GROUP 1 COMPOUNDS – SYNTHESIS AND STRUCTURE Lithium reagents generally exhibit lower reactivity. This arises from lithium forming bonds with a greater covalent character compared to the remaining members of the group. (a result of higher charge density) Metal Charge Density (C/mm 3 ) Li + 52 Na + 24 K + 11 Rb + 8 Cs + 6 This difference in charge density allows lithium reagents to remain associated in solution (in some cases even in the gas phase). The other alkali metal akyl compounds have a more carbanionic nature, and thus a higher reactivity.

Preparation of Organolithium Typically, lithium reagents are made from direct reaction with the metal or metallation: metallation

Preparation Organolithium

Preparation of Organolithium Note that the direct method can lead to contamination for halides This can be avoided by using transmetallation: HgR Li  2LiR + Hg

General Reactivity of Organolithium (and many other main group organometallics) Oxidation – the most electropositive (i.e. s-block) are very strong reducing agents. pyrophoric – ignite spontaneously upon contact with air. This is particularly true of electron deficient compounds with electropositive metals Lewis Acidity – electron deficient species Reactivity – B(C 6 H 5 ) 3 + LiC 6 H 5  LiB(C 6 H 5 ) 4 Carbanion character – protonolysis and nucleophilicity

General Reactivity of Organolithium Oxidation – inert atmosphere – glove box or Schlenk ware – Wilhelm Schlenk

General features of Organolithium Generally soluble in hydrocarbons and ether - increased synthetic utility Can be characterized by titration: Perform under nitrogen in a Schlenk tube with approximately 1.0 mL of THF, add ca. 156 mg (1.0 mmol) of menthol, weighed exactly, and ca. 1 mg of 2,2-bipyridine as the indicator. Cool this orange solution to 0 o C. By syringe, add dropwise the alkyllithium solution until the endpoint is reached (i.e. the indicator turns from orange to red-orange). (the MeLi endpoint can be faint!) [RLi] = m m /( x V) where [RLi] is the concentration in mol/L m m is the mass of the menthol (mg) V is the added volume of lithium reagent (mL)

Organolithium Structures Clusters – a result of Lewis acidity Multicentered bonding and covalent In terms of semilocalized bonding – the three 2s orbitals on each face of the Li 4 tetrahedron overlap with one sp 3 hydrid of CH 3 to give a 4-centered, 2-electron bond (4c,2e bond) Weiss & Hencken JOMC 1970, 21, 265.

Organolithium Structures Clusters – a result of Lewis acidity Multicentered bonding and covalent is a common feature of many Li salts. Structures of nBuLi, tBuLi, CyclohexylLi Siemeling JACS 1994, 116, Stuckey JACS 1974, 96, 6048.

Organolithium Structures Lewis Base Coordination

Organolithium Structures In cases where electron-withdrawing ability is high, the lithium becomes very acidic, and can turn to unlikely bases. A prime example of this is the  6 coordination of benzene (through the  -bond torus): Power et al, JACS 1997, 119, Power et al, JACS 1993, 115, On the Li, the empty sp hybrid orbital not involved in bonding  fashion to the aryl ring  bonds with one of the phenyl ring HOMOs. The difficulty in determining this structure lies in the fact that these “ladder” polymers zig-zag in the z-axis, and are not strongly associated to each other. Thus there is a great deal of disorder in this material.

Organolithium Structures Studies of colligative properties and/or 7 Li NMR suggest that dative bonding solvents will break up oligomers in solution. In most cases, increasing the concentration of TMEDA in the solution stabilizes a dimer of the lithium salt. Thus, small concentrations of TMEDA can increase the reactivity of a lithium reagent.

Reactivity of Organolithium Nucleophilicity Both Grignard reagents and lithium reagents act predominantly as nucleophiles:

Reactivity of Organolithium Nucleophilicity nucleophilicity is the ability to react by donating an electron pair. The following example shows the stabilization of one of two resonance structures by nucleophilic attack: Angew. Chem. Int. Ed. 1999, 38(5), 678. R = dicyclohexylamine

Reactivity of Organolithium Addition to a Carbonyl The mechanism of this reaction is unclear, and it is possible for it to be represented by either a nucleophilic attack on carbon, or by a four- centred intermediate. In actuality, it can be either, depending on complex factors:

Reactivity of Organolithium Reduction of a Carbonyl If the R group in the main group organometallic contains a b- hydrogen, it is possible to compete with addition by a reduction mechanism: Overall, there is a hydride transfer, thus reduction. Both addition and reduction are good ways to make lithium alkoxides.

Reactivity of Organolithium Enolisation of a Carbonyl If addition is attempted on a ketone with an  -hydrogen, enolisation is possible: This is more of a problem with organolithium compounds, as they are more basic, and thus more likely to abstract a proton. Also, Claisen self-condensation is a worry here, as is a bunch of other organic chemistry.

Metallation can be assisted by the donor ability of the solvent or by Lewis base additives to the reaction conditions. These stabilize the cation and allow reaction to occur at a faster rate: HCCl 3 + i PrMgCl + HMPA  CCl 3 MgCl + i PrH (low T) PhCCH + ZnEt 2 + HMPA  (PhCC) 2 Zn + 2 EtH Metallation: Metal – Hydrogen Exchange

Radical Anions It is possible to make salts of alkali metals and large aromatic compounds. An electron is transferred from the metal to a  antibonding orbital on the organic to make the salt They are soluble in organic solvents and strongly reducing making them useful reagents Reducing power can be controlled by your choice or aromatic Other salts containing delocalized anions can be prepared by deprotonating appropriate hydrocarbons – The best example of this is the cyclopentadienide (Cp) anion. Very widely used as a ligand in transition metal organometallic chemistry NaCp