Butyl lithium, metalation

As soon as the receiver containing the methyl 11 thiurn solution has been removed and stoppered, the residual solids in the reaction flask and the filtration apparatus should be rinsed Into another receiver with anhydrous ether under an atmosphere of argon or nitrogen. The ether slurry of solids, which may contain some unchanged lithium metal, should be treated cautiously in a hood with t-butyl alcohol to consume any residual lithium metal before the mixture is discarded. 

The in situ generation of the carbon dioxide adduct of an indole provides sufficient protection and activation of an indole for metalation at C-2 with r-butyl-lithium. The lithium reagent can be quenched with an electrophile, and quenching of the reaction with water releases the carbon dioxide. ... 

The synthesis of the trisubstituted cyclohexane sector 160 commences with the preparation of optically active (/ )-2-cyclohexen-l-ol (199) (see Scheme 49). To accomplish this objective, the decision was made to utilize the powerful catalytic asymmetric reduction process developed by Corey and his colleagues at Harvard.83 Treatment of 2-bromocyclohexenone (196) with BH3 SMe2 in the presence of 5 mol % of oxazaborolidine 197 provides enantiomeri-cally enriched allylic alcohol 198 (99% yield, 96% ee). Reductive cleavage of the C-Br bond in 198 with lithium metal in terf-butyl alcohol and THF then provides optically active (/ )-2-cyclo-hexen-l-ol (199). When the latter substance is treated with wCPBA, a hydroxyl-directed Henbest epoxidation84 takes place to give an epoxy alcohol which can subsequently be protected in the form of a benzyl ether (see 175) under standard conditions. 

There are some indications that the situation described above has been realized, at least partially, in the system styrene-methyl methacrylate polymerized by metallic lithium.29 29b It is known51 that in a 50-50 mixture of styrene and methyl methacrylate radical polymerization yields a product of approximately the same composition as the feed. On the other hand, a product containing only a few per cent of styrene is formed in a polymerization proceeding by an anionic mechanism. Since the polymer obtained in the 50-50 mixture of styrene and methyl methacrylate polymerized with metallic lithium had apparently an intermediate composition, it has been suggested that this is a block polymer obtained in a reaction discussed above. Further evidence favoring this mechanism is provided by the fact that under identical conditions only pure poly-methyl methacrylate is formed if the polymerization is initiated by butyl lithium and not by lithium dispersion. This proves that incorporation of styrene is due to a different initiation and not propagation. 

Co304 with an excess of n-butyl lithium results in further lithiation of the oxide particles, but with a concomitant extrusion of very finely divided transition metal from the rock salt structure. Highly lithiated iron oxide particles are pyrophoric if exposed to air [100]. 

The synthesis of S-phosphonothiazolin-2-one 133 started with 2-bromothiazole 129. Nucleophilic displacement of the 2-bromide proceeded cleanly with hot anhydrous sodium methoxide to give 2-methoxythiazole 130. Low-temperature metalation of 130 with n-butyl lithium occurred selectively at the 5-position (76), and subsequent electrophilic trapping with diethyl chlorophosphate produced the 5-phosphonate 131. Deprotection of 131 was accomplished either stepwise with mild acid to pn uce the thiazolin-2-one intermediate 132, or directly with trimethylsilyl bromide to give the free phosphonic acid 133, which was isolated as its cyclohexylammonium salt. 

The aryl bromides undergo facile metalation with butyl lithium to produce aryllithium derivatives with the expected organometallic activity.9 For example, reaction of lithiated PPO with carbon dioxide produces a carboxylated PPO which exhibits unique blending characteristics18. 

An alternative synthesis of a thermally stable cyclopentadienyl functionalized polymer involved ring bromination of poly(oxy-2,6-diphenyl-l,4-phenylene), followed by lithiation with butyl lithium to produce an aryllithium polymer. Arylation of 2-norbornen-7-one with the metalated polymer yielded the corresponding 2-norbornen-7-ol derivative. Conversion of the 7-ol to 7-chloro followed by treatment with butyl lithium generated the benzyl anion which undergoes a retro Diels-Alder reaction with the evolution of ethylene to produce the desired aryl cyclopentadiene polymer, 6. 

Silicon linker 76 was used for direct loading of aromatic compounds to supports for the assembly of pyridine-based tricyclics (Scheme 39) [87], Following the initial coupling of an aromatic bromide to the resin by halogen/metal exchange in the presence of tert-butyl lithium, a... 

The zinc complex formed with V,V -diphenylformamidinate is structurally analogous to the basic zinc acetate structure, as [Zn4(/i4-0)L6], and the basic beryllium acetate structure. It is prepared by hydrolysis of zinc bis(diphenylformamidinate).184 Mixed metal zinc lithium species were assembled from dimethyl zinc, t-butyl lithium, V.iV -diphenylbenzamidine and molecular oxygen. The amidinate compounds formed are dependent on the solvent and conditions. Zn2Li2 and... 

In recent years, a variety of aryl boronic acids are commercially available, albeit in some cases they may be expensive for large scale purposes. During our work in the mid-1990 s boronic acid (II) was not commercially available and so two different protocols were used to prepare this acid. The first approach involved the transmetallation with n-butyl lithium of aryl bromide (I) and trapping the lithio species generated with trialkyl borate followed by an acid quench. Aryl bromide (I) is easily prepared by reaction of o-bromobenzenesulfonyl chloride with 2-propanol in the presence of pyridine as a base. The second approach was a directed metallation of isopropyl ester of benzene sulfonic acid (VII), to generate the same lithio species and reaction with trialkyl borate. The sulfonyl ester is prepared by reaction of 2-propanol with benzenesulfonyl chloride. From a long-term strategy the latter approach is... 

In this method, Furstner converts N-BOC protected pyrrole to the 2,5-dibromo compound (122) with NBS and this is followed by metalation and carbomethoxylation with t-butyl lithium in THF and subsequent trapping of the metalated species with methyl chloroformate to yield a pyrrole diester (123). Bromination of this diester at positions 3 and 4 with bromine in water followed by Suzuki cross-coupling with 3,4,5-trimethoxyphenyl boronic acid yields the symmetrical tetrasubstituted pyrrole (125). Base-mediated N-alkylation of this pyrrole with 4-methoxyphenethyl bromide produces the key Boger diester (126) and thereby constitutes a relay synthesis of permethyl storniamide A (120). 

Dimethyl sulphide, Me2S (with estimated pKa value as high as 49 in the medium of DMSO) loses proton with alkyl lithium, the idea has been put forward that any type of non-metal atom bonded to a carbon atom will make a proton attached to that carbon atom acidic to be replaced by strong bases like butyl lithium. 

Deprotonation of (cyclobutadiene)Fe(CO)3 with methyl lithium or n-butyl lithium is not possible15, however lithiation is achieved by use of s-butyl lithium247, or by transmetalation of (chloromercurycyclobutadiene)Fe(CO)3. The metalated cyclobutadiene... 

A number of groups have been found to direct and stabilize o-metallation in aromatic systems since Meyers ( ) introduced the oxazolidine group for this purpose. It was reasoned that the imidazolinone group should also serve this purpose. It was gratifying to find that treatment of the pyridyl imidazolinone 22 th 2.2 equivalents of butyl lithium followed by carbon dioxide gave a good yield of the nicotinic acid 14 (R=H). 

As pointed out earlier (Sect. 7.1), alkyl lithium reagents induce metal-hydrogen exchange reactions. This possibility was investigated first by Paddock and coworkers [266,227]. They have found that the anion generated by the reaction of methylphosphazene with n-butyl lithium interacts with electrophiles such... 

In the Suzuki strategy 138 was treated with trityl chloride to afford amine 139 in 84% yield (Scheme 4.29) (Todo et al., 2000). Metal-halogen exchange of 5-bromoisoindoline 139 was achieved using w-butyl lithium at — 65°C to deliver an intermediate organolithium species that was trapped with triisopropylborate to afford the boronic acid upon work-up. Further treatment of the boronic acid with diethanolamine gave diethanolamine boronic ester 140 (Hayashi et al., 2002). Presumably, the diethanolamine boronic ester was formed for stability reasons, as a given diethanolamine boronic ester tends to be less... 

The second problem results from the fact that the azaenolates exist as aggregates or mixed aggregates in ethereal solvents. Cryoscopic measurements established that the azaenolate generated from 4,5-dihydro-4-methoxymethyl-2-methyl-5-phenyloxazole and butyllithium in tetrahydrofuran is a dimer18. When the metalation was performed with butyllithium or tert-butyl-lithium, an aging effect was observed. Thus, the enantiomeric excess on alkylation drops from 43% to 28% and 11 % when the azaenolates generated at — 78 °C were allowed to warm to... 

---