Mesityllithium

• CAS: 5806-59-7
• Catalog Number: ACM5806597
• Category: Other Products
• Molecular Weight: 126.12
• Molecular Formula: C₉H₁₁Li
• Synonyms: MESITYLLITHIUM

Case Study

Mesityllithiu-mediated intramolecular synthesis of pyrrolo[1,2-b]isoquinolines

Lage, Sergio, et al. Synlett 2008.20 (2008): 3188-3192.

Mesityllithiu has been shown to be an efficient iodine-lithium exchange reagent. Thus, carbolithiation of 2-alkenyl-substituted N-(o-iodobenzyl)pyrroles has been accomplished, avoiding side reactions and providing pyrroloisoquinolines in high yields (80-92%), improving upon the results obtained with tert-butyllithium. The carbolithiation reaction requires the use of electron-deficient olefins. Mesityllithiu has also been investigated as an alternative to tert-butyllithium in Parham cyclizations with other internal electrophiles (aldehydes, ketones, esters, amides), proving to be more selective and efficient than tert-butyllithium.
The starting point for the synthesis was N-benzylpyrrole-2-carboxaldehyde, which was prepared by alkylation of commercially available pyrrole-2-carboxaldehyde with 2-iodo-4,5-dimethoxybenzyl bromide using standard procedures. Olefination of the aldehydes was achieved via a Wittig reaction with the corresponding phosphorus ylides to afford 2-vinyl-substituted N-(o-iodobenzyl)pyrroles in good overall yields. Carbolithiation of N-(o-iodobenzyl)pyrroles 3a-c with t-BuLi and TMEDA was investigated. However, although the iodine-lithium exchange occurred efficiently, the addition of tert-butyllithium to the unsubstituted olefin in 3a competed with the cyclization, isolating 7 and 6. The possibility of using bulkier, less nucleophilic reagents for the iodine-lithium exchange reaction was investigated. In this context, mesityllithium (MesLi) has been described as a strongly basic, non-nucleophilic, selective reagent. Mesityllithium is primarily used in organic synthesis as an LDA equivalent for deprotonation reactions, and there are few examples of its use in aromatic metalations or halogen-lithium exchange reactions. Thus, although the unsubstituted olefin 3a was also unreactive under these conditions, the lithium-iodine exchange with MesLi was effective to isolate the non-iodinated benzylpyrrole 6, but the addition of the reagent for the organolithium olefin was avoided. At higher temperatures (-20 or 0 °C), decomposition of the aryl lithium intermediate was observed. On the other hand, we were pleased to find that the cyclization of 3b and 3c proceeded smoothly at low temperatures, affording pyrroloisoquinolines 4b,c in high yields in only 5 min and avoiding side reactions.

Mesityllithium participates in regioselective α-lithiation

Hayashi, Mari, et al. (2011): 646-649.

α-Lithiation-methylation of unsymmetrical C-3-substituted 1-(tert-butoxycarbonyl)-1,4-dihydropyridines was studied. The yield and regioselectivity (C-2 vs. C-6) of the metalation depend on the C-3 substituent, the metalation base, and the reaction conditions. When the C-3 substituent is methyl or methoxy and mesityllithium is the base, lithiation-methylation occurs primarily at C-6. For strong ortho-C-3 substituents, i.e., C1, Br, or OCONEt2, metallation of phenyllithium occurs primarily at C-2. The α-aminoalkoxide functionality at C-3 acts only as a protecting group, forcing the lithiation to occur primarily at C-6. Two new trisubstituted pyridines, 3-[(N,N-diethylcarbamoyl)oxy]-2,4-dimethylpyridine and 2,4-dimethyl-3-pyridinecarboxaldehyde, were prepared by aromatization of a regioselective alkylated 1,4-dihydropyridine intermediate with o-tetrahydrobenzoquinone. A new approach to pyridine substitution was demonstrated with sulfur in refluxing decalin.
n-BuLi (0.73 mL, 1.32 mmol) was added to a solution of bromomesitylene (0.20 mL, 1.32 mmol) in THF (3 mL) at -78 °C. After 30 min, mesityllithium was added to a solution of dihydropyridine 4a (231 mg, 1.10 mmol) in 10 mL THF at -42 °C (CH3CN/CO2) via a double-ended needle. The mixture was stirred at -42 °C for 3 h. Iodomethane (0.21 mL, 3.3 mmol) was added and stirring was continued at -42 °C for 1 h and at room temperature for 30 min. Water (10 mL) was added and extracted with ether. The organic layers were combined and washed with sodium sulfate. Brine, dried (Mg2SO4), and concentrated to give a crude product which was purified by radial PLC (silica gel, hexane-10% EtOAc/hexane) to give 177 mg (72%) of 5 as a light yellow oil which was identical to the authentic product. A sample prepared from 2,5-lutidine contained approximately 7% of isomer 6 as determined by NMR analysis.

Custom Q&A

What is the molecular formula of Mesityllithium?

The molecular formula of Mesityllithium is C9H11Li.

When was Mesityllithium first created?

Mesityllithium was first created on October 26, 2006.

What is the IUPAC name of Mesityllithium?

The IUPAC name of Mesityllithium is lithium;1,3,5-trimethylbenzene-6-ide.

What is the computed InChIKey of Mesityllithium?

The computed InChIKey of Mesityllithium is RQLKAKQYERUOJD-UHFFFAOYSA-N.

How many hydrogen bond acceptor counts does Mesityllithium have?

Mesityllithium has 1 hydrogen bond acceptor count.

What is the exact mass of Mesityllithium?

The exact mass of Mesityllithium is 126.10207879 g/mol.

How many heavy atoms are in the structure of Mesityllithium?

There are 10 heavy atoms in the structure of Mesityllithium.

Does Mesityllithium have any defined atom stereocenter counts?

No, Mesityllithium does not have any defined atom stereocenter counts.

How many covalently-bonded unit counts does Mesityllithium have?

Mesityllithium has 2 covalently-bonded unit counts.

Is the compound canonicalized for Mesityllithium?

Yes, the compound is canonicalized for Mesityllithium.