REAGENTS WITH CARBONMETAL BONDS ORGANOMETALLIC SYNTHESIS OF ALCOHOLS

1
Organometallic Compounds
Reagents with Carbon-Metal Bonds
2
FIRST A REVIEW
MAKING CARBON-CARBON BONDS
3
MAKING CARBON-CARBON BONDS
A limited number of methods of making
carbon-carbon bonds exist in organic chemistry.
You have seen several already
SN2 reactions with cyanide and acetylide
Section 12.15
..
..
-
-







..
..
new C-C bond
..
..
-
-





..
..
Section 12.14
new C-C bond
4
MAKING CARBON-CARBON BONDS
Diels-Alder Reaction
Section 14.11

Sections 9.13 14.12
Carbene and carbenoid reactions

5
MAKING CARBON-CARBON BONDS
This chapter introduces a new class of reagents
that are capable of making new carbon-carbon
bonds.
This will allow us to combine small molecular
fragments and build larger molecules from them.
All of these new reagents are
organometallic compounds.
6
CARBON-METAL BONDS
ORGANOMETALLIC COMPOUNDS
R-M R-M-X R-M-R
R is an organic (carbon) group
M is a metal
7
Organometallic Compounds
Alkyl halides (R-X) will react with some metals
to produce organometallic compounds
compounds with a carbon-metal bond
Monovalent Metals ( M Na, Li )
Divalent Metals ( M Mg, Cd)
8
FORMATION OF AN ALKYLLITHIUM COMPOUND
SAMPLE MECHANISM
R-X 2 Li R-Li
LiX
..
These active metals all give up an electron to
the alkyl halide, breaking the C-X bond.
fishhook (one barb) movement of one electron
9
THE SCOPE OF THE REACTIONS
Most halides can be used directly to make an
organometallic lithium or magnesium compound
except alkynyl halides. These can be made, but
special methods (later) are required.
R-X 2 Li R-Li LiX
R-X Mg R-Mg-X
sp3
alkyl halide
or
sp2
vinyl halide
C-X
C-Li
C-MgX
or
sp2
aryl halide
or
sp
X
alkynyl halide
doesnt work directly
discussed later
10
BONDING IN ORGANOMETALLIC
COMPOUNDS
11
ORGANOMETALLIC BONDS
( CARBON-METAL )
carbanion
Carbon-metal bonds are polar bonds that can be
represented by a resonance hybrid of covalent and
ionic structures.
covalent
ionic
12
BASES AND NUCLEOPHILES
All of these reagents react as nucleophiles or
bases, which are bonded to various degrees to the
associated metal.
LEWIS BASE
-
NUCLEOPHILE
electron-pair donor

varying degrees of covalent character depending
on the metal
13
ORGANOMETALLICS FROM MONOVALENT METALS
Na K Li
14
MONOVALENT METALS
Na K
Li
Organosodium and organopotassium reagents are
too reactive to make good organometallic
reagents.
There are problems when trying to form R-Na or
R-K
E2 dehydrohalogenation is an important side
reaction, especially if the alkyl halide is
secondary or tertiary.
SN2 coupling takes place to form dimers.
Both of these problem reactions are shown on the
next slide


Organolithium reagents ( R-Li ) generally work
best.
15
DIFFICULTIES WITH POTASSIUM AND SODIUM
( TOO REACTIVE, R-M IS A STRONG BASE )

ELIMINATION
-
Na
-
COUPLING ( WURTZ REACTION )
Na
In both cases the reagent reacts with the
starting material !
16
SOME EXAMPLES OF THE WURTZ REACTION
If the alkyl halide is a liquid, no solvent is
used.
Na
d
Na
d-
17
PHENYLSODIUM
Phenyl sodium is an exception !
It can be formed without difficulty.

Bromobenzene will not undergo either E2 or
SN2 complications because the bromine is
attatched to an sp2 carbon in the benzene ring,
not to an aliphatic chain.
Phenylsodium has strong ionic character and is
a very strong base.
-


18
ORGANOLITHIUM COMPOUNDS
19
Formation of Organolithium Reagents
R 10, 20, some 30, vinyl and aryl (phenyl)
solvents ethers, pentane, benzene
EXAMPLES
ether

2

pentyllithium


benzene
phenyllithium
20
SOLVENTS THAT ARE FREQUENTLY USED
..
diethyl ether
..
THF tetrahydrofuran
..
..
pentane
These solvents do not react with the
metals themselves or with the organometallic
compounds formed.
benzene
..
..
1,4-dioxane
..
..
21
REACTIONS OF ORGANOLITHIUM
COMPOUNDS
22
REACTIONS OF ORGANOLITHIUM COMPOUNDS
strong base
good nucleophile
significant (-) charge at the carbon
43 ionic
57 covalent
ether
or
R-Li are strong bases and react with acids,
even weak acids like water and alcohols.
CH3- H
strong base
acid
Li
23
The reaction with H2O also means that you must
rigorously exclude water ( and water vapor air
) from your reactions.
24
REMOVING A HALOGEN
The reaction with water is a way of reducing ( or
dehalogenating ) an alkyl halide ( converting C-X
to C-H ) .
ether
Removal of Br
H2O
Li

-
25
MAKING DEUTERIUM COMPOUNDS
ether
Li
Li
ether
Replacing Br with D
D2O
Li
phenyllithium
The reaction of an alkyllithium compound with
water is generally not useful unless you wish to
remove the halogen on the starting compound, or
you use D2O, which is a way of placing a
deuterium atom in your compound.
26
THESE COMPOUNDS CAN BE USED WHEN YOU NEED A VERY
STRONG BASE
When usual bases, such as NaOH or NaOR are not
strong enough, R-Li or Ph-Na can be used.
NaOH

reacts slowly

or
NaOEt
Ph-Na
smooth reaction



or
-
CH3CH2CH2CH2-Li
..
C- is a stronger base than O- since
oxygen is more electronegative and better
accommodates the charge. These are also stronger
bases than NH2- (same reason).
27
YOU MUST EXCLUDE AIR FROM THESE REACTIONS
water vapor (see previous slides), oxygen, and
carbon dioxide react

28
WATER
Water or traces of moisture (water vapor)
destroy the reagent !
R-Li H2O R-H
LiOH
-
-
strong base


Your glassware must be scrupulously dry, and you
must not expose the reagent to humid air.
29
OXYGEN
Oxygen reacts with alkyllithium compounds to
form hydroperoxides.
-


butyllithium
H2O
a hydroperoxide
This reaction usually proceeds in low yield,
meaning it is not a good synthetic method ..
however, it can be a annoying problem when
trying to prepare alkyllithium compounds.
30
CARBON DIOXIDE
Carbon dioxide reacts to make the lithium salts
of carboxylic acids.
R-Li CO2 R-COO- Li
This reaction can be used as an effective
synthetic method ..
discussed in the following slides
31
SYNTHESIS OF CARBOXYLIC ACIDS
32
SYNTHESIS OF CARBOXYLIC ACIDS
Carbon dioxide reacts to form the lithium salt of
a carboxylic acid. This is a good method of
making a carboxylic acid.
-


crushed dry ice
lithium benzoate
phenyllithium
add H3O
For synthesis, solid carbon dioxide (dry ice) is
used.
33
REACTIVITY OF THE CARBONYL GROUP
electrophiles attack here
H or E
nucleophilic at oxygen
..
..
-
d-



d

electrophilic at carbon
Nu
nucleophiles attack here
NUCLEOPHILIC ADDITION
34
REACTIONS WITH THE CARBONYL (CO) GROUP
..
Since oxygen is more electronegative than
carbon, the carbonyl group is electron-deficient
at carbon, that is, it is an electrophile.
d-

d
..
-
Li


-

new C-C bond
The organometallic compound (R-Li) behaves as a
nucleophile with an unshared pair on the carbon.
NUCLEOPHILIC ADDITION TO CARBONYL
35
SYNTHESIS OF A CARBOXYLIC ACID
..

Li
dry-ice
d
ether

..
d-
..

H3O
workup step
-
..


Li
..
CO2
H3O
Li
R-Br R-Li
R-COO- Li R-COOH
usually dil. HCl
36
SYNTHESIS OF ALCOHOLS
Read the following section only from Chap 16
(16.7)
37
SYNTHESIS OF ALCOHOLS
Reaction of RLi with aldeydes and ketones yields
alcohols.

other aldehydes
secondary alcohol

ketones
tertiary alcohol
The type of alcohol depends on whether you use
formaldehyde, another aldehyde, or a ketone.
38
THERE ARE ALWAYS THREE DIFFERENT WAYS TO
SYNTHESIZE AN ALCOHOL
Start with two groups in the carbonyl
compound and add the third.
39
SYNTHESIS PROBLEM
TARGET
Method three, using the other phenyl, is
identical.
METHOD ONE
METHOD TWO
40
USING NaBH4 TO SYNTHESIZE ALCOHOLS
41
SODIUM BOROHYDRIDE IS A HYDRIDE DONOR
_


B
H
B
H
Review also Section 12.13
42
A CARBONYL GROUP IS A SUITABLE ACCEPTOR OF
H- FROM NaBH4
..
..
-
d-
nucleophilic addition



d
-
..
-


The carbon of CO is electron deficient.

43
USING NaBH4 TO SYNTHESIZE ALCOHOLS
H
-
H
C
H
O
H
H
O
2
H
C
H
C
H
3
3
-
H
H
C
H
O
H
O

H
other aldehydes
primary alcohol
C
H
C
H
3
3
-
H
C
O
H

O
H
C
H
C
H
3
3
ketones
secondary alcohol
44
SYNTHESIS PROBLEM
TARGET
METHOD ONE
METHOD TWO
_

What is the third method?
45
SYNTHESIS PROBLEM
MULTISTEP
46
SYNTHESIS PROBLEM
from
47
SYNTHESIS PROBLEM
from