Organometallic
Compounds
Chapter 15
Guest Lecturer: Prof. Jonathan L. Sessler
AWOL!
Organometallic Compounds
• Organometallic compound: a compound that contains
a carbon-metal bond
• In this chapter, we focus on organometallic
compounds of Mg, Li, and Cu
– these classes illustrate the usefulness of
organometallics in modern synthetic organic
chemistry
– they illustrate how the use of organometallics can
bring about transformations that cannot be
accomplished in any other way
– several more recent reactions of organometallic
compounds are discussed in Chapter 24
Organometallic Reagents
The Key Concepts:
Make a carbon negatively
charged/polarlized so it is nucleophilic.
Reaction with electrophilic carbons
can make carbon-carbon bonds.
This is a Big Deal!
The First Organometallic Reagents…
Grignard Reagents
• Discovered by Victor Grignard
in 1900
– Key factors are ethereal solvent
and water-free conditions
• Awarded Nobel Prize in 1912
Victor Grignard
Grignard, Victor , 1871–1935, French chemist. He shared the 1912 Nobel
Prize in Chemistry for his work in organic synthesis based on his discovery
(1900) of the Grignard Reagent. He taught at the Univ. of Nancy (1909–19)
and at the Univ. of Lyons (from 1919 until the end of his career).
Grignard Reagents
• Grignard reagent: an organomagnesium
compound
– prepared by addition of an alkyl, aryl, or alkenyl
(vinylic) halide to Mg metal in diethyl ether or
THF
Br
+ Mg
1-Bromobutane
Br + Mg
Bromobenzene
ether
MgBr
Butylmagnesium bromide
(an alkyl Grignard reagent)
ether
MgBr
Phenylmagnesium
bromide
(an aryl Grignard reagent)
An Alternative to Grignard Reagents are Alkyl Lithiums
Both are prepared from alkyl, vinyl, and aryl halides under anhydrous conditions
dry ether
+
Br
Mgo
n-butyl bromide
MgBr
or
tetrahydrofuran
(THF)
recall: THF =
Grignard Reagent
O
dry ether
Br
n-butyl bromide
+
2 Lio
or
tetrahydrofuran
(THF)
Li
alkyl lithium
+ LiBr
Grignard and Organolithium Reagents
• Given the difference in electronegativity
between carbon and magnesium (lithium),
the C-Mg (C-Li) bond is polar covalent, with
C- and Mg+ ( Li+ )
– Grignard and organolithium reagents behave
like carbanions
• Carbanion: an anion in which carbon has an
unshared pair of electrons and bears a negative
charge


-
-
+
Li
+
MgBr
Grignard Reagent
alkyl lithium
Grignard and Organolithium Reagents
• Carbanion: an anion in which carbon has
an unshared pair of electrons and bears a
negative charge
– Carbanions are strong bases--they are easily
quenched by even very weak acids (water,
alcohols, amines, amides, carboxylic acids,
even terminal alkynes). A limitation to utility!
pKa = ca. 50
+
MgBr
Grignard Reagent
+
- +
OH
pKa = 16
alkane corresponding
to original alkyl halide
+
O- MgBr+
Grignard and Organolithium Reagents
• Carbanion: an anion in which carbon has
an unshared pair of electrons and bears a
negative charge
– Carbanions are strong bases--they are easily
quenched by even very weak acids (water,
alcohols, amines, carboxylic acids, amides,
even terminal alkynes). A limitation to utility!
pKa = ca. 50
+
Li
 - +
NH2
+
alkane corresponding
to original alkyl halide
+
alkyl lithium
pKa = 40
NH- Li+
Limitations
• Can’t make Grignards with acidic or electrophilic functional groups present in the molecule:
•
R2NH
pKa 38-40
Terminal Alkynes
pKa 25
ROH
pKa 16-18
Carbonyls & Nitros
pKa 11-27
Grignard and Organolithium Reagents
• Carbanion: an anion in which carbon has
an unshared pair of electrons and bears a
negative charge
– Carbanions are also great nucleophiles. This is
the reason for their great utility!
• Key Point: Grignard and Organolithium Reagents
• Great nucleophiles that add efficiently to electrophilic
carbons, such as epoxides and carbonyl group of
aldehydes, ketones and esters. However, their basicity
can be a limitation!
• Epoxides illustrate how many common organic
functional groups contain electrophilic carbons
Grignard and Organolithium Reagents
• Carbanions (nucleophiles) can react with
electrophilic carbon centers in favorable cases.
The net result is a carbon-carbon bond--a big deal!
• Grignards and organolithium reagents react with
many oxygen-containing electrophiles, but not with
alkyl halides.
• We’ll illustrate this with epoxides.
• Recall, acidic protons will “kill” our reagents and/or
won’t allow them to be generated in the first place
Grignard reagents react productively with:
formaldehyde to give primary alcohols
aldehydes to give secondary alcohols
ketones to give tertiary alcohols
esters to give tertiary alcohols
CO2 to give acids
epoxides to give primary alcohols
The one we are
choosing for the sake
of initial illustration
Epoxides: The Example We Want to Stress
New
C-C
bond
- MgBr
+
-
O
Considered
Retrosynthetically:
+
OH
O MgBr H O+
3
Dilute
THF
OH
MgBr
+
These is an extremely valuable reaction…
Worth celebrating!
O
Prof. Iverson Would Normally Play His Trumpet Here!
But, he is gone…
Another Kind of Celebration!
• Cost of Attending USC (per year):
$50,000
• Gymnastics, Tumbling and Cheerleading Lessons:
$20,000
• Keeping Hair Just The Right Shade of Blond:
$10,000
• Cheering for the Wrong Team:
Priceless!
Back to Work: A Related Example
Detailed Mechanism Highlighting Retention of Stereochemistry
New
C-C
bond
Key Points to Note:
Attack at least hindered carbon
Mechanism is SN2-like in initial step
Single enantiomeric product
Chiral center not affected by reaction
Relief of ring strain helps drive reaction
H3O+ breaks up initial salt
Two More Examples of Additions to Epoxides
1.
+
MgBr
O
-
New
C-C
bond
+
2. HCl, H2O
OH
Grignard Reagent
1.
+
Li
Organolithium Reagent
O
New
C-C
bond
-
OH
+
H
H
H
H
2. HCl, H2O
Note: Stereochemistry at
epoxide retained in product
Key point: Orientation Matters!
Gilman Reagents
• Lithium diorganocopper reagents, known more
commonly as Gilman reagents
– prepared by treating an alkyl, aryl, or alkenyl
lithium compound with Cu(I) iodide
diethyl ether
2 CH3 CH2 CH2 CH2 Li + CuI
or THF
Butyllithium
Copper(I)
iodide
( CH3 CH2 CH2 CH2 ) 2 Cu - Li
Lithium dibutylcopper
(a Gilman reagent)
+
+ LiI
Gilman Reagents
• Coupling with organohalogen compounds
– form new carbon-carbon bonds by coupling with alkyl and
alkenyl chlorides, bromides, and iodides. (Note that this
doesn’t work with Grignard or organolithium reagents.
THEY ARE TOO BASIC AND DO E2 ELIMINATIONS.)
R'Br + R2 CuLiBr
diethyl ether
or THF
R'-R + RCu + LiBr
•Example
I
1 . Li, pent ane
2 . CuI
2
1-Iod od ecane
d ie th yl ethe r
Br
or THF
2-Methyl-1-dodecen e
CuLi
New
C-C
bond
Gilman Reagents
– coupling with a vinylic halide is stereospecific; the
configuration of the carbon-carbon double bond is
retained
I +
t rans-1-Iodo-1-nonene
2
CuLi
Lithiu m
dib utylcopper
d iethyl eth er
or THF
New
C-C
bond
trans -5-Tridecen e
Gilman Reagents
• A variation on the preparation of a Gilman
reagent is to use a Grignard reagent with a
catalytic amount of a copper(I) salt
CH3 (CH2 ) 7
(CH2 ) 7 CH2 Br
C C
H
H
(Z)-1-Bromo-9-octadecene
+
Cu
THF
+ CH3 ( CH 2 ) 4 MgBr
CH3 (CH2 ) 7
(CH2 ) 1 2 CH3
C C
H
H
(Z)-9-Tricos ene
(Muscalu re)
Gilman Reagents
• Reaction with epoxides
– regioselective ring opening (attack at least
New
hindered carbon)
C-C
O
OH
bond
1 . ( CH2 =CH) 2 CuLi
2 . H2 O, HCl
S tyrene oxide
(racemic)
1-Ph enyl-3-buten-1-ol
(racemic)
Interim Summary of Introduction to
Organometallic Reagents…
Organolithium reagents and Grignard reagents are
very basic but also great nucleophiles. They react
with epoxides at the less hindered site to give a
two-carbon chain extended alcohol. They do not
couple with alkyl-, aryl-, or vinyl halides.
Gilman reagents react with epoxides as do
organolithium reagents and Grignard reagents.
However, they also add to alkyl-, aryl-, and vinyl
halides to make new C-C bonds.
Feeling Lost?
Fortunately, Dr. Iverson will be back on Monday!
Meanwhile….
Back to Grignard Reagents…
• Addition of a Grignard reagent to formaldehyde
followed by H3O+ gives a 1° alcohol
H
H
-
+
CH3CH2 MgBr
C O
H
-
THF
+
CH3CH2 C O MgBr
H
H3O
dil.
+
H
+2
CH3CH2 C OH + Mg
H
• This sequence (mechanism) is general and important!
Grignard Reactions
CH3CH2
+
MgBr
O C O
-
THF
+
CH3CH2 C O MgBr
O
H3O
+
dil.
These are valuable and important reactions…
Please add to your card stock!
+2
CH3CH2 C OH + Mg
O
Grignard reagents react with esters
– R
R'
••
+ OCH
3
••
C
MgX O ••
••
R'
diethyl
ether
R
C
••
OCH3
••
• O • + MgX
• •• •–
but species formed is
unstable and dissociates
under the reaction
conditions to form a ketone
Grignard reagents react with esters
– R
R'
••
+ OCH
3
••
C
R'
diethyl
ether
R
OCH3
••
• O • + MgX
• •• •–
MgX O ••
••
this ketone then goes on
to react with a second
mole of the Grignard
reagent to give a tertiary
alcohol
C
••
–CH3OMgX
R
R'
C
O ••
••
Example
O
2 CH3MgBr + (CH3)2CHCOCH3
1. diethyl ether
2. H3O+
OH
(CH3)2CHCCH3
CH3
(73%)
Two of the groups
attached to the
tertiary carbon
come from the
Grignard reagent
Practice
OH
MgBr
O
+
H
H
Practice
OH
MgBr
O
+
O
MgBr
+
H
H
The Same Chemistry is seen With Organolithium Reagents
O
H2 C
CHLi +
CH
1. diethyl ether
2. H3O+
CHCH
OH
CH2
(76%)
Practice
O
OH
MgBr
+
O C O
Organometallics are one of the classic ways of activating CO2
End of Lecture. Any Questions?