Compound organolithium

Related to solvents for RLi compounds such as tetrahydrofuran is the keeping quality of RLi solutions in THF. Unlike the relative stability of RMgX in THF (which solvent H. Normant has used so effectively) many of the RLi compounds must be handled with particular care in THF to avoid extensive decomposition at moderate temperatures. We later showed that this decomposition or cleavage of THF by reagents such as triphenyl-silyllithium was a procedure of choice for the synthesis of compounds such as S-triphenylsilylbutanol by ring cleavage of the THF. 

At the beginning a comprehensive study was made of solvents, particularly ether. When some theoretical consideration suggested the probable advantages of rec-butyllithium and of tert-butyllithium for reactions such as metalation, we established that such RLi compounds could be made 

It is relevant for comparative purposes to recall here a statement we made (14) more than 30 years ago on an aspect of the industrial uses of organometallic compounds It is doubtful that any other group of organic compounds combines at the same time an astonishingly high utility in the laboratory with an equally low usefulness in the works.  

analytical procedures were developed for the quantitative analysis of organolithium compounds. Fortunately these had the merit for our studies in being convenient, rapid, and not requiring any special apparatus or equipment beyond conventional laboratory glassware. 

Deuterolysis of the organolithium compounds was used to characterize the three deuterated thiazoles corresponding to the three lithium derivatives. 

The reaction of 2.4-dimethylthiazole with butyllithium shows that, in contrast to 2-methylthiazole, the benzyl position (the 2-position) is the most reactive. The effect of the substituent in the 4-position may well be steric 4-r-butyl-2-methylthiazole in the same reaction gives no 5-substituted product (223). 

Reaction of various reagents (CH3I. CjHjI, PhCHO) on the organolithium products obtained by reaction of butyl-lithium with 2-methyl-4-phenylthiazole gives approximately 90% 5-substitution. The increased reactivity of the hydrogen in the 5-position can be explained by the fact that the -r J effect of a 4-methyl group would increase the electron 

2-Benzylthiazole reacts with n-butyllithium to give 2- and 5-substituted products, but as expected from the particular properties of the 2-methyiene group, the proportion of 2-lithium derivatives is much more important (223). 

An isotopic effect (H or D) has been demonstrated when starting from 2-methyl-4-phenylthiazole or from 2-methyl-4-phenyl-5-D-thiazole (224) in the dimerisation reaction. 

The method now most often used for preparing organolithium compounds is to treat metallic lithium with the appropriate organic halides  

It was Ziegler and Colonius who first showed that the primary products in a Wurtz synthesis are organoalkali compounds which, under suitable conditions, do not react further and can be obtained as the main product of the reaction.34 

Gilman and his co-workers prepared a large number of organolithium compounds by this method.35 An analogous reaction occurs with chloro ethers, yielding, e.g., from chloromethyl ether and lithium in methylal at —25° to —30° (methoxymethyl)lithium, which is stable for days at —70° but decomposes in a few hours at 0°.36 

The course of the reaction is greatly influenced by the nature of the halide and the solvent used. Also, the ease with which it occurs depends appreciably on the sodium content of the lithium 37 direct synthesis of vinyllithium, for instance, is impossible unless the lithium contains sodium (Na content about 2%).38 

Iodides, except methyl iodide, cannot be used because they undergo the Wurtz reaction too easily and thus give low yields of the organolithium compound. In the aliphatic series it is best to use chlorides, and in the aromatic series bromides. It is important that the halide be very pure. 

trans-l,2-dilithioethene o 2, 1,3-dilithiopropane 3, and hexalithio-methane 2.83 4 controversy centered on the explanation for the geometries of these structures. 

Schleyer and his co-workers initially argued that the carbon-lithium bond was primarily covalent. - The Li 2p orbitals could overlap in either a a or IT fashion with the carbon orbitals to form the unusual bridging bonds. For example, in allyllithium, the HOMO of the allyl anion will interact with the lithium 2p orbital as shown in 5. 

These arguments rested heavily on the results of the Mulliken population analysis. The Mulliken charge on Li for a variety of organolithium compounds ranges from about -fO.l to +0.5 (see Tables 23 and 24). Apparently, only partial transfer of charge occurs from lithium to carbon. The overlap population between carbon and lithium is large. For example, the overlap population between Cl and Li in allyllithium is +0.300. In 1,2-dilithioethene, where the 

547 and 0.247, respectively. Breaking this down to individual atomic orbital overlaps, in vinyllithium and 1,2-dilithioethene, the C(2p)—Li(2p) overlaps are 0.070 and 0.079, respectively. The definite sharing of electrons between carbon and lithium, confirmed by the large overlap populations, along with the small charge transfers indicated a primarily covalent C—Li bond. 

On the other hand, Streitwieser argued that the bond is primarily ionic. His argument rested on the IPP charges. The IPP charge on lithium in CH3Li, planar CH2Li2, and tetrahedral CH2Li2 is +0.84, +0.79, and +0.82, respectively. ° 

Submitted by JOHANN T. B. H. JASTRZEBSKI and GERARD VAN KOTEN Checked by M. F. LAPPERT,f P. C. BLAKE/ and D. R. HANKEY  

We describe here a series of organolithium compounds that can be prepared easily as pure crystalline solids. The synthesis involves a heteroatom assisted lithiation reaction6 of the parent hydrocarbon using butyllithium and can, moreover, be scaled up without difficulty. 

Under an inert atmosphere these extremely air-sensitive compounds are, in contrast to their solutions, almost indefinitely stable. The recording of 

The organolithium compounds described here have proved to be valuable in the synthesis of a wide range of cyclometallated compounds, many of which are of current interest.7 The precise site of lithiation in these reagents has been determined from investigations of the air-stable products that they form with Me3SiCl and Me3SnCl.8 

The following detailed procedure is appropriate for the preparation and isolation of all the organolithium compounds on a 25-mmol scale. Precise information concerning reaction times, temperatures, quantity of reagents, and so on is given later for each specific synthesis. 

The bis(propynyl)beryllium compound [Be(C=CMe)2NMe3]2 is unusual in crystallizing with two types of dimeric molecule in the lattice, one of which has a diamond-shaped (Be-C)2 ring very similar to that of 31. The other, structure 32, has a nearly rectangular (Be-C)2 ring, explicable in terms of donation of charge from the alkynyl triple bond into the available metal orbital. 

Rather less symmetrical tetrameric (LiEt)4 molecules have been found (by X-ray diffraction ) in crystalline ethyUithium, again held together by hypercoordinate carbon atoms forming four-center bonds to three neighboring metal atoms located 2.19-2.47 A distant. The Li—Li distances range from 2.42 to 2.63 A and the Li-C-Li angles range from 66° to 67°. 

Methylsodium (NaMe) is believed, on the basis of an X-ray study of the powder, to have a tetrameric structure like that of (LiMe)4. The more electropositive alkali metals form essentially ionic alkyls M (C H2 +i) in which the carbanionic carbon atoms are presumed to be pyramidally coordinated, like the nitrogen atoms of isoelectronic neutral amines NC iH2 +i. 5 

as in (LiMe)4 (34), the hypercoordinate carbon atom forms three normal two-center bonds within the alkyl group and one multicenter bond to the bridged metal atoms. The molecules of benzene of crystallization are located over the equilateral triangular faces of the Lig antiprism. 

It is worth noting that trimethylsilyllithium (LiSiMes) also crystallizes as the hexamer (LiSiMe3)6 based on a Lie trigonal antiprism like that in (cyclohexylLi)6, held together by pg-trimethylsilyl groups in which the silicon atoms are effectively hypercoordinate, forming three normal two-center Si-C bonds and one four-center SiLig bond. 

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CH3)2N]3P0. M.p. 4°C, b.p. 232"C, dielectric constant 30 at 25 C. Can be prepared from dimethylamine and phosphorus oxychloride. Used as an aprotic solvent, similar to liquid ammonia in solvent power but easier to handle. Solvent for organolithium compounds, Grignard reagents and the metals lithium, sodium and potassium (the latter metals give blue solutions). 

It is sometimes necessary e.g., in reactions involving organolithium compounds or in certain Grignard preparations) to carry out a reaction... 

Many organolithium compounds may be prepared by the interaction of lithium with an alkyl chloride or bromide or with an aryl bromide in dry ethereal solution In a nitrogen atmosphere ... 

Another example illustrating the greater reactivity of organolithium compounds is the preparation of the otherwise difficultly accessible esters of 2-pyridyl-acetlc acid by the following series of reactions from a-picoline ... 

Many organic halides do not react satisfactorily with lithium to form RLi ecMnpounds or with metallic magnesium to form Grignard reagents. The desired organolithium compound can often be prepared by a halogen-metal interconversion reaction ... 

The reactions of organolithium compounds with carbonyl compounds, including carbon dioxide, may be interpreted as follows ... 

As pointed out in Note 1 a nitrogen atmosphere is preferred for the preparation of organolithium compounds. In the present example exclusion of oxygen is attained fairly satisfactorily by keeping the solution at the reflux point throughout an atmosphere of ether vapour is thus maintained. 

The most general synthetic route to ketones uses the reaction of carboxylic acids (or their derivatives) or nitriles with organometallic compounds (M.J. Jorgenson, 1970). Lithium car-boxylates react with organolithium compounds to give stable gem-diolates, which are decom-... 

Before we describe the applications of organometallic reagents to organic synthesis let us examine their preparation Organolithium compounds and other Group I organometal he compounds are prepared by the reaction of an alkyl halide with the appropriate metal... 

Organozmc reagents are not nearly as reactive toward aldehydes and ketones as Grig nard reagents and organolithium compounds but are intermediates m certain reactions of alkyl halides... 

Organolithium reagents (Section 14 3) Lithi um metal reacts with organic halides to pro duce organolithium compounds The organic halide may be alkyl alkenyl or aryl Iodides react most and fluorides least readily bro mides are used most often Suitable solvents include hexane diethyl ether and tetrahy drofuran... 

Grignard reagents (Section 14 4) Grignard reagents are prepared in a manner similar to that used for organolithium compounds Di ethyl ether and tetrahydrofuran are appro priate solvents... 

Addition of Grignard reagents and organolithium compounds (Sections 14 6-14 7) Aldehydes are converted to secondary alcohols and ketones to tertiary alcohols... 

B. J. Wakefield, The Chemistry of Organolithium Compounds, Pergamon Press, Ehnsford, N.Y., 1974. 

Other Organolithium Compounds. Organoddithium compounds have utiHty in anionic polymerization of butadiene and styrene. The lithium chain ends can then be converted to useflil functional groups, eg, carboxyl, hydroxyl, etc (139). Lewis bases are requHed for solubdity in hydrocarbon solvents. 

Lithium ion is commonly ingested at dosages of 0.5 g/d of lithium carbonate for treatment of bipolar disorders. However, ingestion of higher concentrations (5 g/d of LiCl) can be fatal. As of this writing, lithium ion has not been related to industrial disease. However, lithium hydroxide, either dHectly or formed by hydrolysis of other salts, can cause caustic bums, and skin contact with lithium haHdes can result in skin dehydration. Organolithium compounds are often pyrophoric and requHe special handling (53). 

It has been postulated that the syn TT-ahyl stmcture yields the trans-1 4 polymer, and the anti TT-ahyl stmcture yields the cis-1 4 polymer. Both the syn and anti TT-ahyl stmctures yield 1,2 units. In the formation of 1,2-polybutadiene, it is beheved that the syn TT-ahyl form yields the syndiotactic stmcture, while the anti TT-ahyl form yields the isotactic stmcture. The equihbtium mixture of syn and anti TT-ahyl stmctures yields heterotactic polybutadiene. It has been shown (20—26) that the syndiotactic stereoisomers of 1,2-polybutadiene units can be made with transition-metal catalysts, and the pure 99.99% 1,2-polybutadiene (heterotactic polybutadiene) [26160-98-5] can be made by using organolithium compounds modified with bis-pipetidinoethane (27). At present, the two stereoisomers of 1,2-polybutadiene that are most used commercially are the syndiotactic and the heterotactic stmctures. 

Addition of Grignard reagents and organolithium compounds to the pyridazine ring proceeds as a nucleophilic attack at one of the electron-deficient positions to give initially... 

Addition of phenylmagnesium bromide to phthalazin-l(2//)-one or derivatives like 4-phenylphthalazin-l(2/f)-one, 4-phenylphthalazine-l(2/f)-thione and 2-substituted phthalazin-l(2//)-ones results in the formation of 1,4-diphenylphthalazines, while addition of organolithium compounds to phthalazin-l(2/f)-one gives the 4-substituted derivative. 

Most isothiazoles are lithiated at the 5-position by the action of butyllithium or other organolithium compounds, provided that this position is vacant (65AHC(4)107, 72AHC(14)l, 77SST(4)339). 3-Methyl-4-nitroisothiazole, however, is inert (65AHC(4)107). 2,1-... 

PALLADIUM-CATALYZED REACTION OF ORGANOLITHIUM COMPOUNDS AND ALKENYL HALIDES ... 

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