Sterically facilitated meta-lithiation of arenes, containing electron-donating groups

Antonov, Alexander S.; Bardakov, Victor G.; Mulloyarova, Valeriia V.

doi:10.1016/j.jorganchem.2019.121068

Cited by 4 publications

(7 citation statements)

References 11 publications

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“…The o -methoxy groups in it have two advantages compared to the NMe 2 counterparts. They have a significantly greater acidifying ability and much higher conformational mobility that allows the realization of the DoM effect even after the first lithiation …”

Section: Resultsmentioning

confidence: 99%

“…They have a significantly greater acidifying ability and much higher conformational mobility that allows the realization of the DoM effect even after the first lithiation. 21 Metalation of 2,7-bis(methylthio) DMAN 5 results in the deprotonation of the SMe groups exclusively. This is evidenced by the isolation of compounds 16 [as an inseparable mixture; the NMR content of the ethylated species based on a triplet signal at 1.37 ppm due to Et is as large as 67% (see Figure S25)] and 17 (in its pure form) after treatment of the crude reaction mixture with the corresponding electrophiles (Scheme 5).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Organometallic Synthesis of 2,3,6,7-Tetrasubstituted 1,8-Bis(dimethylamino)naphthalenes for Investigation of the Double Buttressing Effect in Proton Sponges

et al. 2022

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The lithiation of 2,7-disubstituted derivatives of 1,8bis(dimethylamino)naphthalene (DMAN, proton sponge) bearing potentially ortho-directing OMe, NMe 2 , and SMe groups was studied. It has been shown that OMe groups facilitate selective dual βlithiation of the naphthalene moiety while the 2(7)-NMe 2 groups allow only monolithiation presumably due to the decreased acidity of the ring C−H bonds and conformational immobilization after coordination to the lithium atom. In contrast, the SMe groups provided no ring lithiation and underwent deprotonation of their methyl fragment. The first representatives of previously unknown 2,3,6,7-tetrasubstituted DMANs have been synthesized in good yield after treatment of 2,7-dimethoxy-3,6-dilithio DMAN with the appropriate electrophiles (MeI, Me 2 S 2 , Me 3 SiCl, DMF, etc.). Because the exceedingly high basicity of 2,7-dimethoxy DMAN is commonly attributed to the so-called "buttressing effect" (BE), the availability of 2,3,6,7-tetrasubstituted species provided the first opportunity to study the double BE version. Using X-ray diffraction and basicity measurements, we showed that due to the high conformational mobility of the methoxy groups, the most striking manifestations of double BE are the strong planarization of peri-NMe 2 groups and a significant decrease in basicity, while the length and the other properties of the intramolecular NHN hydrogen bond in the corresponding protonated species undergo minor changes.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Organometallic Synthesis of 2,3,6,7-Tetrasubstituted 1,8-Bis(dimethylamino)naphthalenes for Investigation of the Double Buttressing Effect in Proton Sponges

et al. 2022

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“…Thus, we expect that the reactivity of sterically strained oximes 1c and 1s will be comparable (if not superior) to 1a in real experimental conditions. Keeping in mind that SiMe 3 can be easily introduced to the NMe 2 group in the ortho - or peri -position via organometallic reagents [ 28 ], we believe that the presented findings will open up a simple way for the synthesis of novel polynuclear isoxazoles.…”

Section: Resultsmentioning

confidence: 99%

Sterically Facilitated Intramolecular Nucleophilic NMe2 Group Substitution in the Synthesis of Fused Isoxazoles: Theoretical Study

et al. 2020

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The influence of steric repulsion between the NMe2 group and a second ortho-(peri-)substituent in the series of 1-dimethylaminonaphthalene and N,N-dimethylanilene ortho-oximes on the ease of the NMe2 group’s intramolecular nucleophilic substitution is studied. Possible reaction intermediates for three mechanisms are calculated (ωB97xd/def-2-TZVP), and their free Gibbs energies are compared to model reaction profiles. Supporting experiments have proved the absence of studied reactivity in the case of simple 2-dimethylaminobenzaldoxime, which allowed us to establish reactivity limits. The significant facilitation of NMe2 group displacement in the presence of bulky substituents is demonstrated. The possibility of fused isoxazoles synthesis via the intramolecular nucleophilic substitution of a protonated NMe2 group in the aniline and naphthalene series is predicted.

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“…DMF generally provides an excellent conversion of organolithiums into the corresponding aldehydes, even in the case of sterically hindered molecules. [30,39,40] It should be noted that at lower temperatures, the reaction of 5 with DMF in n-hexane is incomplete after 24 hours. That is why this data is not included in Table 4.…”

Section: Runmentioning

confidence: 99%

“Buttressing Effect” in the Halogen‐Lithium Exchange in ortho‐Bromo‐N,N‐dimethylanilines and Related Naphthalenes

Meshalkin,

Tsybulin,

Bardakov

et al. 2024

Chemistry A European J

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Non‐covalent interactions such as coordination of an organolithium reagent by a directing group and steric repulsion of substituents strongly affect the halogen‐lithium exchange process. Here we present the manifestation of the “buttressing effect” – an indirect interaction between two substituents issued by the presence of a third group – and its influence on the ease and selectivity of the bromine‐lithium exchange and the reactivity of formed aryllithiums. The increase of the size of the “buttressing” substituent strongly affects the conformation of a NMe2 group, forcing it to hinder ortho‐bromine and thus slowing down the exchange. In naphthalene substrates bearing two bromines, this suppresses regioselectivity of the reaction. The “buttressing effect” forces formed aryllithiums to deaggregate, thus boosting their reactivity. This facilitates the decomposition via protolisys by ethereal solvents even at low temperatures and in some cases initiates fast Wurtz‐Fittig coupling.

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Sterically facilitated meta-lithiation of arenes, containing electron-donating groups

Cited by 4 publications

References 11 publications

Organometallic Synthesis of 2,3,6,7-Tetrasubstituted 1,8-Bis(dimethylamino)naphthalenes for Investigation of the Double Buttressing Effect in Proton Sponges

Organometallic Synthesis of 2,3,6,7-Tetrasubstituted 1,8-Bis(dimethylamino)naphthalenes for Investigation of the Double Buttressing Effect in Proton Sponges

Sterically Facilitated Intramolecular Nucleophilic NMe2 Group Substitution in the Synthesis of Fused Isoxazoles: Theoretical Study

“Buttressing Effect” in the Halogen‐Lithium Exchange in ortho‐Bromo‐N,N‐dimethylanilines and Related Naphthalenes

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