Lochmann-Schlosser superbases

Toluene itself can be lithiated by w-BuLi-TMEDA at or above room temperature, and deprotonation occurs almost exclusively at the methyl group—about 10% ring metallation (mainly in the meta position) is observed with w-BuLi-TMEDA (Scheme 188) . At lower temperatures deprotonation is very slow , and the best conditions for achieving the metallation of toluene are the Lochmann-Schlosser superbases (see Section VI) °. 

In the case of a /3-phenyl substituted a-methoxy vinyl anion, the acetal 541 has been treated with the Lochmann-Schlosser superbase to promote /3-elimination followed by a-deprotonation. The corresponding anion has been trapped with tri-n-butylchlorostannane to give stereoselectively the stannane 542 (Scheme 146)823. 

Alkali metal alkyls, particularly n-butyl lithium, are the most frequently used reagents to form metallated intermediates.246 247 In certain cases (di- and triphenyl-methane, acetylene and 1-alkynes, cyclopentadiene) alkali metals can be directly applied. Grignard reagents are used to form magnesium acetylides and cyclopenta-dienyl complexes.248 Organolithium compounds with a bulky alkoxide, most notably M-BuLi-ferf-BuOK in THF/hexane mixture, known as the Lochmann-Schlosser reagent or LICKOR superbase, are more active and versatile reagents.249-252... 

A more versatile approach to 4,7-disubstituted dihydroacepentalenes 65 is via the stable acepentalene dianion 64 as an easily accessible intermediate. Dipotassium acepentalenediide 64 can be obtained in virtually quantitative yield by treatment of triquinacene 10 with the superbasic mixture of potassium f-pent-oxide and butyllithium [or even better potassium f-butoxide, butyllithium and tetramethylethylenediamine (TMEDA)] in hexane, the so-called Lochmann-Schlosser base (Scheme 15) [62, 63]. Mechanistically this transformation has... 

The nonsteroidal anti-inflammatory flurbiprofen 100 has been prepared via deprotonation of 3-fluorotoluene 98 with Schlosser-Lochmann superbase (Scheme 26.29) [182]. The selectivity improves significantly when a combination of ieri-butyllithium and potassium ferf-butoxide is used as the mixed-metal reagent. The deprotonation occurs at the least-hindered position adjacent to fluorine. Trapping of the organometallic intermediate with fluorodimethoxyborane-diethyletherate and hydrolysis affords the boronic acid, which is then employed in a Suzuki-Miyaura coupling reaction. Another superbase metalation of 99, now with a combination of LDA and potassium tert-butoxide, allows the deprotonation of the benzylic position, followed by carboxylation and a second metalation, and trapping with Mel to afford flurbiprofen 100. 

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