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/mm3)Li+ 52Na+ 24K+ 11Rb+ 8Cs+ 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:

C5Me5H + nBuLi C5Me5Li + nBuH

• metallation

Preparation Organolithium

Preparation of Organolithium

Note that the direct method can lead to contamination for halidesThis can be avoided by using transmetallation:

HgR2 + 2 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(C6H5)3 + LiC6H5 LiB(C6H5)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 tubewith 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 0oC. 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] = mm/(156.26 x V) where [RLi] is the concentration in mol/L

mm is the mass of the menthol (mg)V is the added volume of lithium reagent (mL)

Organolithium Structures

Clusters – a result of Lewis acidityMulticentered bonding and covalentIn terms of semilocalized bonding – the three 2s orbitals on each face of the Li4 tetrahedron overlap with one sp3 hydrid of CH3 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, 5507.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, 2850.Power et al, JACS 1993, 115, 11353.  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 7Li 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 OrganolithiumNucleophilicity

Both Grignard reagents and lithium reagents act predominantly as nucleophiles:

RH

R3COH

R2CHOH

ERn

R2SO2

R2SO

ROH

RH

RLiRMgX

H2O

HX

O2

SOCl2

SO2Cl2

EXn

RCHO / H2O

R2CO / H2O

protolysis

oxidation

metathesis

attack of carbonyl

Reactivity of OrganolithiumNucleophilicity

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.

R2P CSiMe3

R2P CSiMe3

nBuLi

-78CR2P C

SiMe3

LinBu

R = dicyclohexylamine

Reactivity of OrganolithiumAddition 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:

C

O

R3 R2

RM R- + M+

R-

M+

C

OM

R3 R2R

M = Li, MgX

C

O

R3 R2

M

R

Reactivity of OrganolithiumReduction 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.

HCH2

CH2

MO

R2R3

HCH2

CH2

MO

R2R3

+

Reactivity of OrganolithiumEnolisation of a Carbonyl

If addition is attempted on a ketone with an -hydrogen, enolisation is possible:

O

CR2

H

CR3

M

R3

O

CR2

H

CR3

M

R3

+

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: nBuLi +

nBuLi + TMEDA +

Li.TMEDA

+ nBuH

HCCl3 + iPrMgCl + HMPA CCl3MgCl + iPrH (low T)

PhCCH + ZnEt2 + HMPA (PhCC)2Zn + 2 EtH

Metallation: Metal – Hydrogen Exchange

Radical AnionsIt 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