at low temperatures and thus are compatible with aromatic halogen substituents. Furthermore, the method is applicable to para-, meta-, and ortho-substitution and larger systems, as demonstrated for biphenyls. The generated tin byproducts were efficiently removed by trapping with silica/KF filtration, and most long-chain haloaryls were obtained chromatography-free. Molecular structures of several products were determined by X-ray single-crystal diffraction, and the crystal packing was investigated by mapping Hirshfeld surfaces onto individual molecules. A feasible reaction mechanism for the destannylative acylation reaction is proposed and supported through density functional theory (DFT) calculations. DFT results in combination with NMR-scale control experiments unambiguously demonstrate the importance of the tin substituent as a leaving group, which enables the acylation.

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Section: Resultsmentioning

confidence: 59%

Synthesis of Long-Chain Alkanoyl Benzenes by an Aluminum(III) Chloride-Catalyzed Destannylative Acylation Reaction

2021

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“…Encouraged by this result, we wanted to apply these conditions to the hitherto unknown 2-chloro analog 10 (Scheme 5), for which a synthetic access had to be developed. Halogenation of 2-chloro-5-bromopyridine (9) was not an option since trapping of the lithiated species with a bromination reagent such as NBS would result in an oxidative dimerization [21][22][23][24]. Finally, the Sandmeyer reaction of commercially available aminopyridine 35 yielded 10 in excellent yields using water-free reaction conditions (Scheme 5, condition b) [25], while under classical Sandmeyer conditions in aqueous medium, only moderate yields were observed due to low solubility of the starting material 35 and side-product formation (see Supplementary Materials).…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis of Floyocidin B: 4,5-Regioselective Functionalization of 2-Chloropyridines

et al. 2023

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The recently discovered natural product (NP) (+)-floyocidin B with antimicrobial activity against Mycobacterium tuberculosis displays a hitherto unknown dihydroisoquinolinone scaffold in the class of the epoxyquinone NPs. The 4,5-regioselective functionalization of 2-chloropyridines was identified as a suitable strategy leading to the total syntheses of (+)-floyocidin B and analogs. In this paper, we present the long and winding evolution process to the final synthetic pathway, including model systems for route scouting and elucidation of side products, which enabled us to understand the unique reactivity of this unprecedented scaffold. A special focus was laid on method studies with different 2-chloropyridines, disclosing an unexpected effect of the 2-chloro substituent on the regioselectivity compared to 2-unsubstituted or carbon-substituted pyridines. Finally, a head-to-head comparison with the previously described synthesis of all four stereoisomers of the NP (−)-avicennone C revealed significant differences in the reactivity of these structurally closely related scaffolds.

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“…There is no doubt that the most common strategies to construct a biaryl scaffold involve transition metal‐catalysed reactions . However, beyond the above mentioned general considerations on the use of these catalysts, the limited substituents tolerance, with specific reference to the presence of extra halogens, strongly contributes to incentive the development of alternative methods to prepare halogenated biaryls, although some sporadic transition metal‐catalysed and metal free, strategies with limited scope have already been reported.…”

Section: Introductionmentioning

confidence: 99%

Scalable Multicomponent Synthesis of (Hetero)aryl‐Substituted Phenyls: Focus on Metal‐Free Halogenated Biaryls, 3‐Arylindoles, and Isourolithine A Synthesis

et al. 2019

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In the context of the growing interest of the scientific community for the development of sustainable synthetic strategies to access aromatic structures, we present a practical and metal-free approach to (hetero)biaryls which exploits the advantages of multicomponent reactions in sustainable solvents. In situ acid-catalysed generation of (hetero)aryl acetoxy dienes from the corresponding (hetero)arylidene acetones in a metal vessel, followed by Diels-Alder reaction using an electronpoor alkyne as dienophile, delivers the expected aromatic prod- [a] 7711 Scheme 1. Thermal activation of alkynes in multicomponent metal-free synthesis of (hetero)aryl-substituted phenyls in metal vessel. 7712 field of research under hyperbaric, thermal and microwave activation, [48][49][50] due to the scarce reactivity of this compound with consequently unsatisfying yields. [51] Eur.

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Transition‐Metal‐Free Heterobiaryl Synthesis via Aryne Coupling

Cited by 8 publications

References 115 publications

Synthesis of Long-Chain Alkanoyl Benzenes by an Aluminum(III) Chloride-Catalyzed Destannylative Acylation Reaction

Synthesis of Long-Chain Alkanoyl Benzenes by an Aluminum(III) Chloride-Catalyzed Destannylative Acylation Reaction

Total Synthesis of Floyocidin B: 4,5-Regioselective Functionalization of 2-Chloropyridines

Scalable Multicomponent Synthesis of (Hetero)aryl‐Substituted Phenyls: Focus on Metal‐Free Halogenated Biaryls, 3‐Arylindoles, and Isourolithine A Synthesis

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