Lithiation reaction

Carbene complexes have also been prepared by transmetallation reactions. Lithiated azoles react with gold chloride compounds and after protonation or alkylation the corresponding dihydro-azol-ylidene compounds, e.g., (381) or (382), are obtained.22 9-2264 Silver salts of benz-imidazol have also been used to obtain carbene derivatives.2265 Mononuclear gold(I) carbene complexes also form when trimeric gold(I) imidazolyl reacts with ethyl chlorocarbonate or ethyl idodate.2266,2267 The treatment of gold halide complexes with 2-lithiated pyridine followed by protonation or alkylation also yields carbene complexes such as (383).2268 Some of these carbene complexes show luminescent properties.2269-2271... 

Clay den et al. [115] have reported the synthesis of spirocyclic p-lactams 176 (Scheme 41) by exo-cyclization of lithiated pyridine and quinoline carboxamides. The reaction of isonicotinamide or chlorinated isonicotinamide 175 with LDA at -40°C with addition of methyl chloroformate led to the formation of spirocyclic p-lactams 176 in good yields. Benzyl chloroformate, benzoyl chloride, methyl triflate can also be used as the effective acylating agents. In these type of reactions, lithiation of /V-benzyl pyridine and quinoline carboxamides to nitrogen provided... 

Poly p-phenylene (104) was expected to have good thermal and oxidative stability as well as electrical conductivity in the oxidized or reduced states. Rehahn et al. reported the first cross-coupling reaction of dihaloarenes 100 and aryldiboronic acids (101) to provide poly (p-phenylenes) (104) [160]. Homologation was achieved via repeating the following sequence of reactions lithiation, boration, and Suzuki coupling [160]. 

In addition to directed aromatic lithiation reactions, lithiation of aromatic methyl groups can also furnish the isoquinolones. Examples of these are the following ... 

The directed metalation reaction—lithiation with n-butyl-lithium of a position ortho to a substituent on an aromatic ring—is described. Aromatic systems in which the reaction has been studied are benzene, thiophene, naphthalene, and ferrocene. A systematic listing of the bond types that can be formed at the site of metalation is provided. Also of interest is the assessment of the relative directing abilities of directing substituents and comments and observations on the mechanism of the reaction. Utility of the reaction is indicated by the results from asymmetric-directed lithiation and the synthesis of heterocycles. 

In an analogue of the Peterson reaction, lithiated 2-(trimethylsilyl-methyl)pyridine (26) reacts with -aromatic aldimines to give -2-alkenyl-pyridines in high yield and with high stereoselectivity (greater than 99.5% E-configuration). Ketimines and aliphatic imines give much lower yields. ... 

There have been a few reports on the simple route to enamidines offerred by the Peterson reaction. Lithiation of a-silyl amidines such as 66 with Bu Li and subsequent Peterson reaction with carbonyl compounds gives the corresponding enamidines 67 (Scheme 2.42) [106,107). The enamidines 67 are converted to the amines by treatment with sodium borohydride in ethanol under slightly acidic conditions. These entire homologation processes can be performed without purification of the enamidine intermediates 67. 

Akhtar et al. [902(a)] were one of the first to describe completely assembled, sealed, solid-state electrochromic devices based on CPs. In one set of devices, the fairly common Li-triflate/Poly(ethylene oxide) (PEO)/acetonitrile formulation for nonaqueous solid electrolytes was used. However, in another set, the unique combination of poly(ethyleneimines) of different MWt and protonic acids such as hydrochloric, sulfuric, phosphoric, acetic and poly(styrene sulfonic) was used. Additionally, the films of the CP, P(ANi), were prepared electrochemically as well as by sublimation, and in one set of devices Fe-tungstate was used as a counter electrode to provide a definitive counter electrode reaction (Lithiation). While cyclabilities to several thousand cycles were claimed, the electrochromic dynamic range and other parameters were fairly poor, as seen in Figs. 20-3. Very rapid switching times have been claimed for many P(ANi)- or P(ANi)-derivative based devices. For example. Ram et al. [902(b)] claimed a 143 ms switching time for liquid-electrolyte devices based on poly(aniline-co-o-anisidine). 

The lithiation of allene can also be carried out with ethyllithium or butyl-lithium in diethyl ether (prepared from the alkyl bromides), using THF as a cosolvent. The salt suspension which is initially present when the solution of alkyllithium is cooled to -50°C or lower has disappeared almost completely when the reaction between allene and alkyllithium is finished. 

C. The mixture was cooled to -70°C and the allene (0.22 mol) was added in 5-10 min while maintaining the temperature between -60 and -70°C. After stirring for an additional 30 min at -60°C the solution was ready for further conversions. In the raetallation with ethyllithium the salts initially present had disappeared almost completely after this period. During the lithiation with commercial butyl-lithium the reaction mixture was continuously homogeneous. The solution of the lithiated allenes should be kept below -60°C and used within a few hours. 

The reaction of lithiated cumulenic ethers with ethylene oxide, trimethyl-chlorosilane and carbonyl compounds shows the same regiosnecificity as does the alkylation. 

Chiral 2-oxazolidones are useful recyclable auxiliaries for carboxylic acids in highly enantioselective aldol type reactions via the boron enolates derived from N-propionyl-2-oxazolidones (D.A. Evans, 1981). Two reagents exhibiting opposite enantioselectivity ate prepared from (S)-valinol and from (lS,2R)-norephedrine by cyclization with COClj or diethyl carbonate and subsequent lithiation and acylation with propionyl chloride at — 78°C. En-olization with dibutylboryl triflate forms the (Z)-enolates (>99% Z) which react with aldehydes at low temperature. The pure (2S,3R) and (2R,3S) acids or methyl esters are isolated in a 70% yield after mild solvolysis. 

The Li compound 588 formed by the ort/io-lithiation of A. A -dimethylaniline reacts with vinyl bromide to give the styrene derivative 589(433]. The 2-phe-nylindole 591 is formed by the coupling of l-methyl-2-indolylmagnesium formed in situ from the indolyllithium 590 and MgBr2, with iodobenzene using dppb[434]. 2-Furyl- and 2-thienyllithium in the presence of MgBr2 react with alkenyl halides[435]. The arylallenes 592 and 1,2,4-alkatrienes are prepared by the coupling reaction of the allenyllithium with aryl or alkenyl halides[436]. 

Propargylic alcohol, after lithiation, reacts with CO2 to generate the lithium carbonate 243, which undergoes oxypalladation. The reaction of allyl chloride yields the cyclic carbonate 244 and PdC. By this reaction hydroxy and allyl groups are introduced into the triple bond to give the o-allyl ketone 245[129]. Also the formation of 248 from the keto alkyne 246 with CO2 via in situ formation of the carbonate 247 is catalyzed by Pd(0)[130]. 

Lithiated indoles can be alkylated with primary or allylic halides and they react with aldehydes and ketones by addition to give hydroxyalkyl derivatives. Table 10.1 gives some examples of such reactions. Entry 13 is an example of a reaction with ethylene oxide which introduces a 2-(2-hydroxyethyl) substituent. Entries 14 and 15 illustrate cases of addition to aromatic ketones in which dehydration occurs during the course of the reaction. It is likely that this process occurs through intramolecular transfer of the phenylsulfonyl group. 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

Poly(phenylene oxide)s undergo many substitution reactions (25). Reactions involving the aromatic rings and the methyl groups of DMPPO include bromination (26), displacement of the resultant bromine with phosphoms or amines (27), lithiation (28), and maleic anhydride grafting (29). Additional reactions at the open 3-position on the ring include nitration, alkylation (30), and amidation with isocyanates (31). 

Methylthiophene is metallated in the 5-position whereas 3-methoxy-, 3-methylthio-, 3-carboxy- and 3-bromo-thiophenes are metallated in the 2-position (80TL5051). Lithiation of tricarbonyl(i7 -N-protected indole)chromium complexes occurs initially at C-2. If this position is trimethylsilylated, subsequent lithiation is at C-7 with minor amounts at C-4 (81CC1260). Tricarbonyl(Tj -l-triisopropylsilylindole)chromium(0) is selectively lithiated at C-4 by n-butyllithium-TMEDA. This offers an attractive intermediate for the preparation of 4-substituted indoles by reaction with electrophiles and deprotection by irradiation (82CC467). 

Isoxazolyl Grignard reagents react normally in that a 4-carboxylic acid or 4-methanol can be obtained by reaction with CO2 or ketones (63AHC(2)365). Lithiation of 3,5-disub-... 

Benzisothiazole is lithiated at the 3-position, which corresponds to the 5-position in the mononuclear series (75JHC877). 4-Methylisothiazole forms the 5-lithio derivative, but the presence of by-products produced in subsequent reactions suggests the possibility of lithi-ation at the 3-position also (72AHC(14)l). 3-Substituted 1,2-benzisothiazoles suffer attack at sulfur and cleavage of the N—S bond (72AHC(14)43, 73SST(2)556). 

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