Reductive Lithiation and Multilithiated Compounds in Synthesis

Azzena, Ugo; Pisano, Luisa

doi:10.1002/9783527667512.ch12

Cited by 7 publications

(4 citation statements)

References 89 publications

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“…Their protocol was found to be applicable to the ring-opening dilithiations of 4-heteroatom-substituted dibenzothiins, [19] dibenzofuran, [20,21] and so on. [22][23][24][25] However, there had been no reports about the ringopening of indoles by the electron injection from alkali metal.…”

Section: Aromatic Metamorphosis Of Indoles Through Electron Injection...mentioning

confidence: 99%

Electron injection for aromatic metamorphosis of indole

Yorimitsu

2020

J Chinese Chemical Soc

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Aromatic metamorphosis, endocyclic transformations of aromatic compounds, has been emerging as a new synthetic strategy in organic synthesis. This counterintuitive strategy necessitates very powerful reactions that can surmount aromaticity and the strong carbon–heteroatom bonds of the heteroaromatic rings. This Short Account describes the development of the currently most powerful elementary reaction for aromatic metamorphosis, which is electron injection from lithium metal. Exceptionally robust and aromatic N‐phenylindole is subjected to the electron injection, resulting in the formation of the corresponding dianionic intermediate through reductive ring‐opening. A trapping reaction of the dianionic intermediate with organoboronic acid pinacol esters provides benzazaborines, which are attractive BN‐isosteres of naphthalenes. The electron injection helps establishing aromatic metamorphosis as a reliable synthetic methodology to provide novel useful molecules.

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Section: Aromatic Metamorphosis Of Indoles Through Electron Injection...mentioning

confidence: 99%

Electron injection for aromatic metamorphosis of indole

Yorimitsu

2020

J Chinese Chemical Soc

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“…In 1976, Freeman and Hutchinson introduced a new radical anion generated by reduction of Di- tert -ButylBiphenyl (DBB) with lithium metal to produce Lithium Di- tert -ButylBiphenylide (LiDBB). They demonstrated the superiority of this reagent for the generation of alkyllithium reagents from alkyl chlorides when compared with lithium naphthalide (LiN). , The LiDBB system exhibited fewer side reactions with the alkyllithium reagent than LiN, and the higher reduction potential of the DBB anion extended the substrate scope . Several other radical anions have been used to generate alkyllithium reagents, and methods with lithium metal and a catalytic arene have been successfully developed. , Stoichiometric LiDBB is still the reagent of choice for the reductive generation of sensitive alkyllithium regents from alkyl chlorides and alkyl phenyl sulfides. , It is also employed for many other single electron reduction processes .…”

Section: Introductionmentioning

confidence: 99%

“…An advantage of LiDBB and the reason for its continued popularity is LiDBB can generate sensitive alkyllithium reagents at low temperature with higher yields than any other reagent (Figure ). We have investigated the generation of LiDBB solutions and their stabilities to improve upon the utility of this reagent.…”

Section: Introductionmentioning

confidence: 99%

Generation, Stability, and Utility of Lithium 4,4′-Di-tert-butylbiphenylide (LiDBB)

Hill

Rychnovsky

2016

J. Org. Chem.

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Several procedures were evaluated for the preparation of lithium 4,4'-di-tert-butylbiphenylide (LiDBB, Freeman's reagent) from lithium metal and 4,4'-di-tert-butylbiphenyl (DBB) in THF. Solutions with nominal concentration of 0.4 and 1.0 M were formed. The stability of LiDBB solutions was evaluated over time, and the gradual uptake of lithium metal was observed. At 0 °C the LiDBB solutions were stable for over a week in THF. At 20 °C the LiDBB solution underwent various decomposition pathways, which led to uptake of more lithium metal and the accumulation of side products. These decomposition pathways were studied, and the importance of ethene in the destruction of THF by LiDBB was observed. On a practical note, LiDBB solutions in THF were stable and effective for over a week at 0 °C or for more than 37 weeks when stored under argon at -25 °C. These observations will extend the utility of LiDBB as a reagent in organic synthesis.

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“…One of the most versatile methods known for generating organolithiums is by the reductive lithiation of phenyl thioethers, the replacement of a C–S bond with a C–Li bond, using aromatic radical-anions as the source of the electron (Scheme ). − Aromatic radical-anions including: lithium naphthalenide (LN), lithium 1-( N , N -dimethylamino)naphthalenide (LDMAN), and lithium p , p ′-di- tert -butylbiphenylide (LDBB) are currently in use. The superiority of alkyl phenyl thioethers as substrates for reductive lithiation arises from their almost unique ease of construction as well as the ability of the phenylthio group to enter a molecule as a nucleophile, electrophile, or radical …”

Section: Introductionmentioning

confidence: 99%

Reductive Lithiation in the Absence of Aromatic Electron Carriers. A Steric Effect Manifested on the Surface of Lithium Metal Leads to a Difference in Relative Reactivity Depending on Whether the Aromatic Electron Carrier Is Present or Absent

et al. 2015

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One of the most widely used methods of preparation of organolithium compounds is by the reductive lithiation of alkyl phenyl thioethers or, usually less conveniently, alkyl halides with either aromatic radical-anions of lithium or lithium metal in the presence of an aromatic electron-transfer catalyst. Here we present results showing that lithium dispersion can achieve reductive lithiation in the absence of the electron-transfer agent. This procedure is more efficient, and surprisingly, the order of reactivity of substrates is reversed depending on whether the electron-transfer agent is present or absent. For example, in the presence of a preformed radical-anion, tert-butyl phenyl sulfide cleaves significantly faster than methyl phenyl sulfide, whereas in the absence of the radical-anion, it is just the opposite. Density functional theory calculations reveal that the exothermicity of the cleavage of the C-S bond in alkyl phenyl thioethers on the lithium surface is dependent on the size of the alkyl group, the smaller the alkyl group the greater the exothermicity. The increased reactivity is attributed to the smaller steric repulsion between the alkyl group and the lithium surface. The methodology includes, but may not be limited to, the lithium dispersion reductive lithiation of phenyl thioethers, alkyl chlorides, acrolein diethyl acetal, and isochroman.

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Reductive Lithiation and Multilithiated Compounds in Synthesis

Cited by 7 publications

References 89 publications

Electron injection for aromatic metamorphosis of indole

Electron injection for aromatic metamorphosis of indole

Generation, Stability, and Utility of Lithium 4,4′-Di-tert-butylbiphenylide (LiDBB)

Reductive Lithiation in the Absence of Aromatic Electron Carriers. A Steric Effect Manifested on the Surface of Lithium Metal Leads to a Difference in Relative Reactivity Depending on Whether the Aromatic Electron Carrier Is Present or Absent

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