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1967, über, adamantan, und, dessen, stellung, substituierte, 575, 1135, cccc19670570, 570, czechoslovak, communications, yamataka, hiroshi, pat0310, ashby, noding, 1979, compound, 4377, jo01338a026, 4371, carey, francis, kindle, springer, 387, 44899, advanced, bailey, facile, alkyn, yllithiums, 3904, 99279, 3901, baskaran, müller, 2010, germany, verlag, gmbh, kgaa, ch1, living, polymerizations, heinz, brandt, wolfgang, nentwig1, nicola, rooney, laflair, ute, wolf, duffy, judit, puskas, gabor, kaszas, mark, drewitt, stephan, glander, rubber, rubbers, 2011, o23_o02, fananas, francisco, sanz, roberto, pat0341, seebach, 1654, 198816241, 1624, pinacolone, peptides, difficulties, opportunities, afforded, bernstein, dependent, metalations, understanding, krel, 8010, ja00071a011, 8008, 454, ar00022a003, 448, nichols, 1572, ja00057a050, 1568, 8731, ja00205a030, 8729, 111, chalk, hoogeboom, 1968, toluene, 618, 0022, 328x, 80091, 615, organomet, gessner, adducts, tmcda, consequences, benzene, 11725, 18686951, ja8017187, 11719, 130, wardell, chapter, wilinson, stone, abel, 1st, pergamon, 0080406084, comprehensive, vol, 2012, going, 5491, 22594379, jo3005155, 5471, mcgarrity, ogle, 1985, field, complexation, 1810, ja00293a001, 1805, 7210, ja980684z, 7201, 7747, 18781812, 2636848, jo801532d, 7743, phenolates, carboxylates, prevalence, sekiguchi, akira, 2000, lithiosilanes, s0010, 8545, 00315, 210, coord, hilmersson, goran, granander, johan, pat0342, salvino, jo00053a001, power, hope, rich, etherate, 5324, ja00354a022, 5320, 105, 1995, arllithium, relaxation, rotation, 6307, ja00128a020, 6300, 117, qiu, fayang, observation, partially, delocalized, sigmatropic, shift, 5829, ja960440j, 5828, weiss, erwin, november, organo, alkali, 1523, 0570, 0833, 199315013, 1501, angewandte, chemie, international, edition, bickelhaupt, covalency, bonding, methylalkalimetal, ch3m, 980, 26633056, ct050333s, 965, theory, comput, streiwieser, 4446, 19518150, 2728082, jo900497s, 4433, perspectives, 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nature of carbon lithium bond 2 2 solid state structure 2 3 solution structure 2 4 structure and reactivity 3 reactivity and applications toggle reactivity and applications subsection 3 1 as nucleophile 3 1 1 carbolithiation reactions 3 1 2 addition to carbonyl compounds 3 1 3 s n 2 type reactions 3 2 as base 3 2 1 metalation 3 2 2 superbases 4 organolithium reagents in asymmetric synthesis toggle organolithium reagents in asymmetric synthesis subsection 4 1 enolate formation 4 2 lithium halogen exchange 4 3 transmetalation 5 preparation toggle preparation subsection 5 1 displacement of a leaving group 5 2 metalation 5 3 transmetalation 5 4 shapiro reaction 6 handling 7 see also 8 further reading 9 references toggle the table of contents organolithium reagent 25 languages العربية বাংলা català čeština deutsch ελληνικά español eesti euskara فارسی suomi français עברית हिन्दी bahasa indonesia italiano 日本語 한국어 nederlands polski português simple english српски srpski українська 中文 edit links article talk english read edit view history tools tools move to sidebar hide actions read edit view history general what links here related changes upload file permanent link page information cite this page get shortened url switch to legacy parser print export download as pdf printable version in other projects wikimedia commons wikidata item appearance move to sidebar hide from wikipedia the free encyclopedia chemical compounds containing c li bonds organolithium reagents are a collection of organolithium compounds that are widely used in organic synthesis and polymer chemistry these reagents are used to transfer the organic group or the lithium atom to diverse substrates usually through nucleophilic addition or simple deprotonation 1 organolithium reagents are used in industry as an initiator for anionic polymerization which leads to the production of various elastomers 2 a sec butyllithium aggregate in which each of the four sec butyl groups is associated with one face of the tetrahedron formed from four lithium atoms history and development edit studies of organolithium reagents began in the 1930s and were pioneered by karl ziegler georg wittig and henry gilman in comparison with grignard magnesium reagents organolithium reagents can often perform the same reactions with increased rates and higher yields such as in the case of metalation 3 since then organolithium reagents have overtaken grignard reagents in common usage 4 structure edit although simple alkyllithium species are often represented as monomer rli they exist as aggregates oligomers or polymers 5 the degree of aggregation depends on the organic substituent and the presence of other ligands 6 7 these structures have been elucidated by a variety of methods notably 6 li 7 li and 13 c nmr spectroscopy and x ray diffraction analysis 1 computational chemistry supports these assignments 5 nature of carbon lithium bond edit delocalization of electron density in allyllithium reagents due to the large difference in electronegativity between the carbon atom and the lithium atom the c li bond is highly ionic owing to the polar nature of the c li bond organolithium reagents are good nucleophiles and strong bases for laboratory organic synthesis many organolithium reagents are commercially available in solution form these reagents are highly reactive and are sometimes pyrophoric glass bottles containing butyllithium the relative electronegativities of carbon and lithium suggest that the c li bond will be highly polar 8 9 10 however certain organolithium compounds possess properties such as solubility in nonpolar solvents that complicate the issue 8 while most data suggest the c li bond to be essentially ionic there has been debate as to how much covalent character exists in it 9 10 one estimate puts the percentage of ionic character of alkyllithium compounds at 80 to 88 11 in allyl lithium compounds the lithium cation coordinates to the face of the carbon π bond in an η 3 fashion instead of a localized carbanionic center thus allyllithiums are often less aggregated than alkyllithiums 6 12 in aryllithium complexes the lithium cation coordinates to a single carbanion center through a li c σ type bond 6 13 solid state structures of methyllithium tetramers n butyllithium hexamers and polymeric ladder of phenyllithium solid state structure edit tetrahedron and octahedron metal cores formed by aggregation of the li3 triangle carbanion coordinate complex 5 like other species consisting of polar subunits organolithium species aggregate 7 14 formation of aggregates is influenced by electrostatic interactions the coordination between lithium and surrounding solvent molecules or polar additives and steric effects 7 a basic building block toward constructing more complex structures is a carbanionic center interacting with a li 3 triangle in an η 3 fashion 5 in simple alkyllithium reagents these triangles aggregate to form tetrahedron or octahedron structures for example methyllithium ethyllithium and tert butyllithium all exist in the tetramer rli 4 methyllithium exists as tetramers in a cubane type cluster in the solid state with four lithium centers forming a tetrahedron each methanide in the tetramer in methyllithium can have agostic interaction with lithium cations in adjacent tetramers 5 7 ethyllithium and tert butyllithium on the other hand do not exhibit this interaction and are thus soluble in non polar hydrocarbon solvents another class of alkyllithium adopts hexameric structures such as n butyllithium isopropyllithium and cyclohexanyllithium 5 lda dimer with thf coordinated to li cations common lithium amides e g lithium bis trimethylsilyl amide and lithium diisopropylamide are also subject to aggregation 15 lithium amides adopt polymeric ladder type structures in non coordinating solvent in the solid state and they generally exist as dimers in ethereal solvents in the presence of strongly donating ligands tri or tetrameric lithium centers are formed 16 for example lda exists primarily as dimers in thf 15 the structures of common lithium amides such as lithium diisopropylamide lda and lithium hexamethyldisilazide lihmds have been extensively studied by collum and coworkers using nmr spectroscopy 17 another important class of reagents is silyllithiums extensively used in the synthesis of organometallic complexes and polysilane dendrimers 7 18 in the solid state in contrast with alkyllithium reagents most silyllithiums tend to form monomeric structures coordinated with solvent molecules such as thf and only a few silyllithiums have been characterized as higher aggregates 7 this difference can arise from the method of preparation of silyllithiums the steric hindrance caused by the bulky alkyl substituents on silicon and the less polarized nature of si li bonds the addition of strongly donating ligands such as tmeda and sparteine can displace coordinating solvent molecules in silyllithiums 7 solution structure edit it is possible for organolithium reagents adopt structures in solution that differ from the solid state 6 19 nmr spectroscopy has emerged as a powerful tool for the studies of organolithium aggregates in solution for alkyllithium species c li j coupling can often used to determine the number of lithium interacting with a carbanion center and whether these interactions are static or dynamic 6 separate nmr signals can also differentiate the presence of multiple aggregates from a common monomeric unit 20 organolithium compounds bind lewis bases such as tetrahydrofuran thf diethyl ether et 2 o tetramethylethylene diamine tmeda or hexamethylphosphoramide hmpa 5 methyllithium is a special case its tetrameric structure is unaffected by ether or even hmpa 7 on the other hand thf deaggregates hexameric butyl lithium the tetramer is the main species and δg for interconversion between tetramer and dimer is around 11 kcal mol 21 tmeda can also chelate to the lithium cations in n butyllithium and form solvated dimers such as tmeda libu n 2 5 6 phenyllithium has been shown to exist as a distorted tetramer in the crystallized ether solvate and as a mixture of dimer and tetramer in ether solution 6 solvated alkyllithium aggregate structures 6 alkyl group solvent structure methyl thf tetramer ether hmpa tetramer n butyl pentane hexamer ether tetramer thf tetramer dimer sec butyl pentane hexamer tetramer isopropyl pentane hexamer tetramer tert butyl pentane tetramer thf monomer phenyl ether tetramer dimer ether hmpa dimer structure and reactivity edit as the structures of organolithium reagents change according to their chemical environment so do their reactivity and selectivity 7 22 one question surrounding the structure reactivity relationship is whether there exists a correlation between the degree of aggregation and the reactivity of organolithium reagents it was originally proposed that lower aggregates such as monomers are more reactive in alkyllithiums 23 however reaction pathways in which dimer or other oligomers are the reactive species have also been discovered 24 and for lithium amides such as lda dimer based reactions are common 25 a series of solution kinetics studies of lda mediated reactions suggest that lower aggregates of enolates do not necessarily lead to higher reactivity 17 also some lewis bases increase reactivity of organolithium compounds 26 27 however whether these additives function as strong chelating ligands and how the observed increase in reactivity relates to structural changes in aggregates caused by these additives are not always clear 26 27 for example tmeda increases rates and efficiencies in many reactions involving organolithium reagents 7 toward alkyllithium reagents tmeda functions as a donor ligand reduces the degree of aggregation 5 and increases the nucleophilicity of these species 28 however tmeda does not always function as a donor ligand to lithium cation especially in the presence of anionic oxygen and nitrogen centers for example it only weakly interacts with lda and lihmds even in hydrocarbon solvents with no competing donor ligands 29 in imine lithiation while thf acts as a strong donating ligand to lihmds the weakly coordinating tmeda readily dissociates from lihmds leading to the formation of lihmds dimers that is the more reactive species thus in the case of lihmds tmeda does not increase reactivity by reducing aggregation state 30 also as opposed to simple alkyllithium compounds tmeda does not deaggregate lithio acetophenolate in thf solution 6 31 the addition of hmpa to lithium amides such as lihmds and lda often results in a mixture of dimer monomer aggregates in thf however the ratio of dimer monomer species does not change with increased concentration of hmpa thus the observed increase in reactivity is not the result of deaggregation the mechanism of how these additives increase reactivity is still being researched 22 reactivity and applications edit the c li bond in organolithium reagents is highly polarized as a result the carbon attracts most of the electron density in the bond and resembles a carbanion thus organolithium reagents are strongly basic and nucleophilic some of the most common applications of organolithium reagents in synthesis include their use as nucleophiles strong bases for deprotonation initiator for polymerization and starting material for the preparation of other organometallic compounds as nucleophile edit carbolithiation reactions edit as nucleophiles organolithium reagents undergo carbolithiation reactions whereby the carbon lithium bond adds across a carbon carbon double or triple bond forming new organolithium species 32 this reaction is the most widely employed reaction of organolithium compounds carbolithiation is key in anionic polymerization processes and n butyllithium is used as a catalyst to initiate the polymerization of styrene butadiene or isoprene or mixtures thereof 33 34 anionic polymerization of styrene initiated by sec butyllithium another application that takes advantage of this reactivity is the formation of carbocyclic and heterocyclic compounds by intramolecular carbolithiation 32 as a form of anionic cyclization intramolecular carbolithiation reactions offer several advantages over radical cyclization first it is possible for the product cyclic organolithium species to react with electrophiles whereas it is often difficult to trap a radical intermediate of the corresponding structure secondly anionic cyclizations are often more regio and stereospecific than radical cyclization particularly in the case of 5 hexenyllithiums intramolecular carbolithiation allows addition of the alkyl vinyllithium to triple bonds and mono alkyl substituted double bonds aryllithiums can also undergo addition if a 5 membered ring is formed the limitations of intramolecular carbolithiation include difficulty of forming 3 or 4 membered rings as the intermediate cyclic organolithium species often tend to undergo ring openings 32 below is an example of intramolecular carbolithiation reaction the lithium species derived from the lithium halogen exchange cyclized to form the vinyllithium through 5 exo trig ring closure the vinyllithium species further reacts with electrophiles and produce functionalized cyclopentylidene compounds 35 a sample stereoselective intramolecular carbolithiation reaction addition to carbonyl compounds edit nucleophilic organolithium reagents can add to electrophilic carbonyl double bonds to form carbon carbon bonds they can react with aldehydes and ketones to produce alcohols the addition proceeds mainly via polar addition in which the nucleophilic organolithium species attacks from the equatorial direction and produces the axial alcohol 36 addition of lithium salts such as liclo 4 can improve the stereoselectivity of the reaction 37 liclo4 increase selectivity of t buli when the ketone is sterically hindered using grignard reagents often leads to reduction of the carbonyl group instead of addition 36 however alkyllithium reagents are less likely to reduce the ketone and may be used to synthesize substituted alcohols 38 below is an example of ethyllithium addition to adamantone to produce tertiary alcohol 39 li add to adamantone organolithium reagents are also better than grignard reagents in their ability to react with carboxylic acids to form ketones 36 this reaction can be optimized by carefully controlling the amount of organolithium reagent addition or using trimethylsilyl chloride to quench excess lithium reagent 40 a more common way to synthesize ketones is through the addition of organolithium reagents to weinreb amides n methoxy n methyl amides this reaction provides ketones when the organolithium reagents is used in excess due to chelation of the lithium ion between the n methoxy oxygen and the carbonyl oxygen which forms a tetrahedral intermediate that collapses upon acidic work up 41 li add to weinreb organolithium reagents also react with carbon dioxide to form after workup ca...
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