Transcript Nucleophilicity - University of Ottawa

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
Li+
Na+
K+
Rb+
Cs+
Charge Density(C/mm3)
52
24
11
8
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
C5Me5H + nBuLi
C5Me5Li + nBuH
Preparation Organolithium
Preparation of Organolithium
Note that the direct method can lead to contamination for halides
This 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 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 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 acidity
Multicentered bonding and covalent
In 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 Organolithium
Nucleophilicity
Both Grignard reagents and lithium reagents act predominantly as
nucleophiles:
RH
protolysis
H2O
RH
R3COH
HX
R2CO / H2O
oxidation
attack of carbonyl
O2
ROH
RLi
RMgX
RCHO / H2O
EXn
SOCl 2
R2SO
SO 2Cl2
R2SO2
metathesis
ERn
R2CHOH
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:
R2P
C
SiMe3
n
BuLi
-78C
R2P
C
SiMe3
n
R2P
C
SiMe3
Bu Li
R = dicyclohexylamine
Angew. Chem. Int. Ed. 1999, 38(5), 678.
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 fourcentred intermediate.
In actuality, it can be either, depending on complex factors:
R- + M +
RM
M+
O
R
3
C
R2
R-
M
R
R
OM
R
3
C
R
R2
M = Li, MgX
3
O
C
R2
Reactivity of Organolithium
Reduction of a Carbonyl
If the R group in the main group organometallic contains a bhydrogen, it is possible to compete with addition by a reduction
mechanism:
M
O
R3 2
R
M
CH2
H
CH2
O
CH2
+
R3 2
R
H
CH2
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 a-hydrogen,
enolisation is possible:
M
O
3
R
M
CR3
O
+
H
C
R2
CR3
R3
H
CR2
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: Metal – Hydrogen Exchange
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:
n
BuLi +
Li.TMEDA
n
BuLi + TMEDA +
+ nBuH
HCCl3 + iPrMgCl + HMPA  CCl3MgCl + iPrH (low T)
PhCCH + ZnEt2 + HMPA  (PhCC)2Zn + 2 EtH
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