Superbase mixture of

The expedient and regioselective metalation of unprotected biphenyl-2-, -3-, and -4-carboxylic acids has been reported.59 Unprotected biphenyl-2-carboxylic acid has been cleanly metalated with. sex-butyllithium at the position adjacent to the carboxylate and can then be subjected to site-selective electrophilic substitution (Scheme 8). The remote C(2 )-position has been attacked by the superbasic mixture of n-BuLi and t-BuOK (LICKOR) in THF or benzene. The resulting dianion cyclizes to give the fluorenone skeleton. The mechanism of the metalation of homologous compounds, 2-(pyridin-3-yl)benzoic acid derivatives, with strong bases has also been discussed.60... 

Thioxanthene 305 is readily metallated by -butyllithium at the 9-position giving access to the 9-carboxylic acid and the ethyl thioether. The latter gives the 9-carbanion on treatment with the superbasic mixture of n-BuLi, /-PoNH, and KO/-Bu, and hence gives access to 9-thioethylthioxanthene-9-carboxylic acid (Scheme 49) <1998T2251>. 

Stereochemically pure allylsilanes and stannanes can also be obtained by metallation of suitable olefins with the superbasic mixture of butyllithium and potassium /fV/-butoxide followed by reaction with trimethylchlorosilane and tributylchlorostannane, respectively. In a representative example, 6-(2-tetrahydropyra-nyloxy)hex-l-ene is transformed into Z-(6-hydroxyhex-2-enyl)trimethylsilane through metallation with trimethyl-... 

The optional site selective metallation of fluorotoluenes158 with the superbasic mixture of butyllithium and potassium fert-butoxide has been applied to the synthesis of the anti-inflammatory and analgesic drug Flurbiprofen.171 3-Fluorotoluene is selectively metallated in the 4-position with LIC-KOR in THF at — 75 °C to afford, after reaction with fluorodimethoxyborane and hydrolysis, the corresponding boronic acid in 78% yield. A palladium-catalyzed coupling with bromobenzene gives the 2-fluoro-4-methylbiphenyl in 84% yield. This four-step sequence can also be contracted to a one-pot procedure with an overall yield of 79%. A double metallation with the superbasic mixture lithium diisopropylamide/potassium tert-butoxide (LIDA-KOR)172 173 is then required to produce flurbiprofen. 

As shown in Equation (62), 1,2-/fe(mcthylthio)bcnzene 338 was dimetallated using butyllithium or superbasic mixture of butyllithium/potassium r/-butoxide (LICKOR), and then quenched with dichlorodimethylsilane to obtain 1,5,3-benzodithiasilepin 339 <1999T14069>. 

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 dianion of dihydroacepentalene is of considerable interest as a potential precursor for the elusive hydrocarbon acepentalene, CioHe, which has been predicted to have a triplet diradical ground state. The corresponding dianion, CioHe ", is significantly more stable and can be generated in solution by treating triquinacene with a superbasic mixture of n-butyllithium and potassium t-pentoxide in the presence of tmeda [27]. More recently a crystalline sample of the dimethoxyethane solvate [ Li(DME) 2CioH6]2, 33, has been successfully prepared according to Eq.(l) by means of a transmetallation reaction between 4,7-bis(trimethylstannyl)-dihydroacepentalene and methyllithium in DME solution at -60 °C [28]. 

Toluene and Congeners. When alkylbenzene derivatives are submitted to metalation, the metal may effect deprotonation either at a benzylic or at a ring hydrogen site (preferably at the sterically unhindered meta or para positions). To avoid contamination by the ring-metalated derivative, a-deprotonation of toluene requires the superbase mixture of n-butyllithium/potassium ferf-butoxide. Use of TMEDA activated n-butyllithium, for example, gives rise... 

The violence of superbasic slurries towards functionalized organic molecules means that they are at their most effective with simple hydrocarbons they also tolerate ethers and fluoro substituents. LiCKOR will deprotonate allyUc, benzylic, vinylic, aromatic and cyclopropane C—H bonds with no additional assistance. From benzene, for example, it forms a mixture of mono and dimetallated compounds 617 and 618 (Scheme 241) . ( Li/K indicates metallation with a structurally ill-defined mixture of lithium and potassium.)... 

Benzofuranyl)pyrroles, 2-(2-thienyl)pyrroles , 2,2 -dipyrroles, 3-(2-pyr-rolyl)indoles , 2-(2-benzimidazolyl)pyrroles and2-(2-, 3- and4-pyridyl)pyrroles were prepared using this method. Reaction of alkynes (for example, propyne) or allene with ketoximes in a superbase system (MOH/DMSO) leads to 2,5-di- or 2,3,5-trisubstituted pyrroles Pyrroles and dipyrroles were synthesized also from corresponding dioximes and acetylene in a KOH/DMSO system It has also been shown that 1,2-dichloroeth-ane can serve as a source of acetylene in pyrrole synthesis. Oxime 52 in the system acetylene/RbOH/DMSO at 70 °C afforded a mixture of three pyrroles 53-55 in low yields (equation 23). The formation of product 53 occurred through recyclization of pyrrolopy-ridine intermediate. ... 

The synthesis of compounds 2a, 2b may be realized as a one-pot reaction of phenylacetylene with powdered tellurium in the superbasic medium (K0H-HMPTA-SnCl2-H20) (89TL441). The yield of the mixture of trans-and cfs-isomers is 15%. 

In isomerization reactions, an alkene is deprotonated to form an allyl anion, which is reprotonated to give the more stable alkene (double-bond migration). The most simple example is the isomerization of 1-butene producing a mixture of cis- and trans-2-butene (Scheme 3). Because the stability of the cis-allyl anion formed as an intermediate is greater than for the trans form, a high cis/trans ratio is observed for base-catalyzed reactions whereas for acid-catalyzed reactions the ratio is close to unity. Thus, the cis/trans ratio of the products has frequently been used as an indication of base-catalyzed reaction mechanisms. The carbanions formed in the course of such superbase reactions are not freely mobile in solution,... 

Alkenes lacking hydrogen atoms at allylic positions are much less acidic than ordinary unsaturated hydrocarbons. Superbases regioselectively exchange allylic protons in alkenes whenever there is a choice. However, a few examples of metallation of alkenic C-H bonds with superbases are known and a compilation of them is reported in Table 1. Ethylene itself has been deprotonated by the superbasic mixture constituted by butyllithium, potassium tert-butoxide, and TMEDA.41... 

The reactions of the pyrroles 632 with l-aroyl-2-phenyl ethynes 635 (R = Ph, 2-furyl) in the superbase KOH/DMSO system afforded a mixture of N- 637 ((E)- and (Z)-isomers) and C- 638 ((Z)-isomers) adducts, in a total yield of60-80%, the ratio of the products being dependent on the structure of the starting pyrrole (Equation 151) <2003RJ01195,2003S1272>. 

Isomerization of Alkenes. - Solid superbasic catalysts show remarkable activity in the isomerization of alkenes. At room temperature in the liquid phase the double-bond shift in pent-l-ene and hex-l-ene, and the isomerization of the initially formed 2-alkenes takes place. The highest activity in both types of isomerization is shown by catalysts that have been prepared by deposition of alkali metal by evaporation on MgO calcined below 973 K. In this case the isomerization proceeds on very strong superbasic centres. On MgO-alkali metal calcined at temperatures above 973 K, one-electron donor centres prevail this system causes double bond shift only (Table 7). The superbasic systems are also active in the isomerization of ( )-pent-2-ene to the mixture of (Z)-pent-2-ene and pent-l-ene. The systems for which one-electron donor character prevails are completely inactive in this transformation. 

Brown and Jayaraman [8] have explored the commercially available 9-me-thoxy-9-BBN to capture the carbenoid, (a-chloroallyl)lithium generated in situ. Among the various bases tested for the purpose, lithium dicyclohexylamide (LiNChXj) is the most effective to afford the desired intermediate (3a, Chart 28.1). The dicyclohexylamine liberated is easily removed by precipitation with addition of Mel or Bp3-OEt2. The use of superbase [9], a mixture of (KO-t-Bu and n-BuLi), however, results in tram esterification between the B-OMe and O-f-Bu groups and yield a mixture of 3a and 3c. 

Methylformate decomposition to CO and H2 is effectively catalyzed by solid super-base. The Na —MgO catalyst prepared by heating a mixture of MgO and sodium azide shows much higher activity than MgO alone. Although the basic strength was not measured, the high activity of Na —MgO is considered to be due to superbasicity of the catalyst. 

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