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 , 18711935, 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 (190919)
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!

MgBr
Grignard Reagent

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!

Li

alkyl lithium

Limitations
Cant make Grignards with acidic or electro-philic
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.
Well illustrate this with epoxides.
Recall, acidic protons will kill our reagents and/or
wont 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
- MgBr

OO
THF
THF

Considered
Retrosynthetically:

OH
OH

+
OOMgBr
MgBr HH3OO++
3

Dilute
Dilute

OH

MgBr
+

These is an extremely valuable reaction

Worth celebrating!

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

MgBr

New
C-C
bond

Grignard Reagent

Li

New
C-C
bond

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
2CH3 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
doesnt 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-Iododecane

1. Li, pentane
2. CuI

2
diethyl ether
Br
or THF

2-Methyl-1-dodecene

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 +
trans-1-Iodo-1-nonene

CuLi

Lithium
dibutylcopper

diethyl ether
or THF

New
C-C
bond

trans-5-Tridecene

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 (CH2 )4 MgBr

CH3 (CH2) 7

(CH2 ) 12CH3

C C
H
H
(Z)-9-Tricosene
(Muscalure)

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
Styrene oxide
(racemic)

1-Phenyl-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.

FeelingLost?

Fortunately,Dr.IversonwillbebackonMonday!

Meanwhile.

Back to Grignard Reagents

Addition of a Grignard reagent to formaldehyde
followed by H3O+ gives a 1 alcohol
-

CH
2 -MgBr +
CH3CH
3CH2 MgBr

HH
HH
+ H O ++
+ H
3 O
O
MgBr
CH
CC OO
2 C
3
CH3CH
3CH2 C O MgBr
THF
dil.
THF
HH
HH
dil.

HH
+2
+2
Mg
+
CH
CH
C
OH
CH33CH22 C OH + Mg
HH

This sequence (mechanism) is general and important!

Grignard Reactions
-

+
-MgBr +
CH
CH
3
2
CH3CH2 MgBr

+
- MgBr +

CH
OO CC OO
2 C O
CH3CH
3CH2 C O MgBr
THF
THF
OO

HH3OO +
3
dil.
dil.

These are valuable and important reactions

Please add to your card stock!

+2

+2
++Mg
CH
2 CC OH
Mg
CH3CH
CH
OH
3
2
OO

Grignard reagents react with esters

R'

+ OCH3

MgX O

diethyl
ether

R'
R

OCH
3

O + MgX

but species formed is

unstable and dissociates
under the reaction
conditions to form a ketone

Grignard reagents react with esters

R'

+ OCH3

R'

diethyl
ether

O + MgX

MgX O

this ketone then goes on

to react with a second
mole of the Grignard
reagent to give a tertiary
alcohol

OCH
3

CH3OMgX
R

C
O

R'

Example

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

Practice
OH

MgBr
O

MgBr

O
+

The Same Chemistry is seen With Organolithium Reagents

H2C

CHLi +

CH

1. diethyl ether
2. H3O+

CHCH
OH

CH2
(76%)

Practice
O
OH

MgBr
+

C O

Organometallics are one of the classic ways of activating CO2

End of Lecture. Any Questions?