Editing Organolithium reagent (section)

== Structure ==
Although simple alkyllithium species are often represented as monomer RLi, they exist as aggregates ([[oligomer]]s) or polymers.<ref name=leadstructure /> 
The degree of aggregation depends on the organic substituent and the presence of other ligands.<ref name=Reich>{{cite journal|last=Reich|first=Hans J.|title=Role of Organolithium Aggregates and Mixed Aggregates in Organolithium Mechanisms|journal=Chemical Reviews|year=2013|volume=113|issue=9|pages=7130–7178|doi=10.1021/cr400187u|pmid=23941648}}</ref><ref name=Strohmann /> These structures have been elucidated by a variety of methods, notably <sup>6</sup>Li, <sup>7</sup>Li, and <sup>13</sup>C [[NMR spectroscopy]] and X-ray diffraction analysis.<ref name="analytical"/> [[Computational chemistry]] supports these assignments.<ref name =leadstructure>{{cite book| last1 = Stey |first1 = Thomas |last2 = Stalke |first2 = Dietmar |chapter = Lead structures in lithium organic chemistry|title = PATAI'S Chemistry of Functional Groups.|publisher = John Wiley & Sons, Ltd |year = 2009|isbn = 9780470682531|doi = 10.1002/9780470682531.pat0298}}</ref>

=== Nature of carbon–lithium bond ===
[[File:Allyllithium.svg|thumb|right|150x100px|Delocalized electron density in allyllithium reagents]] 
The relative [[electronegativity|electronegativities]] of carbon and lithium suggest that the C−Li bond will be highly polar.<ref name=gopakomar>
{{cite book| last1 = Jemmis | first1 = E.D.| last2 = Gopakumar | first2 = G. | chapter = Theoretical studies in organolithium chemistry| title = PATAI'S Chemistry of Functional Groups.| publisher = John Wiley & Sons, Ltd | year = 2009| isbn = 9780470682531 | doi = 10.1002/9780470682531.pat0297}}</ref><ref name=streiwieser>{{cite journal| title = Perspectives on Computational Organic Chemistry| author = Streiwieser, A.| journal = J. Org. Chem.| year = 2009| volume = 74| issue = 12| pages = 4433–4446| doi = 10.1021/jo900497s | pmid = 19518150| pmc = 2728082}}</ref><ref name=bickelhaupt>{{cite journal| title = Covalency in Highly Polar Bonds. Structure and Bonding of Methylalkalimetal Oligomers (CH3M)n (M = Li−Rb; n = 1, 4)| author = Bickelhaupt, F. M.| journal = J. Chem. Theory Comput.| year = 2006| volume = 2| issue = 4| pages = 965–980| doi = 10.1021/ct050333s | pmid = 26633056|display-authors=etal}}</ref>
However, certain organolithium compounds possess properties such as solubility in nonpolar solvents that complicate the issue.
<ref name="gopakomar"/> 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.<ref name=streiwieser/><ref name=bickelhaupt/>  One estimate puts the percentage of ionic character of alkyllithium compounds at 80 to 88%.<ref>{{Cite journal|last=Weiss|first=Erwin|date=November 1993|title=Structures of Organo Alkali Metal Complexes and Related Compounds|journal=Angewandte Chemie International Edition in English|language=en|volume=32|issue=11|pages=1501–1523|doi=10.1002/anie.199315013|issn=0570-0833}}</ref>

In allyl lithium compounds, the lithium cation coordinates to the face of the carbon π bond in an η<sup>3</sup> fashion instead of a localized, carbanionic center, thus, allyllithiums are often less aggregated than alkyllithiums.<ref name=Reich /><ref name=Fraenkelallyllithium>
{{cite journal| title = Observation of a Partially Delocalized Allylic Lithium and the Dynamics of Its 1,3 Lithium Sigmatropic Shift| author = Fraenkel, G.|author2=Qiu, Fayang| journal = J. Am. Chem. Soc.| year = 1996| volume = 118| issue = 24| pages = 5828–5829| doi = 10.1021/ja960440j}}</ref> In aryllithium complexes, the lithium cation coordinates to a single carbanion center through a Li−C σ type bond.<ref name=Reich /><ref name=Fraenkel>
{{cite journal| title = The carbon-lithium bond in monomeric arllithium: Dynamics of exchange, relaxation and rotation| author = Fraenkel. G| journal = J. Am. Chem. Soc.| year = 1995| volume = 117| issue = 23| pages = 6300–6307| doi = 10.1021/ja00128a020 |display-authors=etal}}</ref>
{{multiple image| direction = vertical| width = 180 |height = 400| footer = Solid state structures of methyllithium tetramers, ''n-''butyllithium hexamers and polymeric ladder of phenyllithium| image1 = Methyllithium-tetramer-2-3D-balls.png| image2 = Butyllithium-hexamer-from-xtal-3D-balls-A.png| image3 = Phenyllithium-chain-from-xtal-Mercury-3D-balls.png}}

===Solid state structure===
[[File:Building block of alkyllithium aggregates.png|thumb|270px|left|Tetrahedron and octahedron metal cores formed by aggregation of the Li3 triangle - carbanion coordinate complex<ref name=leadstructure />]]

Like other species consisting of polar subunits, organolithium species aggregate.<ref name=Strohmann>{{cite journal|last=Strohmann|first=C|title=Structure Formation Principles and Reactivity of Organolithium Compounds.|journal= Chem. Eur. J.|year=2009|volume=15|issue=14|pages=3320–3334|url=http://onlinelibrary.wiley.com/store/10.1002/chem.200900041/asset/3320_ftp.pdf?v=1&t=hnc3zl4k&s=90cd763c5affe82ca5d8208a75ea074deede3187|doi=10.1002/chem.200900041|pmid=19260001|display-authors=etal}}</ref><ref name=Power>{{cite journal|last=Power|first=P.P|author2=Hope H.|title=Isolation and crystal structures of the halide-free and halide-rich phenyllithium etherate complexes [(PhLi.Et2O)4] and [(PhLi.Et2O)3.LiBr].|journal=Journal of the American Chemical Society|year=1983|volume=105|issue=16|pages=5320–5324|doi=10.1021/ja00354a022}}</ref>
Formation of aggregates is influenced by [[electrostatic]] interactions, the coordination between lithium and surrounding solvent molecules or polar additives, and steric effects.<ref name=Strohmann />

A basic building block toward constructing more complex structures is a carbanionic center interacting with a Li<sub>3</sub> triangle in an η<sup>3</sup>- fashion.<ref name=leadstructure />
In simple alkyllithium reagents, these triangles aggregate to form tetrahedron or octahedron structures. For example, [[methyllithium]], [[ethyllithium]] and [[tert-Butyllithium|''tert''-butyllithium]] all exist in the tetramer [RLi]<sub>4</sub>. 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.<ref name=leadstructure /><ref name=Strohmann />
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|''n''-butyllithium]], isopropyllithium, and cyclohexanyllithium.<ref name=leadstructure />

[[File:dimerliamide.jpg|thumb|250px|left|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.<ref name="Williard, P. G.; Salvino, J. M. 1993 1–3">{{cite journal|author1=Williard, P. G. |author2=Salvino, J. M. |journal=[[Journal of Organic Chemistry]]|year=1993| volume=58|issue=1|pages=1–3|title=Synthesis, isolation, and structure of an LDA-THF complex |doi=10.1021/jo00053a001}}</ref> 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. 
<ref name=Liamides>{{cite book| last1 = Hilmersson | first1 = Goran| last2 = Granander | first2 = Johan | chapter = Structure and dynamics of chiral lithium amides| title = PATAI'S Chemistry of Functional Groups.| publisher = John Wiley & Sons, Ltd | year = 2009| isbn = 9780470682531 | doi = 10.1002/9780470682531.pat0342}}</ref>
For example, LDA exists primarily as dimers in THF.<ref name="Williard, P. G.; Salvino, J. M. 1993 1–3"/> 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]].<ref name=Collumamides>{{cite journal| title = Lithium Diisopropylamide: Solution Kinetics and Implications for Organic Synthesis| author = Collum, D.B.| journal = Angew. Chem. Int. Ed. | year = 2007| volume = 49| issue = 17| pages = 3002–3017| doi = 10.1002/anie.200603038 | pmid = 17387670|display-authors=etal}}</ref>
Another important class of reagents is silyllithiums, extensively used in the synthesis of organometallic complexes and polysilane [[dendrimers]].<ref name=Strohmann /><ref name=lithiosilanes>{{cite journal|title=Lithiosilanes and their application to the synthesis of polysilane dendrimers |author=Sekiguchi, Akira.|journal=Coord. Chem. Rev.|year=2000 |volume=210 |pages=11–45 |doi=10.1016/S0010-8545(00)00315-5 |display-authors=etal}}</ref>
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.<ref name=Strohmann />
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.<ref name=Strohmann />

===Solution structure===
It is possible for organolithium reagents adopt structures in solution that differ from the solid state.<ref name=Reich /><ref name=solutionenolate>{{cite journal| title = Solution Structures of Lithium Enolates, Phenolates, Carboxylates, and Alkoxides in the Presence of N,N,N′,N′-Tetramethylethylenediamine: A Prevalence of Cyclic Dimers| author = Collum, D. B.| journal = J. Org. Chem.| year = 2008| volume = 73| issue = 19| pages = 7743–7747| doi = 10.1021/jo801532d | pmid = 18781812|display-authors=etal| pmc = 2636848}}</ref> 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.<ref name=Reich /> Separate NMR signals can also differentiate the presence of multiple aggregates from a common monomeric unit.<ref name=reich103>{{cite journal| title = Aggregation and reactivity of phenyllithium solutions| author = Reich, H. J.| journal = J. Am. Chem. Soc.| year = 1998| volume = 120| issue = 29| pages = 7201–7210| doi = 10.1021/ja980684z |display-authors=etal}}</ref>

Organolithium compounds bind [[Lewis base]]s such as [[tetrahydrofuran]] (THF), [[diethyl ether]] (Et<sub>2</sub>O), tetramethylethylene diamine (TMEDA) or [[hexamethylphosphoramide]] (HMPA).<ref name=leadstructure /> [[Methyllithium]] is a special case: its tetrameric structure is unaffected by ether or even HMPA.<ref name=Strohmann /> 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.<ref name=McGarrity>{{cite journal| title = High-field proton NMR study of the aggregation and complexation of n-butyllithium in tetrahydrofuran| author = McGarrity, J. F.|author2=Ogle, C.A.| journal = J. Am. Chem. Soc.| year = 1985| volume = 107| issue = 7| pages = 1805–1810| doi = 10.1021/ja00293a001}}</ref> TMEDA can also chelate to the lithium cations in ''n''-butyllithium and form solvated dimers such as [(TMEDA) LiBu-n)]<sub>2</sub>.<ref name=leadstructure /><ref name = Reich /> 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.<ref name =Reich />

{| border="1" class="wikitable"  style="text-align:center; margin-left: auto; margin-right: auto; border: none;"
|+ Solvated alkyllithium aggregate structures<ref name=Reich />
! Alkyl group
! Solvent
! Structure
|-
| rowspan=2 | methyl || THF || tetramer
|-
| ether/HMPA || tetramer
|-
| rowspan=3 | ''n''{{nbh}}butyl || pentane || hexamer
|-
| ether || tetramer
|-
| THF || tetramer-dimer
|-
| ''sec''{{nbh}}butyl || pentane || hexamer-tetramer
|-
| isopropyl || pentane || hexamer-tetramer
|-
| rowspan=2 | ''tert''{{nbh}}butyl || pentane || tetramer
|-
| THF || monomer
|-
| rowspan=2 | phenyl || ether || tetramer-dimer
|-
| ether/HMPA || dimer
|}

===Structure and reactivity===
As the structures of organolithium reagents change according to their chemical environment, so do their reactivity and selectivity.<ref name=Strohmann /><ref name=whatsgoingon>{{cite journal| title = What's going on with these lithium reagents| author = Reich, H. J.| journal = J. Org. Chem.| year = 2012| volume = 77| issue = 13| pages = 5471–5491| doi = 10.1021/jo3005155| pmid = 22594379}}</ref>
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.<ref name=Strohmann44>
{{cite book| last = Wardell| first = J.L. | chapter = Chapter 2| title = Comprehensive Organometallic Chemistry, Vol. 1| edition = 1st| editor = Wilinson, G. |editor2=Stone, F. G. A. |editor3=Abel, E. W.| publisher = Pergamon| location = New York| year = 1982| isbn = 978-0080406084}}</ref> 
However, reaction pathways in which dimer or other oligomers are the reactive species have also been discovered,<ref name=Strohmann24b>{{cite journal| title = Crystal Structures of n-BuLi Adducts with (R,R)-TMCDA and the Consequences for the Deprotonation of Benzene| author = Strohmann, C.|author2=Gessner, V.H.| journal = J. Am. Chem. Soc.| year = 2008| volume = 130| issue = 35| pages = 11719–11725| doi =  10.1021/ja8017187| pmid=18686951}}</ref> and for lithium amides such as LDA, dimer-based reactions are common.<ref name=Collumldareview>{{cite journal| title = Lithium Diisopropylamide: Solution Kinetics and Implications for Organic Synthesis| author = Collum, D. B.| journal = Angew. Chem. Int. Ed.| year = 2007| volume = 46| issue = 17| pages = 3002–3017| doi = 10.1002/anie.200603038 | pmid = 17387670|display-authors=etal}}</ref> 
A series of solution kinetics studies of LDA-mediated reactions suggest that lower aggregates of enolates do not necessarily lead to higher reactivity.<ref name=Collumamides/>

Also, some Lewis bases increase reactivity of organolithium compounds.<ref name=Chalk>{{cite journal|last=Chalk|first=A.J|author2=Hoogeboom, T.J|title=Ring metalation of toluene by butyllithium in the presence of N,N,N′,N′-tetramethylethylenediamine|journal= J. Organomet. Chem.|year=1968|volume=11|pages=615–618|doi=10.1016/0022-328x(68)80091-9}}</ref>
<ref name=Reich2>{{cite journal|last=Reich|first=H.J|author2=Green, D.P|title=Spectroscopic and Reactivity Studies of Lithium Reagent - HMPA Complexes|journal=Journal of the American Chemical Society|year=1989|volume=111|issue=23|pages=8729–8731|doi=10.1021/ja00205a030}}</ref>
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.<ref name=Chalk/><ref name=Reich2/>
For example, TMEDA increases rates and efficiencies in many reactions involving organolithium reagents.<ref name =Strohmann /> Toward alkyllithium reagents, TMEDA functions as a donor ligand, reduces the degree of aggregation,<ref name =leadstructure /> and increases the nucleophilicity of these species.<ref name=Williard>{{cite journal|last=Williard|first=P.G|author2=Nichols, M.A|title=Solid-state structures of n-butyllithium-TMEDA, -THF, and -DME complexes|journal=Journal of the American Chemical Society|year=1993|volume=115|issue=4|pages=1568–1572|doi=10.1021/ja00057a050}}</ref>
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.<ref name=Collumtmedagood>{{cite journal| title = Is N,N,N,N-Tetramethylethylenediamine a Good Ligand for Lithium?| author = Collum, D.B.| journal = Acc. Chem. Res.| year = 1992| volume = 25| issue = 10| pages = 448–454| doi = 10.1021/ar00022a003}}</ref>
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.<ref name=Collumimine>{{cite journal| title = Solvent- and substrate-dependent rates of imine metalations by lithium diisopropylamide: understanding the mechanisms underlying krel| author = Bernstein, M.P.|author2=Collum, D.B.| journal = J. Am. Chem. Soc.| year = 1993| volume = 115| issue = 18| pages = 8008–8010| doi = 10.1021/ja00071a011}}</ref> Also, as opposed to simple alkyllithium compounds, TMEDA does not deaggregate lithio-acetophenolate in THF solution.<ref name=Reich /><ref name=Seebach>{{cite journal|last=Seebach|first=D|title=Structure and Reactivity of Lithium Enolates. From Pinacolone to Selective C-Alkylations of Peptides. Difficulties and Opportunities Afforded by Complex Structures.|journal=Angew. Chem. Int. Ed. |year=1988|volume=27|issue=12|pages=1624–1654|url=http://onlinelibrary.wiley.com/store/10.1002/anie.198816241/asset/198816241_ftp.pdf?v=1&t=hnc87p5u&s=0a5c03a2a79fd94ea5461e768687e4b5fc7d4f3b|doi=10.1002/anie.198816241}}</ref>
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.<ref name=whatsgoingon />