7.AN a aldeídos e cetonas QUI02015 3

Esta é uma pré-visualização de arquivo. Entre para ver o arquivo original

02/09/14 
1 
134 
 
Prof. Dr. José Eduardo Damas Martins 
Formação de enaminas 
135 
 
Prof. Dr. José Eduardo Damas Martins 
Enaminas são formadas pela reação de uma 
amina secundária com um aldeído ou cetona 
que possua ao menos um hidrogênio no 
carbono alfa carbonílico (α−C). 
H no α−C 
R1
O
H
N
R2
R2
R1
N
R2 R2
+ H2O
H+
+
Enamina
02/09/14 
2 
136 
 
Prof. Dr. José Eduardo Damas Martins 
Mecanismo 
1− Protonação da carbonila e adição nucleofílica da 
amina 
R1
O
H+
H
N
R2
R2
R1
O
H
+
R1
O NH
R2
R2
H +
137 
 
Prof. Dr. José Eduardo Damas Martins 
2 − Transferência de próton e eliminação de água 
_ H2O
R1
O NH
R2
R2
H+
R1
N
R2 R2
+
R1
O NH
R2
R2
H +
Imínium
02/09/14 
3 
138 
 
Prof. Dr. José Eduardo Damas Martins 
R1
N
R2 R2
+
H H
O
H
R1
N
R2 R2
Enamina
3 − Formação da enamina 
139 
 
Prof. Dr. José Eduardo Damas Martins 
Devido à alta nucleofilia 
das aminas, a catálise 
ácida pode ocorrer em 
etapa posterior à adição 
nucleofílica. 
02/09/14 
4 
140 
 
Prof. Dr. José Eduardo Damas Martins 
Catalisador atuando 
após a AN da amina 
H
N
R2
R2
R1
C
O
R1
O NH
R2
R2
R1
O N
R2
R2
H +
R1
N
R2 R2
+
Imínium
-
R1
O NH
R2
R2
H+
R1
N
R2 R2
H+
Enamina
141 
 
Prof. Dr. José Eduardo Damas Martins 
Secondary amines react with carbonyl compounds to form enamines
Pyrrolidine, a secondary amine, reacts with isobutyraldehyde, under the sort of conditions you
would use to make an imine, to give an enamine.
The mechanism consists of the same steps as those that take place when imines form from pri-
mary amines, up to formation of the iminium ion. This iminium ion has no N–H proton to lose, so
it loses one of the C–H protons next to the C=N to give the enamine. Enamines, like imines, are un-
stable to aqueous acid. We shall return to them in Chapter 21.
Enamines of primary amines, or even of ammonia, also exist, but only in equilibrium with an
imine isomer. The interconversion between imine and enamine is the nitrogen analogue of enoliza-
tion, which is discussed in detail in Chapter 21.
Iminium ions can react as electrophilic intermediates
We made the point above that the difference in reactivity between an iminium ion and an oxonium
ion is that an iminium ion can lose H+ and form an imine or an enamine, while an oxonium ion
reacts as an electrophile. Iminium ions can, however, react as electrophiles provided suitable nucleo-
philes are present. In fact, they are very good electrophiles, and are significantly more reactive than
Amines react with carbonyl compounds 353
!
The name enamine combines ‘ene’
(C=C double bond) and ‘amine’.
N
O
H
N
H
TsOH catalyst
benzene, heat
–H2O (Dean Stark) enamine
94–95% yield
+
O
H
N
O
N
OH
N
H N
H
H
N
OH2
N
H
secondary amine
(pyrrolidine)
enamine
only proton iminium ion 
can lose is this one
±H
•Imines and enamines
• Imines are formed from aldehydes or ketones with primary amines
• Enamines are formed from aldehydes or ketones with secondary amines
• Both require acid catalysis and removal of water
ON
R1
N
R2R1
H2N
R1
N
H
R2R1
cat. H+
–H2O
cat. H+
–H2O
secondary amine
imine
primary amine
enamine
N
CHO
H2N
HN
imine enamine
Enamina 
Mecanismo ? 
02/09/14 
5 
142 
 
Prof. Dr. José Eduardo Damas Martins 
Nomenclatura de 
Enaminas 
143 
 
Prof. Dr. José Eduardo Damas Martins 
Os nomes das enaminas são obtidos 
com base na nomenclatura das aminas. 
N
N
N-1-ciclohexenil-pirrolidina N,N-dimetil-1-ciclopentenil-amina
02/09/14 
6 
144 
 
Prof. Dr. José Eduardo Damas Martins 
Mostre o composto carbonílico e a 
a m i n a q u e f o r m a r a m o s 
compostos abaixo. 
NN
145 
 
Prof. Dr. José Eduardo Damas Martins 
Caráter nucleofílico de enaminas carbon–carbon bonds: the enamine here is the one derived from cyclohexanone and pyrrolidine.
The product is at first not a carbonyl compound: it’s an iminium ion or an enamine (depending on
whether an appropriate proton can be lost). But a mild acidic hydrolysis converts the iminium ion or
enamine into the corresponding alkylated carbonyl compound.
The overall process, from carbonyl compound to carbonyl compound, amounts to an enolate
alkylation, but no strong base or enolates are involved so there is no danger of self-condensation.
The example below shows two specific examples of cyclohexanone alkylation using enamines. Note
the relatively high temperatures and long reaction times: enamines are among the most reactive of
neutral nucleophiles, but they are still a lot less nucleophilic than enolates.
The choice of the secondary amine for formation of the enamine is not completely arbitrary even
though it does not end up in the final alkylated product. Simple dialkyl amines can be used but cyclic
amines such as pyrrolidine, piperidine, and morpholine are popular choices as the ring structure makes
both the starting amine and the enamine more nucleophilic (the alkyl groups are ‘tied back’ and can’t
get in the way). The higher boiling points of these amines allow the enamine to be formed by heating.
α-Bromo carbonyl compounds are excellent electrophiles for SN2 reactions because of the rate-
enhancing effect of the carbonyl group (Chapter 17). The protons between the halogen and the car-
bonyl are significantly more acidic than those adjacent to just a carbonyl group and there is a serious
risk of an enolate nucleophile acting as a base. Enamines are only very weakly basic, but react well as
a nucleophile with a-bromo carbonyl compounds, and so are a good choice.
The original ketone here is unsymmetrical, so two enamines are possible. However, the formation
of solely the less substituted enamine is typical. The outcome may be explained as the result of ther-
modynamic control: enamine formation is reversible so the less hindered enamine predominates.
672 26 . Alkylation of enolates
O
N
H
N
R X
N
RH
N
R
N
R X
O
R
enamine
iminium enamine
1.
2. H2O, H+
mechanisms for 
the green steps are 
in Chapter 14
hydrolysis
cat H+
N
OBr1.
MeCN, reflux 13 h
2. H2O, 82 °C
N
OCl
Cl Cl
1.
dioxane, reflux 22 h
2. HCl, H2O, 100 °C
N
H
pyrrolidine
N
H
piperidine
N
H
O
morpholine
O
R
Br
H H
NR2 O
Ph
O
Br
Ph
O
O
R2NH
59% yield
1
2. H2Ocat. H
+
02/09/14 
7 
146 
 
Prof. Dr. José Eduardo Damas Martins 
carbon–carbon bonds: the enamine here is the one derived from cyclohexanone and pyrrolidine.
The product is at first not a carbonyl compound: it’s an iminium ion or an enamine (depending on
whether an appropriate proton can be lost). But a mild acidic hydrolysis converts the iminium ion or
enamine into the corresponding alkylated carbonyl compound.
The overall process, from carbonyl compound to carbonyl compound, amounts to an enolate
alkylation, but no strong base or enolates are involved so there is no danger of self-condensation.
The example below shows two specific examples of cyclohexanone alkylation using enamines. Note
the relatively high temperatures and long reaction times: enamines are among the most reactive of
neutral nucleophiles, but they are still a lot less nucleophilic than enolates.
The choice of the secondary amine for formation of the enamine is not completely arbitrary even
though it does not end up in the final alkylated product. Simple dialkyl amines can be used but cyclic
amines such as pyrrolidine, piperidine, and morpholine are popular choices as
the ring structure makes
both the starting amine and the enamine more nucleophilic (the alkyl groups are ‘tied back’ and can’t
get in the way). The higher boiling points of these amines allow the enamine to be formed by heating.
α-Bromo carbonyl compounds are excellent electrophiles for SN2 reactions because of the rate-
enhancing effect of the carbonyl group (Chapter 17). The protons between the halogen and the car-
bonyl are significantly more acidic than those adjacent to just a carbonyl group and there is a serious
risk of an enolate nucleophile acting as a base. Enamines are only very weakly basic, but react well as
a nucleophile with a-bromo carbonyl compounds, and so are a good choice.
The original ketone here is unsymmetrical, so two enamines are possible. However, the formation
of solely the less substituted enamine is typical. The outcome may be explained as the result of ther-
modynamic control: enamine formation is reversible so the less hindered enamine predominates.
672 26 . Alkylation of enolates
O
N
H
N
R X
N
RH
N
R
N
R X
O
R
enamine
iminium enamine
1.
2. H2O, H+
mechanisms for 
the green steps are 
in Chapter 14
hydrolysis
cat H+
N
OBr1.
MeCN, reflux 13 h
2. H2O, 82 °C
N
OCl
Cl Cl
1.
dioxane, reflux 22 h
2. HCl, H2O, 100 °C
N
H
pyrrolidine
N
H
piperidine
N
H
O
morpholine
O
R
Br
H H
NR2 O
Ph
O
Br
Ph
O
O
R2NH
59% yield
1
2. H2Ocat. H
+
Alfa alquilação via enamina 
To be continued… 
147 
 
Prof. Dr. José Eduardo Damas Martins 
Adição de reagentes 
organometálicos à carbonila 
02/09/14 
8 
148 
 
Prof. Dr. José Eduardo Damas Martins 
Reagentes organometálicos são compostos 
que possuem, pelo menos, uma ligação 
carbono−metal. 
C M
 Organometálico
149 
 
Prof. Dr. José Eduardo Damas Martins 
Devido à polarização da ligação C−M, 
reagentes organometálicos possuem um 
carbono nucleofílico (carbânion) capaz de 
realizar adição à carbonila formando uma 
nova ligação C−C. 
C M
δδ
|µ
02/09/14 
9 
150 
 
Prof. Dr. José Eduardo Damas Martins 
δ
R M
δ
Carbono 
nucleofílico 
C
O
+
R M
C
O R
C
HO R
H3O
M
151 
 
Prof. Dr. José Eduardo Damas Martins 
Os reagentes organometálicos mais utilizados 
são: 
1 − Organolítio R Li
2 − Reagentes de Grinard R MgX
X = Cl, Br, I 
02/09/14 
10 
152 
 
Prof. Dr. José Eduardo Damas Martins 
µµµµµµ
Introduction
In Chapters 2–8 we covered basic chemical concepts, which mostly fall under the headings ‘struc-
ture’ (Chapters 2–4 and 7) and ‘reactivity’ (Chapters 5, 6, and 8). These concepts are the bare bones
supporting all of organic chemistry, and now we shall start to put flesh on these bare bones. In
Chapters 9–23 we will tell you about the most important classes of organic reaction in more detail.
One of the things organic chemists do, for all sorts of reasons, is to make molecules. And making
organic molecules means making C–C bonds. In this chapter we are going to look at one of the most
important ways of making C–C bonds: using organometallics, such as organolithiums and Grignard
reagents, and carbonyl compounds. We will consider reactions such as these.
The organometallic reagents act as nucleophiles towards the electrophilic carbonyl group, and
this is the first thing we need to discuss: why are organometallics nucleophilic? We then move on to,
firstly, how to make organometallics, then to the sort of electrophiles they will react with, and then
finally to the sort of molecules we can make with them.
Organometallic compounds contain a carbon–metal bond
The polarity of a covalent bond between two different elements is determined by electronegativity.
The more electronegative an element is, the more it attracts the electron density in the bond. So the 
9Using organometallic reagentsto make C–C bonds
Connections
Building on:
• Electronegativity and the polarization
of bonds ch4
• Grignard reagents and organolithiums
attack carbonyl groups ch6
• C–H deprotonated by very strong
bases ch8
Arriving at:
• Organometallics: nucleophilic and
often strongly basic
• Making organometallics from halo-
compounds
• Making organometallics by
deprotonating carbon atoms
• Using organometallics to make new
C–C bonds from C=O groups
Looking forward to:
• More about organometallics ch10&
ch48
• More ways to make C–C bonds from
C=O groups ch26–ch29
• Synthesis of molecules ch 25 & ch30
!
You met these types of reactions in
Chapter 6: in this chapter we will be
adding more detail with regard to the
nature of the organometallic reagents
and what sort of molecules can be
made using the reactions.
O
Li
OH
1.
2. H+, H2O new C–C bond
89% yield
O
MgBr
HO
1.
2. H+, H2O new C–C bond
90% yield
H
O Li HO H
1.
2. H+, H2O
new C–C bond
80% yield
H
O
MgCl
HO H
1.
2. H+, H2O
new C–C bond
75% yield
Mecanismo ? 
153 
 
Prof. Dr. José Eduardo Damas Martins 
µµµµµµ
Introduction
In Chapters 2–8 we covered basic chemical concepts, which mostly fall under the headings ‘struc-
ture’ (Chapters 2–4 and 7) and ‘reactivity’ (Chapters 5, 6, and 8). These concepts are the bare bones
supporting all of organic chemistry, and now we shall start to put flesh on these bare bones. In
Chapters 9–23 we will tell you about the most important classes of organic reaction in more detail.
One of the things organic chemists do, for all sorts of reasons, is to make molecules. And making
organic molecules means making C–C bonds. In this chapter we are going to look at one of the most
important ways of making C–C bonds: using organometallics, such as organolithiums and Grignard
reagents, and carbonyl compounds. We will consider reactions such as these.
The organometallic reagents act as nucleophiles towards the electrophilic carbonyl group, and
this is the first thing we need to discuss: why are organometallics nucleophilic? We then move on to,
firstly, how to make organometallics, then to the sort of electrophiles they will react with, and then
finally to the sort of molecules we can make with them.
Organometallic compounds contain a carbon–metal bond
The polarity of a covalent bond between two different elements is determined by electronegativity.
The more electronegative an element is, the more it attracts the electron density in the bond. So the 
9Using organometallic reagentsto make C–C bonds
Connections
Building on:
• Electronegativity and the polarization
of bonds ch4
• Grignard reagents and organolithiums
attack carbonyl groups ch6
• C–H deprotonated by very strong
bases ch8
Arriving at:
• Organometallics: nucleophilic and
often strongly basic
• Making organometallics from halo-
compounds
• Making organometallics by
deprotonating carbon atoms
• Using organometallics to make new
C–C bonds from C=O groups
Looking forward to:
• More about organometallics ch10&
ch48
• More ways to make C–C bonds from
C=O groups ch26–ch29
• Synthesis of molecules ch 25 & ch30
!
You met these types of reactions in
Chapter 6: in this chapter we will be
adding more detail with regard to the
nature of the organometallic reagents
and what sort of molecules can be
made using the reactions.
O
Li
OH
1.
2. H+, H2O new C–C bond
89% yield
O
MgBr
HO
1.
2. H+, H2O new C–C bond
90% yield
H
O Li HO H
1.
2. H+, H2O
new C–C bond
80% yield
H
O
MgCl
HO H
1.
2. H+, H2O
new C–C bond
75% yield
Mecanismo ? 
02/09/14 
11 
154 
 
Prof. Dr. José Eduardo Damas Martins 
µµµµµµ
Introduction
In Chapters 2–8 we covered basic chemical concepts, which mostly fall under the headings ‘struc-
ture’ (Chapters 2–4 and
7) and ‘reactivity’ (Chapters 5, 6, and 8). These concepts are the bare bones
supporting all of organic chemistry, and now we shall start to put flesh on these bare bones. In
Chapters 9–23 we will tell you about the most important classes of organic reaction in more detail.
One of the things organic chemists do, for all sorts of reasons, is to make molecules. And making
organic molecules means making C–C bonds. In this chapter we are going to look at one of the most
important ways of making C–C bonds: using organometallics, such as organolithiums and Grignard
reagents, and carbonyl compounds. We will consider reactions such as these.
The organometallic reagents act as nucleophiles towards the electrophilic carbonyl group, and
this is the first thing we need to discuss: why are organometallics nucleophilic? We then move on to,
firstly, how to make organometallics, then to the sort of electrophiles they will react with, and then
finally to the sort of molecules we can make with them.
Organometallic compounds contain a carbon–metal bond
The polarity of a covalent bond between two different elements is determined by electronegativity.
The more electronegative an element is, the more it attracts the electron density in the bond. So the 
9Using organometallic reagentsto make C–C bonds
Connections
Building on:
• Electronegativity and the polarization
of bonds ch4
• Grignard reagents and organolithiums
attack carbonyl groups ch6
• C–H deprotonated by very strong
bases ch8
Arriving at:
• Organometallics: nucleophilic and
often strongly basic
• Making organometallics from halo-
compounds
• Making organometallics by
deprotonating carbon atoms
• Using organometallics to make new
C–C bonds from C=O groups
Looking forward to:
• More about organometallics ch10&
ch48
• More ways to make C–C bonds from
C=O groups ch26–ch29
• Synthesis of molecules ch 25 & ch30
!
You met these types of reactions in
Chapter 6: in this chapter we will be
adding more detail with regard to the
nature of the organometallic reagents
and what sort of molecules can be
made using the reactions.
O
Li
OH
1.
2. H+, H2O new C–C bond
89% yield
O
MgBr
HO
1.
2. H+, H2O new C–C bond
90% yield
H
O Li HO H
1.
2. H+, H2O
new C–C bond
80% yield
H
O
MgCl
HO H
1.
2. H+, H2O
new C–C bond
75% yieldMecanismo ? 
155 
 
Prof. Dr. José Eduardo Damas Martins 
µµµµµµ
Introduction
In Chapters 2–8 we covered basic chemical concepts, which mostly fall under the headings ‘struc-
ture’ (Chapters 2–4 and 7) and ‘reactivity’ (Chapters 5, 6, and 8). These concepts are the bare bones
supporting all of organic chemistry, and now we shall start to put flesh on these bare bones. In
Chapters 9–23 we will tell you about the most important classes of organic reaction in more detail.
One of the things organic chemists do, for all sorts of reasons, is to make molecules. And making
organic molecules means making C–C bonds. In this chapter we are going to look at one of the most
important ways of making C–C bonds: using organometallics, such as organolithiums and Grignard
reagents, and carbonyl compounds. We will consider reactions such as these.
The organometallic reagents act as nucleophiles towards the electrophilic carbonyl group, and
this is the first thing we need to discuss: why are organometallics nucleophilic? We then move on to,
firstly, how to make organometallics, then to the sort of electrophiles they will react with, and then
finally to the sort of molecules we can make with them.
Organometallic compounds contain a carbon–metal bond
The polarity of a covalent bond between two different elements is determined by electronegativity.
The more electronegative an element is, the more it attracts the electron density in the bond. So the 
9Using organometallic reagentsto make C–C bonds
Connections
Building on:
• Electronegativity and the polarization
of bonds ch4
• Grignard reagents and organolithiums
attack carbonyl groups ch6
• C–H deprotonated by very strong
bases ch8
Arriving at:
• Organometallics: nucleophilic and
often strongly basic
• Making organometallics from halo-
compounds
• Making organometallics by
deprotonating carbon atoms
• Using organometallics to make new
C–C bonds from C=O groups
Looking forward to:
• More about organometallics ch10&
ch48
• More ways to make C–C bonds from
C=O groups ch26–ch29
• Synthesis of molecules ch 25 & ch30
!
You met these types of reactions in
Chapter 6: in this chapter we will be
adding more detail with regard to the
nature of the organometallic reagents
and what sort of molecules can be
made using the reactions.
O
Li
OH
1.
2. H+, H2O new C–C bond
89% yield
O
MgBr
HO
1.
2. H+, H2O new C–C bond
90% yield
H
O Li HO H
1.
2. H+, H2O
new C–C bond
80% yield
H
O
MgCl
HO H
1.
2. H+, H2O
new C–C bond
75% yield
Mecanismo ? 
02/09/14 
12 
156 
 
Prof. Dr. José Eduardo Damas Martins 
Cuidado ! 
Organometálicos reagem violentamente 
com a água 
157 
 
Prof. Dr. José Eduardo Damas Martins 
+R M H
O
H R H + M(OH)X
 Reação rápida e exotérmica 
 Organometálicos também reagem com o 
oxigênio do ar 
02/09/14 
13 
158 
 
Prof. Dr. José Eduardo Damas Martins 
A ligação metal−carbono 
159 
 
Prof. Dr. José Eduardo Damas Martins 
A polaridade de uma ligação covalente entre 
dois elementos diferentes é definida pela 
diferença de eletronegatividade . 
δ
|µ
C M
δ
02/09/14 
14 
160 
 
Prof. Dr. José Eduardo Damas Martins 
greater the difference between the electronegativities, the greater the difference between the attrac-
tion for the bonding electrons, and the more polarized the bond becomes. In the extreme case of
complete polarization, the covalent bond ceases to exist and is replaced by electrostatic attraction
between ions of opposite charge. We discussed this in Chapter 4 (p. 000), where we considered the
extreme cases of bonding in NaF.
When we discussed (in Chapter 6) the electrophilic nature of carbonyl groups we saw that their
reactivity is a direct consequence of the polarization of the carbon–oxygen bond towards the more
electronegative oxygen, making the carbon a site for nucleophilic attack. In organolithium com-
pounds and Grignard reagents the key bond bond is polarized in the opposite direction—towards
carbon—making carbon a nucleophilic centre. This is true for most organometallics because, as you
can see from this edited version of the periodic table, metals (such as Li, Mg, Na, K, Ca, and Al) all
have lower electronegativity than carbon.
The orbital diagram—the kind you met in Chapter 4—represents the C–Li bond in methyl-
lithium in terms of a sum of the atomic orbitals of carbon and lithium. Remember that, the more
210 9 . Using organometallic reagents to make C–C bonds
As an example, let’s take a molecule known as
‘juvenile hormone’. It is a compound that prevents
several species of insects from maturing and can be
used as a means of controlling insect pests. Only very
small amounts of the naturally occurring compound
can be isolated, but it can instead be made in the lab
from simple starting materials. At this stage you need
not worry about how, but we can tell you that, of the
sixteen C–C bonds in the final product, seven were
made by reactions of organometallics, many of them
the sort of reactions we will describe in this chapter.
This is not an isolated example. As further proof, take
this important enzyme inhibitor, closely related to
arachidonic acid which you met in Chapter 7. It has
been made by a succession of C–C bond-forming
reactions using organometallics: eight of the twenty
C–C bonds in the product were formed using
organometallic reactions.
How important
are organometallics for making C–C bonds?
O
CO2Me
Cecropia juvenile hormone
CO2H
an enzyme inhibitor
black bonds made by 
organometallic reactions
C O
H
H
C=O π bond polarized 
towards oxygen
electronegativities
2.5 3.5
nucleophiles 
attack here
C Li
H
H
H
C–Li σ bond polarized 
towards carbon
electronegativities
2.5 1.0
MeLi attacks 
electrophiles here
Pauling electronegativities of selected elements
Li
1.0
Be
1.6
Na
0.9
Mg
1.3
K
0.8
Ca
1.0
Cu
1.9
Zn
1.7
Al
1.6
B
2.0
C
2.5
Si
1.9
N
3.04
P
2.2
Se
2.6
Br
3.0
Cl
3.2
F
4.0
S
2.6
O
3.5
H
2.2
Li C
C Li
H
H
H
carbon 
atom
lithium 
atom
Li
e 
n 
e 
r 
g 
y 2s
sp3
C
σ MO
σ* MO
lithium–carbon 
bond
sp3 sp3 sp3
these three orbitals are 
involved in C–H bonds
orbital diagram for the C–Li bond of MeLi
Eletronegatividade de alguns elementos 
δ
|µ
C M
δ
greater the difference between the electronegativities, the greater the difference between the attrac-
tion for the bonding electrons, and the more polarized the bond becomes. In the extreme case of
complete polarization, the covalent bond ceases to exist and is replaced by electrostatic attraction
between ions of opposite charge. We discussed this in Chapter 4 (p. 000), where we considered the
extreme cases of bonding in NaF.
When we discussed (in Chapter 6) the electrophilic nature of carbonyl groups we saw that their
reactivity is a direct consequence of the polarization of the carbon–oxygen bond towards the more
electronegative oxygen, making the carbon a site for nucleophilic attack. In organolithium com-
pounds and Grignard reagents the key bond bond is polarized in the opposite direction—towards
carbon—making carbon a nucleophilic centre. This is true for most organometallics because, as you
can see from this edited version of the periodic table, metals (such as Li, Mg, Na, K, Ca, and Al) all
have lower electronegativity than carbon.
The orbital diagram—the kind you met in Chapter 4—represents the C–Li bond in methyl-
lithium in terms of a sum of the atomic orbitals of carbon and lithium. Remember that, the more
210 9 . Using organometallic reagents to make C–C bonds
As an example, let’s take a molecule known as
‘juvenile hormone’. It is a compound that prevents
several species of insects from maturing and can be
used as a means of controlling insect pests. Only very
small amounts of the naturally occurring compound
can be isolated, but it can instead be made in the lab
from simple starting materials. At this stage you need
not worry about how, but we can tell you that, of the
sixteen C–C bonds in the final product, seven were
made by reactions of organometallics, many of them
the sort of reactions we will describe in this chapter.
This is not an isolated example. As further proof, take
this important enzyme inhibitor, closely related to
arachidonic acid which you met in Chapter 7. It has
been made by a succession of C–C bond-forming
reactions using organometallics: eight of the twenty
C–C bonds in the product were formed using
organometallic reactions.
How important are organometallics for making C–C bonds?
O
CO2Me
Cecropia juvenile hormone
CO2H
an enzyme inhibitor
black bonds made by 
organometallic reactions
C O
H
H
C=O π bond polarized 
towards oxygen
electronegativities
2.5 3.5
nucleophiles 
attack here
C Li
H
H
H
C–Li σ bond polarized 
towards carbon
electronegativities
2.5 1.0
MeLi attacks 
electrophiles here
Pauling electronegativities of selected elements
Li
1.0
Be
1.6
Na
0.9
Mg
1.3
K
0.8
Ca
1.0
Cu
1.9
Zn
1.7
Al
1.6
B
2.0
C
2.5
Si
1.9
N
3.04
P
2.2
Se
2.6
Br
3.0
Cl
3.2
F
4.0
S
2.6
O
3.5
H
2.2
Li C
C Li
H
H
H
carbon 
atom
lithium 
atom
Li
e 
n 
e 
r 
g 
y 2s
sp3
C
σ MO
σ* MO
lithium–carbon 
bond
sp3 sp3 sp3
these three orbitals are 
involved in C–H bonds
orbital diagram for the C–Li bond of MeLi
161 
 
Prof. Dr. José Eduardo Damas Martins 
greater the difference between the electronegativities, the greater the difference between the attrac-
tion for the bonding electrons, and the more polarized the bond becomes. In the extreme case of
complete polarization, the covalent bond ceases to exist and is replaced by electrostatic attraction
between ions of opposite charge. We discussed this in Chapter 4 (p. 000), where we considered the
extreme cases of bonding in NaF.
When we discussed (in Chapter 6) the electrophilic nature of carbonyl groups we saw that their
reactivity is a direct consequence of the polarization of the carbon–oxygen bond towards the more
electronegative oxygen, making the carbon a site for nucleophilic attack. In organolithium com-
pounds and Grignard reagents the key bond bond is polarized in the opposite direction—towards
carbon—making carbon a nucleophilic centre. This is true for most organometallics because, as you
can see from this edited version of the periodic table, metals (such as Li, Mg, Na, K, Ca, and Al) all
have lower electronegativity than carbon.
The orbital diagram—the kind you met in Chapter 4—represents the C–Li bond in methyl-
lithium in terms of a sum of the atomic orbitals of carbon and lithium. Remember that, the more
210 9 . Using organometallic reagents to make C–C bonds
As an example, let’s take a molecule known as
‘juvenile hormone’. It is a compound that prevents
several species of insects from maturing and can be
used as a means of controlling insect pests. Only very
small amounts of the naturally occurring compound
can be isolated, but it can instead be made in the lab
from simple starting materials. At this stage you need
not worry about how, but we can tell you that, of the
sixteen C–C bonds in the final product, seven were
made by reactions of organometallics, many of them
the sort of reactions we will describe in this chapter.
This is not an isolated example. As further proof, take
this important enzyme inhibitor, closely related to
arachidonic acid which you met in Chapter 7. It has
been made by a succession of C–C bond-forming
reactions using organometallics: eight of the twenty
C–C bonds in the product were formed using
organometallic reactions.
How important are organometallics for making C–C bonds?
O
CO2Me
Cecropia juvenile hormone
CO2H
an enzyme inhibitor
black bonds made by 
organometallic reactions
C O
H
H
C=O π bond polarized 
towards oxygen
electronegativities
2.5 3.5
nucleophiles 
attack here
C Li
H
H
H
C–Li σ bond polarized 
towards carbon
electronegativities
2.5 1.0
MeLi attacks 
electrophiles here
Pauling electronegativities of selected elements
Li
1.0
Be
1.6
Na
0.9
Mg
1.3
K
0.8
Ca
1.0
Cu
1.9
Zn
1.7
Al
1.6
B
2.0
C
2.5
Si
1.9
N
3.04
P
2.2
Se
2.6
Br
3.0
Cl
3.2
F
4.0
S
2.6
O
3.5
H
2.2
Li C
C Li
H
H
H
carbon 
atom
lithium 
atom
Li
e 
n 
e 
r 
g 
y 2s
sp3
C
σ MO
σ* MO
lithium–carbon 
bond
sp3 sp3 sp3
these three orbitals are 
involved in C–H bonds
orbital diagram for the C–Li bond of MeLi
Diagrama de orbital molecular da ligação C−Li na molécula de Me−Li 
Orbitais sp3 do carbono 
m a i s p r ó x i m o s e m 
e n e r g i a d o o r b i t a l 
molecular ligante. 
02/09/14 
15 
162 
 
Prof. Dr. José Eduardo Damas Martins 
C O
C Li
H
H
H
HOMO C Li
LUMO π* carbonila
C
H3C O
163 
 
Prof. Dr. José Eduardo Damas Martins 
electronegative an atom is, the lower in energy its atomic orbitals are (p. 000). The filled C–Li σ
orbital that
arises is closer in energy to the carbon’s sp3 orbital than to the lithium’s 2s orbital, so we
can say that the carbon’s sp3 orbital makes a greater contribution to the C–Li σ bond and that the
C–Li bond has a larger coefficient on carbon. Reactions involving the filled σ orbital will therefore
take place at C rather than Li. The same arguments hold for the C–Mg bond of Grignard reagents.
We can also say that, because the carbon’s sp3 orbital makes a greater contribution to the C–Li σ
bond, the σ bond resembles a filled C sp3 orbital—in other words it resembles a lone pair on carbon. This
is a useful idea because it allows us to
think about the way in which methyl-
lithium reacts—as though it were an
ionic compound Me–Li+—and you
may sometimes see MeLi or MeMgCl
represented in mechanisms as Me–.
Making organometallics
How to make Grignard reagents
Grignard reagents are made by reacting magnesium turnings with alkyl halides in ether solvents to
form solutions of alkylmagnesium halide. Iodides, bromides, and chlorides can be used, as can both
aryl and alkyl halides, though they cannot contain any functional groups that would react with the
Grignard reagent once it is formed. Here are some examples.
The reaction scheme is easy enough to draw, but what is the
mechanism? Overall it involves an insertion of magnesium into the
new carbon–halogen bond. There is also a change in oxidation state
of the magnesium, from Mg(0) to Mg(II). The reaction is therefore
known as an oxidative insertion or oxidative addition, and is a
general process for many metals such as Mg, Li (which we meet
shortly), Cu, and Zn.
The mechanism of the reaction is not completely understood
but a possible (but probably not very accurate) way of writing the
mechanism is shown here: the one thing that is certain is that the
first interaction is between the metal and the halogen atom.
Making organometallics 211
!
You have already met cyanide (p.
000), a carbon nucleophile that
really does have a lone pair on
carbon. Cyanide’s lone pair is
stabilized by being in a lower-
energy sp orbital (rather than sp3)
and by having the electronegative
nitrogen atom triply bonded to the
carbon.
!
Carbon atoms that carry a
negative charge, for example
Me–, are known as carbanions.
R Li R Li
R MgX R MgX
organometallic carbanion metal cation
+
+
reacts as though it were
reacts as though it were
Even though these organometallic compounds are extremely
reactive with water and oxygen, and have to be handled
under an atmosphere of nitrogen or argon, a number have
been studied by X-ray crystallography in the solid state and
by NMR in solution. It turns out that they generally form
complex aggregates with two, four, six, or more molecules
bonded together, often with solvent molecules. In this book
we shall not be concerned with these details, and it will
suffice always to represent organometallic compounds as
simple monomeric structures.
The true structure of organolithiums and Grignard reagents is rather more
complicated!
R X
R Mg X
Mg, Et2O
alkylmagnesium halide
(Grignard reagent)
R can be alkyl 
or aryl
X can be I, Br, 
or Cl
!
Diethyl ether (Et2O) and THF are
the most commonly used
solvents, but you may also meet
others such as dimethoxyethane
(DME) and dioxane.
O
O
O
O
MeO
OMe
common ether solvents
diethyl ether THF
(tetrahydrofuran)
dioxane
DME
(dimethoxyethane)
Br MgBr
Mg, THF
MeI MeMgI
Mg, Et2O
Cl MgCl
Mg, THF
Cl MgCl
Mg, Et2O
O
O
Cl
O
O
MgCl
Mg, THF
I MgI
Mg, Et2O
Cl MgCl
Mg, Et2O
Br
Mg
Br
Mg
magnesium inserts 
into this bond
magnesium(0)
magnesium(II)
oxidative insertion
R X
Mg
R Mg X
Reage como se fosse 
Reage como se fosse 
A carga negativa concentrada no carbono, nos 
permite imaginar uma estrutura iônica para o 
organometálico, no seu modo de reagir. 
02/09/14 
16 
164 
 
Prof. Dr. José Eduardo Damas Martins 
Fazendo organometálicos 
165 
 
Prof. Dr. José Eduardo Damas Martins 
Organolítio R Li
São obtidos através de inserção oxidativa entre 
o Li0 e um haleto de alquila. 
02/09/14 
17 
166 
 
Prof. Dr. José Eduardo Damas Martins 
R X + Li0
THF
R Li + LiX
R =- alquil ou aril
X = Cl, Br, I
Síntese de organolítio… 
Inserção oxidativa 
167 
 
Prof. Dr. José Eduardo Damas Martins 
The reaction takes place not in solution but on the surface of the metal, and how easy it is to make
a Grignard reagent can depend on the state of the surface—how finely divided the metal is, for exam-
ple. Magnesium is usually covered by a thin coating of magnesium oxide, and Grignard formation
generally requires ‘initiation’ to allow the metal to come into contact with the alkyl halide. Initiation
can be accomplished by adding a small amount of iodine or 1,2-diiodoethane, or by using ultra-
sound to dislodge the oxide layer. The ether solvent is essential for Grignard formation because (1)
ethers (unlike, say, alcohols or dichloromethane) will not react with Grignards and, more impor-
tantly, (2) only in ethers are Grignard reagents soluble. In Chapter 5 you saw how triethylamine
forms a complex with the Lewis acid BF3, and much the same happens when an ether meets a metal
ion such as magnesium or lithium: the metals are Lewis-acidic because they have empty orbitals (2p
in the case of Li and 3p in the case of Mg) that can accept the lone pair of the ether.
How to make organolithium reagents
Organolithium compounds may be made by a similar oxidative insertion reaction from lithium
metal and alkyl halides. Each inserting reaction requires two atoms of lithium and generates one
equivalent of lithium halide salt. As with Grignard formation, there is really very little limit on the
types of organolithium that can be made this way.
Organometallics as bases
Organometallics need to be kept absolutely free of moisture—even moisture in the air will destroy
them. The reason is that they react very rapidly and highly exothermically with water to produce
212 9 . Using organometallic reagents to make C–C bonds
R
Mg
X
OO
complex between 
Lewis-acidic metal atom 
and lone pairs of THF
R X
R Li LiX
Li, THF
alkylithium plus lithium halide
R can be alkyl 
or aryl
X can be I, Br 
or Cl
MeCl MeLi + LiCl
Li, Et2O Cl Li
+ LiCl
Li, hexane, 
50 °C
Cl Li
+ LiCl
Li, pentane
Br Li
OMe OMe
+ LiBr
Li, THF
Cl Li + LiCl
Li, THF
Br Li + LiBr
Li, Et2O
Most chemists (unless they were working on a very large
scale) would not usually make the simpler organolithiums
or Grignard reagents by these methods, but would buy
them in bottles from chemical companies (who, of course,
do use these methods). The table lists some of the most
important commercially available organolithiums and
Grignard reagents.
Some Grignard and organolithium reagents are commercially available
Commercially available organometallics
methyllithium (MeLi) methylmagnesium chloride, bromide, and iodide
(MeMgX)
n-butyllithium (n-BuLi or just BuLi) ethylmagnesium bromide (EtMgBr)
sec-butyllithium (sec-BuLi or s-BuLi) butylmagnesium chloride (BuMgCl)
tert-butyllithium (tert-BuLi or t-BuLi) allylmagnesium chloride and bromide 
phenyllithium (PhLi) phenylmagnesium chloride and bromide (PhMgCl or
PhMgBr)
Li
Li
Li
MgX
Síntese de organolítio… 
The reaction takes place not in solution but on the surface of the metal, and how easy it is to make
a Grignard reagent can depend on the state of the surface—how finely divided the metal is, for exam-
ple. Magnesium is usually covered by a thin coating of magnesium oxide, and Grignard formation
generally requires ‘initiation’ to allow the metal to come into contact with the alkyl halide. Initiation
can be accomplished by adding a small amount
of iodine or 1,2-diiodoethane, or by using ultra-
sound to dislodge the oxide layer. The ether solvent is essential for Grignard formation because (1)
ethers (unlike, say, alcohols or dichloromethane) will not react with Grignards and, more impor-
tantly, (2) only in ethers are Grignard reagents soluble. In Chapter 5 you saw how triethylamine
forms a complex with the Lewis acid BF3, and much the same happens when an ether meets a metal
ion such as magnesium or lithium: the metals are Lewis-acidic because they have empty orbitals (2p
in the case of Li and 3p in the case of Mg) that can accept the lone pair of the ether.
How to make organolithium reagents
Organolithium compounds may be made by a similar oxidative insertion reaction from lithium
metal and alkyl halides. Each inserting reaction requires two atoms of lithium and generates one
equivalent of lithium halide salt. As with Grignard formation, there is really very little limit on the
types of organolithium that can be made this way.
Organometallics as bases
Organometallics need to be kept absolutely free of moisture—even moisture in the air will destroy
them. The reason is that they react very rapidly and highly exothermically with water to produce
212 9 . Using organometallic reagents to make C–C bonds
R
Mg
X
OO
complex between 
Lewis-acidic metal atom 
and lone pairs of THF
R X
R Li LiX
Li, THF
alkylithium plus lithium halide
R can be alkyl 
or aryl
X can be I, Br 
or Cl
MeCl MeLi + LiCl
Li, Et2O Cl Li
+ LiCl
Li, hexane, 
50 °C
Cl Li
+ LiCl
Li, pentane
Br Li
OMe OMe
+ LiBr
Li, THF
Cl Li + LiCl
Li, THF
Br Li + LiBr
Li, Et2O
Most chemists (unless they were working on a very large
scale) would not usually make the simpler organolithiums
or Grignard reagents by these methods, but would buy
them in bottles from chemical companies (who, of course,
do use these methods). The table lists some of the most
important commercially available organolithiums and
Grignard reagents.
Some Grignard and organolithium reagents are commercially available
Commercially available organometallics
methyllithium (MeLi) methylmagnesium chloride, bromide, and iodide
(MeMgX)
n-butyllithium (n-BuLi or just BuLi) ethylmagnesium bromide (EtMgBr)
sec-butyllithium (sec-BuLi or s-BuLi) butylmagnesium chloride (BuMgCl)
tert-butyllithium (tert-BuLi or t-BuLi) allylmagnesium chloride and bromide 
phenyllithium (PhLi) phenylmagnesium chloride and bromide (PhMgCl or
PhMgBr)
Li
Li
Li
MgX
02/09/14 
18 
168 
 
Prof. Dr. José Eduardo Damas Martins 
Síntese de organolítio… 
The reaction takes place not in solution but on the surface of the metal, and how easy it is to make
a Grignard reagent can depend on the state of the surface—how finely divided the metal is, for exam-
ple. Magnesium is usually covered by a thin coating of magnesium oxide, and Grignard formation
generally requires ‘initiation’ to allow the metal to come into contact with the alkyl halide. Initiation
can be accomplished by adding a small amount of iodine or 1,2-diiodoethane, or by using ultra-
sound to dislodge the oxide layer. The ether solvent is essential for Grignard formation because (1)
ethers (unlike, say, alcohols or dichloromethane) will not react with Grignards and, more impor-
tantly, (2) only in ethers are Grignard reagents soluble. In Chapter 5 you saw how triethylamine
forms a complex with the Lewis acid BF3, and much the same happens when an ether meets a metal
ion such as magnesium or lithium: the metals are Lewis-acidic because they have empty orbitals (2p
in the case of Li and 3p in the case of Mg) that can accept the lone pair of the ether.
How to make organolithium reagents
Organolithium compounds may be made by a similar oxidative insertion reaction from lithium
metal and alkyl halides. Each inserting reaction requires two atoms of lithium and generates one
equivalent of lithium halide salt. As with Grignard formation, there is really very little limit on the
types of organolithium that can be made this way.
Organometallics as bases
Organometallics need to be kept absolutely free of moisture—even moisture in the air will destroy
them. The reason is that they react very rapidly and highly exothermically with water to produce
212 9 . Using organometallic reagents to make C–C bonds
R
Mg
X
OO
complex between 
Lewis-acidic metal atom 
and lone pairs of THF
R X
R Li LiX
Li, THF
alkylithium plus lithium halide
R can be alkyl 
or aryl
X can be I, Br 
or Cl
MeCl MeLi + LiCl
Li, Et2O Cl Li
+ LiCl
Li, hexane, 
50 °C
Cl Li
+ LiCl
Li, pentane
Br Li
OMe OMe
+ LiBr
Li, THF
Cl Li + LiCl
Li, THF
Br Li + LiBr
Li, Et2O
Most chemists (unless they were working on a very large
scale) would not usually make the simpler organolithiums
or Grignard reagents by these methods, but would buy
them in bottles from chemical companies (who, of course,
do use these methods). The table lists some of the most
important commercially available organolithiums and
Grignard reagents.
Some Grignard and organolithium reagents are commercially available
Commercially available organometallics
methyllithium (MeLi) methylmagnesium chloride, bromide, and iodide
(MeMgX)
n-butyllithium (n-BuLi or just BuLi) ethylmagnesium bromide (EtMgBr)
sec-butyllithium (sec-BuLi or s-BuLi) butylmagnesium chloride (BuMgCl)
tert-butyllithium (tert-BuLi or t-BuLi) allylmagnesium chloride and bromide 
phenyllithium (PhLi) phenylmagnesium chloride and bromide (PhMgCl or
PhMgBr)
Li
Li
Li
MgX
The reaction takes place not in solution but on the surface of the metal, and how easy it is to make
a Grignard reagent can depend on the state of the surface—how finely divided the metal is, for exam-
ple. Magnesium is usually covered by a thin coating of magnesium oxide, and Grignard formation
generally requires ‘initiation’ to allow the metal to come into contact with the alkyl halide. Initiation
can be accomplished by adding a small amount of iodine or 1,2-diiodoethane, or by using ultra-
sound to dislodge the oxide layer. The ether solvent is essential for Grignard formation because (1)
ethers (unlike, say, alcohols or dichloromethane) will not react with Grignards and, more impor-
tantly, (2) only in ethers are Grignard reagents soluble. In Chapter 5 you saw how triethylamine
forms a complex with the Lewis acid BF3, and much the same happens when an ether meets a metal
ion such as magnesium or lithium: the metals are Lewis-acidic because they have empty orbitals (2p
in the case of Li and 3p in the case of Mg) that can accept the lone pair of the ether.
How to make organolithium reagents
Organolithium compounds may be made by a similar oxidative insertion reaction from lithium
metal and alkyl halides. Each inserting reaction requires two atoms of lithium and generates one
equivalent of lithium halide salt. As with Grignard formation, there is really very little limit on the
types of organolithium that can be made this way.
Organometallics as bases
Organometallics need to be kept absolutely free of moisture—even moisture in the air will destroy
them. The reason is that they react very rapidly and highly exothermically with water to produce
212 9 . Using organometallic reagents to make C–C bonds
R
Mg
X
OO
complex between 
Lewis-acidic metal atom 
and lone pairs of THF
R X
R Li LiX
Li, THF
alkylithium plus lithium halide
R can be alkyl 
or aryl
X can be I, Br 
or Cl
MeCl MeLi + LiCl
Li, Et2O Cl Li
+ LiCl
Li, hexane, 
50 °C
Cl Li
+ LiCl
Li, pentane
Br Li
OMe OMe
+ LiBr
Li, THF
Cl Li + LiCl
Li, THF
Br Li + LiBr
Li, Et2O
Most chemists (unless they were working on a very large
scale) would not usually make the simpler organolithiums
or Grignard reagents by these methods, but
would buy
them in bottles from chemical companies (who, of course,
do use these methods). The table lists some of the most
important commercially available organolithiums and
Grignard reagents.
Some Grignard and organolithium reagents are commercially available
Commercially available organometallics
methyllithium (MeLi) methylmagnesium chloride, bromide, and iodide
(MeMgX)
n-butyllithium (n-BuLi or just BuLi) ethylmagnesium bromide (EtMgBr)
sec-butyllithium (sec-BuLi or s-BuLi) butylmagnesium chloride (BuMgCl)
tert-butyllithium (tert-BuLi or t-BuLi) allylmagnesium chloride and bromide 
phenyllithium (PhLi) phenylmagnesium chloride and bromide (PhMgCl or
PhMgBr)
Li
Li
Li
MgX
169 
 
Prof. Dr. José Eduardo Damas Martins 
Reagentes de 
Grinard 
São obtidos através da reação entre o Mg0 e 
um haleto de alquila ou arila em éter seco. 
R MgX
02/09/14 
19 
170 
 
Prof. Dr. José Eduardo Damas Martins 
R X + Mg0
éter seco
R MgX
R =- alquil ou aril
X = Cl, Br, I
δδ
Síntese de reagente de Grinard… 
171 
 
Prof. Dr. José Eduardo Damas Martins 
electronegative an atom is, the lower in energy its atomic orbitals are (p. 000). The filled C–Li σ
orbital that arises is closer in energy to the carbon’s sp3 orbital than to the lithium’s 2s orbital, so we
can say that the carbon’s sp3 orbital makes a greater contribution to the C–Li σ bond and that the
C–Li bond has a larger coefficient on carbon. Reactions involving the filled σ orbital will therefore
take place at C rather than Li. The same arguments hold for the C–Mg bond of Grignard reagents.
We can also say that, because the carbon’s sp3 orbital makes a greater contribution to the C–Li σ
bond, the σ bond resembles a filled C sp3 orbital—in other words it resembles a lone pair on carbon. This
is a useful idea because it allows us to
think about the way in which methyl-
lithium reacts—as though it were an
ionic compound Me–Li+—and you
may sometimes see MeLi or MeMgCl
represented in mechanisms as Me–.
Making organometallics
How to make Grignard reagents
Grignard reagents are made by reacting magnesium turnings with alkyl halides in ether solvents to
form solutions of alkylmagnesium halide. Iodides, bromides, and chlorides can be used, as can both
aryl and alkyl halides, though they cannot contain any functional groups that would react with the
Grignard reagent once it is formed. Here are some examples.
The reaction scheme is easy enough to draw, but what is the
mechanism? Overall it involves an insertion of magnesium into the
new carbon–halogen bond. There is also a change in oxidation state
of the magnesium, from Mg(0) to Mg(II). The reaction is therefore
known as an oxidative insertion or oxidative addition, and is a
general process for many metals such as Mg, Li (which we meet
shortly), Cu, and Zn.
The mechanism of the reaction is not completely understood
but a possible (but probably not very accurate) way of writing the
mechanism is shown here: the one thing that is certain is that the
first interaction is between the metal and the halogen atom.
Making organometallics 211
!
You have already met cyanide (p.
000), a carbon nucleophile that
really does have a lone pair on
carbon. Cyanide’s lone pair is
stabilized by being in a lower-
energy sp orbital (rather than sp3)
and by having the electronegative
nitrogen atom triply bonded to the
carbon.
!
Carbon atoms that carry a
negative charge, for example
Me–, are known as carbanions.
R Li R Li
R MgX R MgX
organometallic carbanion metal cation
+
+
reacts as though it were
reacts as though it were
Even though these organometallic compounds are extremely
reactive with water and oxygen, and have to be handled
under an atmosphere of nitrogen or argon, a number have
been studied by X-ray crystallography in the solid state and
by NMR in solution. It turns out that they generally form
complex aggregates with two, four, six, or more molecules
bonded together, often with solvent molecules. In this book
we shall not be concerned with these details, and it will
suffice always to represent organometallic compounds as
simple monomeric structures.
The true structure of organolithiums and Grignard reagents is rather more
complicated!
R X
R Mg X
Mg, Et2O
alkylmagnesium halide
(Grignard reagent)
R can be alkyl 
or aryl
X can be I, Br, 
or Cl
!
Diethyl ether (Et2O) and THF are
the most commonly used
solvents, but you may also meet
others such as dimethoxyethane
(DME) and dioxane.
O
O
O
O
MeO
OMe
common ether solvents
diethyl ether THF
(tetrahydrofuran)
dioxane
DME
(dimethoxyethane)
Br MgBr
Mg, THF
MeI MeMgI
Mg, Et2O
Cl MgCl
Mg, THF
Cl MgCl
Mg, Et2O
O
O
Cl
O
O
MgCl
Mg, THF
I MgI
Mg, Et2O
Cl MgCl
Mg, Et2O
Br
Mg
Br
Mg
magnesium inserts 
into this bond
magnesium(0)
magnesium(II)
oxidative insertion
R X
Mg
R Mg X
Éteres mais 
 utilizados 
Síntese de reagente de Grinard… 
02/09/14 
20 
172 
 
Prof. Dr. José Eduardo Damas Martins 
electronegative an atom is, the lower in energy its atomic orbitals are (p. 000). The filled C–Li σ
orbital that arises is closer in energy to the carbon’s sp3 orbital than to the lithium’s 2s orbital, so we
can say that the carbon’s sp3 orbital makes a greater contribution to the C–Li σ bond and that the
C–Li bond has a larger coefficient on carbon. Reactions involving the filled σ orbital will therefore
take place at C rather than Li. The same arguments hold for the C–Mg bond of Grignard reagents.
We can also say that, because the carbon’s sp3 orbital makes a greater contribution to the C–Li σ
bond, the σ bond resembles a filled C sp3 orbital—in other words it resembles a lone pair on carbon. This
is a useful idea because it allows us to
think about the way in which methyl-
lithium reacts—as though it were an
ionic compound Me–Li+—and you
may sometimes see MeLi or MeMgCl
represented in mechanisms as Me–.
Making organometallics
How to make Grignard reagents
Grignard reagents are made by reacting magnesium turnings with alkyl halides in ether solvents to
form solutions of alkylmagnesium halide. Iodides, bromides, and chlorides can be used, as can both
aryl and alkyl halides, though they cannot contain any functional groups that would react with the
Grignard reagent once it is formed. Here are some examples.
The reaction scheme is easy enough to draw, but what is the
mechanism? Overall it involves an insertion of magnesium into the
new carbon–halogen bond. There is also a change in oxidation state
of the magnesium, from Mg(0) to Mg(II). The reaction is therefore
known as an oxidative insertion or oxidative addition, and is a
general process for many metals such as Mg, Li (which we meet
shortly), Cu, and Zn.
The mechanism of the reaction is not completely understood
but a possible (but probably not very accurate) way of writing the
mechanism is shown here: the one thing that is certain is that the
first interaction is between the metal and the halogen atom.
Making organometallics 211
!
You have already met cyanide (p.
000), a carbon nucleophile that
really does have a lone pair on
carbon. Cyanide’s lone pair is
stabilized by being in a lower-
energy sp orbital (rather than sp3)
and by having the electronegative
nitrogen atom triply bonded to the
carbon.
!
Carbon atoms that carry a
negative charge, for example
Me–, are known as carbanions.
R Li R Li
R MgX R MgX
organometallic carbanion metal cation
+
+
reacts as though it were
reacts as though it were
Even though these organometallic compounds are extremely
reactive with water and oxygen, and have to be handled
under an atmosphere of nitrogen or argon, a number have
been studied by X-ray crystallography in the solid state and
by
NMR in solution. It turns out that they generally form
complex aggregates with two, four, six, or more molecules
bonded together, often with solvent molecules. In this book
we shall not be concerned with these details, and it will
suffice always to represent organometallic compounds as
simple monomeric structures.
The true structure of organolithiums and Grignard reagents is rather more
complicated!
R X
R Mg X
Mg, Et2O
alkylmagnesium halide
(Grignard reagent)
R can be alkyl 
or aryl
X can be I, Br, 
or Cl
!
Diethyl ether (Et2O) and THF are
the most commonly used
solvents, but you may also meet
others such as dimethoxyethane
(DME) and dioxane.
O
O
O
O
MeO
OMe
common ether solvents
diethyl ether THF
(tetrahydrofuran)
dioxane
DME
(dimethoxyethane)
Br MgBr
Mg, THF
MeI MeMgI
Mg, Et2O
Cl MgCl
Mg, THF
Cl MgCl
Mg, Et2O
O
O
Cl
O
O
MgCl
Mg, THF
I MgI
Mg, Et2O
Cl MgCl
Mg, Et2O
Br
Mg
Br
Mg
magnesium inserts 
into this bond
magnesium(0)
magnesium(II)
oxidative insertion
R X
Mg
R Mg X
Síntese de reagente de Grinard… 
Inserção oxidativa 
Reagente de Grinard 
173 
 
Prof. Dr. José Eduardo Damas Martins 
Síntese de reagente de Grinard… 
A reação só funciona em éter seco (sem traços 
água) 
The reaction takes place not in solution but on the surface of the metal, and how easy it is to make
a Grignard reagent can depend on the state of the surface—how finely divided the metal is, for exam-
ple. Magnesium is usually covered by a thin coating of magnesium oxide, and Grignard formation
generally requires ‘initiation’ to allow the metal to come into contact with the alkyl halide. Initiation
can be accomplished by adding a small amount of iodine or 1,2-diiodoethane, or by using ultra-
sound to dislodge the oxide layer. The ether solvent is essential for Grignard formation because (1)
ethers (unlike, say, alcohols or dichloromethane) will not react with Grignards and, more impor-
tantly, (2) only in ethers are Grignard reagents soluble. In Chapter 5 you saw how triethylamine
forms a complex with the Lewis acid BF3, and much the same happens when an ether meets a metal
ion such as magnesium or lithium: the metals are Lewis-acidic because they have empty orbitals (2p
in the case of Li and 3p in the case of Mg) that can accept the lone pair of the ether.
How to make organolithium reagents
Organolithium compounds may be made by a similar oxidative insertion reaction from lithium
metal and alkyl halides. Each inserting reaction requires two atoms of lithium and generates one
equivalent of lithium halide salt. As with Grignard formation, there is really very little limit on the
types of organolithium that can be made this way.
Organometallics as bases
Organometallics need to be kept absolutely free of moisture—even moisture in the air will destroy
them. The reason is that they react very rapidly and highly exothermically with water to produce
212 9 . Using organometallic reagents to make C–C bonds
R
Mg
X
OO
complex between 
Lewis-acidic metal atom 
and lone pairs of THF
R X
R Li LiX
Li, THF
alkylithium plus lithium halide
R can be alkyl 
or aryl
X can be I, Br 
or Cl
MeCl MeLi + LiCl
Li, Et2O Cl Li
+ LiCl
Li, hexane, 
50 °C
Cl Li
+ LiCl
Li, pentane
Br Li
OMe OMe
+ LiBr
Li, THF
Cl Li + LiCl
Li, THF
Br Li + LiBr
Li, Et2O
Most chemists (unless they were working on a very large
scale) would not usually make the simpler organolithiums
or Grignard reagents by these methods, but would buy
them in bottles from chemical companies (who, of course,
do use these methods). The table lists some of the most
important commercially available organolithiums and
Grignard reagents.
Some Grignard and organolithium reagents are commercially available
Commercially available organometallics
methyllithium (MeLi) methylmagnesium chloride, bromide, and iodide
(MeMgX)
n-butyllithium (n-BuLi or just BuLi) ethylmagnesium bromide (EtMgBr)
sec-butyllithium (sec-BuLi or s-BuLi) butylmagnesium chloride (BuMgCl)
tert-butyllithium (tert-BuLi or t-BuLi) allylmagnesium chloride and bromide 
phenyllithium (PhLi) phenylmagnesium chloride and bromide (PhMgCl or
PhMgBr)
Li
Li
Li
MgX
A complexação 
facilita a 
solubilização do 
reagente 
02/09/14 
21 
174 
 
Prof. Dr. José Eduardo Damas Martins 
electronegative an atom is, the lower in energy its atomic orbitals are (p. 000). The filled C–Li σ
orbital that arises is closer in energy to the carbon’s sp3 orbital than to the lithium’s 2s orbital, so we
can say that the carbon’s sp3 orbital makes a greater contribution to the C–Li σ bond and that the
C–Li bond has a larger coefficient on carbon. Reactions involving the filled σ orbital will therefore
take place at C rather than Li. The same arguments hold for the C–Mg bond of Grignard reagents.
We can also say that, because the carbon’s sp3 orbital makes a greater contribution to the C–Li σ
bond, the σ bond resembles a filled C sp3 orbital—in other words it resembles a lone pair on carbon. This
is a useful idea because it allows us to
think about the way in which methyl-
lithium reacts—as though it were an
ionic compound Me–Li+—and you
may sometimes see MeLi or MeMgCl
represented in mechanisms as Me–.
Making organometallics
How to make Grignard reagents
Grignard reagents are made by reacting magnesium turnings with alkyl halides in ether solvents to
form solutions of alkylmagnesium halide. Iodides, bromides, and chlorides can be used, as can both
aryl and alkyl halides, though they cannot contain any functional groups that would react with the
Grignard reagent once it is formed. Here are some examples.
The reaction scheme is easy enough to draw, but what is the
mechanism? Overall it involves an insertion of magnesium into the
new carbon–halogen bond. There is also a change in oxidation state
of the magnesium, from Mg(0) to Mg(II). The reaction is therefore
known as an oxidative insertion or oxidative addition, and is a
general process for many metals such as Mg, Li (which we meet
shortly), Cu, and Zn.
The mechanism of the reaction is not completely understood
but a possible (but probably not very accurate) way of writing the
mechanism is shown here: the one thing that is certain is that the
first interaction is between the metal and the halogen atom.
Making organometallics 211
!
You have already met cyanide (p.
000), a carbon nucleophile that
really does have a lone pair on
carbon. Cyanide’s lone pair is
stabilized by being in a lower-
energy sp orbital (rather than sp3)
and by having the electronegative
nitrogen atom triply bonded to the
carbon.
!
Carbon atoms that carry a
negative charge, for example
Me–, are known as carbanions.
R Li R Li
R MgX R MgX
organometallic carbanion metal cation
+
+
reacts as though it were
reacts as though it were
Even though these organometallic compounds are extremely
reactive with water and oxygen, and have to be handled
under an atmosphere of nitrogen or argon, a number have
been studied by X-ray crystallography in the solid state and
by NMR in solution. It turns out that they generally form
complex aggregates with two, four, six, or more molecules
bonded together, often with solvent molecules. In this book
we shall not be concerned with these details, and it will
suffice always to represent organometallic compounds as
simple monomeric structures.
The true structure of organolithiums and Grignard reagents is rather more
complicated!
R X
R Mg X
Mg, Et2O
alkylmagnesium halide
(Grignard reagent)
R can be alkyl 
or aryl
X can be I, Br, 
or Cl
!
Diethyl ether (Et2O) and THF are
the most commonly used
solvents, but you may also meet
others such as dimethoxyethane
(DME) and dioxane.
O
O
O
O
MeO
OMe
common ether solvents
diethyl ether THF
(tetrahydrofuran)
dioxane
DME
(dimethoxyethane)
Br MgBr
Mg, THF
MeI MeMgI
Mg, Et2O
Cl MgCl
Mg, THF
Cl MgCl
Mg, Et2O
O
O
Cl
O
O
MgCl
Mg, THF
I MgI
Mg, Et2O
Cl MgCl
Mg, Et2O
Br
Mg
Br
Mg
magnesium inserts 
into this bond
magnesium(0)
magnesium(II)
oxidative insertion
R X
Mg
R Mg X
Síntese de reagente de Grinard… 
175 
 
Prof. Dr. José Eduardo Damas Martins 
electronegative an atom is, the lower in energy its atomic orbitals are (p. 000). The filled C–Li σ
orbital that arises is closer in energy to the carbon’s sp3 orbital than to the lithium’s 2s orbital, so we
can say that the carbon’s sp3 orbital makes a greater contribution to the C–Li σ bond and that the
C–Li bond has a larger coefficient on carbon. Reactions involving the filled σ orbital will therefore
take place at C rather than Li. The same arguments hold for the C–Mg bond of Grignard reagents.
We can also say that, because the carbon’s sp3 orbital makes a greater contribution to the C–Li σ
bond, the σ bond resembles a filled C sp3 orbital—in other words it resembles a lone pair on carbon. This
is a useful idea because it allows us to
think about the way in which methyl-
lithium reacts—as though it were an
ionic compound Me–Li+—and you
may sometimes see MeLi or MeMgCl
represented in mechanisms as Me–.
Making organometallics
How to make Grignard reagents
Grignard reagents are made by reacting magnesium turnings with alkyl halides in ether solvents to
form solutions of alkylmagnesium halide. Iodides, bromides, and chlorides can be used, as can both
aryl and alkyl halides, though they cannot contain any functional groups that would react with the
Grignard reagent once it is formed. Here are some examples.
The reaction scheme is easy enough to draw, but what is the
mechanism? Overall it involves an insertion of magnesium into the
new carbon–halogen bond. There is also a change in oxidation state
of the magnesium, from Mg(0) to Mg(II). The reaction is therefore
known as an oxidative insertion or oxidative addition, and is a
general process for many metals such as Mg, Li (which we meet
shortly), Cu, and Zn.
The mechanism of the reaction is not completely understood
but a possible (but probably not very accurate) way of writing the
mechanism is shown here: the one thing that is certain is that the
first interaction is between the metal and the halogen atom.
Making organometallics 211
!
You have already met cyanide (p.
000), a carbon nucleophile that
really does have a lone pair on
carbon. Cyanide’s lone pair is
stabilized by being in a lower-
energy sp orbital (rather than sp3)
and by having the electronegative
nitrogen atom triply bonded to the
carbon.
!
Carbon atoms that carry a
negative charge, for example
Me–, are known as carbanions.
R Li R Li
R MgX R MgX
organometallic carbanion metal cation
+
+
reacts as though it were
reacts as though it were
Even though these organometallic compounds are extremely
reactive with water and oxygen, and have to be handled
under an atmosphere of nitrogen or argon, a number have
been studied by X-ray crystallography in the solid state and
by NMR in solution. It turns out that they generally form
complex aggregates with two, four, six, or more molecules
bonded together, often with solvent molecules. In this book
we shall not be concerned with these details, and it will
suffice always to represent organometallic compounds as
simple monomeric structures.
The true structure of organolithiums and Grignard reagents is rather more
complicated!
R X
R Mg X
Mg, Et2O
alkylmagnesium halide
(Grignard reagent)
R can be alkyl 
or aryl
X can be I, Br, 
or Cl
!
Diethyl ether (Et2O) and THF are
the most commonly used
solvents, but you may also meet
others such as dimethoxyethane
(DME) and dioxane.
O
O
O
O
MeO
OMe
common ether solvents
diethyl ether THF
(tetrahydrofuran)
dioxane
DME
(dimethoxyethane)
Br MgBr
Mg, THF
MeI MeMgI
Mg, Et2O
Cl MgCl
Mg, THF
Cl MgCl
Mg, Et2O
O
O
Cl
O
O
MgCl
Mg, THF
I MgI
Mg, Et2O
Cl MgCl
Mg, Et2O
Br
Mg
Br
Mg
magnesium inserts 
into this bond
magnesium(0)
magnesium(II)
oxidative insertion
R X
Mg
R Mg X
Síntese de reagente de Grinard… 
electronegative an atom is, the lower in energy its atomic orbitals are (p. 000). The filled C–Li σ
orbital that arises is closer in energy to the carbon’s sp3 orbital than to the lithium’s 2s orbital, so we
can say that the carbon’s sp3 orbital makes a greater contribution to the C–Li σ bond and that the
C–Li bond has a larger coefficient on carbon. Reactions involving the filled σ orbital will therefore
take place at C rather than Li. The same arguments hold for the C–Mg bond of Grignard reagents.
We can also say that, because the carbon’s sp3 orbital makes a greater contribution to the C–Li σ
bond, the σ bond resembles a filled C sp3 orbital—in other words it resembles a lone pair on carbon. This
is a useful idea because it allows us to
think about the way in which methyl-
lithium reacts—as though it were an
ionic compound Me–Li+—and you
may sometimes see MeLi or MeMgCl
represented in mechanisms as Me–.
Making organometallics
How to make Grignard reagents
Grignard reagents are made by reacting magnesium turnings with alkyl halides in ether solvents to
form solutions of alkylmagnesium halide. Iodides, bromides, and chlorides can be used, as can both
aryl and alkyl halides, though they cannot contain any functional groups that would react with the
Grignard reagent once it is formed. Here are some examples.
The reaction scheme is easy enough to draw, but what is the
mechanism? Overall it involves an insertion of magnesium into the
new carbon–halogen bond. There is also a change in oxidation state
of the magnesium, from Mg(0) to Mg(II). The reaction is therefore
known as an oxidative insertion or oxidative addition, and is a
general process for many metals such as Mg, Li (which we meet
shortly), Cu, and Zn.
The mechanism of the reaction is not completely understood
but a possible (but probably not very accurate) way of writing the
mechanism is shown here: the one thing that is certain is that the
first interaction is between the metal and the halogen atom.
Making organometallics 211
!
You have already met cyanide (p.
000), a carbon nucleophile that
really does have a lone pair on
carbon. Cyanide’s lone pair is
stabilized by being in a lower-
energy sp orbital (rather than sp3)
and by having the electronegative
nitrogen atom triply bonded to the
carbon.
!
Carbon atoms that carry a
negative charge, for example
Me–, are known as carbanions.
R Li R Li
R MgX R MgX
organometallic carbanion metal cation
+
+
reacts as though it were
reacts as though it were
Even though these organometallic compounds are extremely
reactive with water and oxygen, and have to be handled
under an atmosphere of nitrogen or argon, a number have
been studied by X-ray crystallography in the solid state and
by NMR in solution. It turns out that they generally form
complex aggregates with two, four, six, or more molecules
bonded together, often with solvent molecules. In this book
we shall not be concerned with these details, and it will
suffice always to represent organometallic compounds as
simple monomeric structures.
The true structure of organolithiums and Grignard reagents is rather more
complicated!
R X
R Mg X
Mg, Et2O
alkylmagnesium halide
(Grignard reagent)
R can be alkyl 
or aryl
X can be I, Br, 
or Cl
!
Diethyl ether (Et2O) and THF are
the most commonly used
solvents, but you may also meet
others such as dimethoxyethane
(DME) and dioxane.
O
O
O
O
MeO
OMe
common ether
solvents
diethyl ether THF
(tetrahydrofuran)
dioxane
DME
(dimethoxyethane)
Br MgBr
Mg, THF
MeI MeMgI
Mg, Et2O
Cl MgCl
Mg, THF
Cl MgCl
Mg, Et2O
O
O
Cl
O
O
MgCl
Mg, THF
I MgI
Mg, Et2O
Cl MgCl
Mg, Et2O
Br
Mg
Br
Mg
magnesium inserts 
into this bond
magnesium(0)
magnesium(II)
oxidative insertion
R X
Mg
R Mg X
02/09/14 
22 
176 
 
Prof. Dr. José Eduardo Damas Martins 
Organometálicos à partir de 
alcinos 
Alquinos podem ser deprotonados por bases 
fortes. 
177 
 
Prof. Dr. José Eduardo Damas Martins 
alkanes. Anything that can protonate them will do the same thing. If we represent these protonation
reactions slightly differently, putting the products on the left and the starting materials (represented,
just for effect, as ‘carbanions’) on the right, you can see that that they are acid–base equilibria from
the last chapter. The organometallic acts as a base, and is protonated to form its conjugate acid—
methane or benzene in these cases.
The equilibria lie vastly to the left: the pKa values indicate that methane and benzene are extreme-
ly weak acids and that methyllithium and phenylmagnesium bromide must therefore be extremely
strong bases. Some of the most important uses of organolithiums—butyllithium, in particular—are
as bases and, because they are so strong, they will deprotonate almost anything. That makes them
very useful as reagents for making other organolithiums.
Making organometallics by deprotonating alkynes
In Chapter 8 (p. 000) we talked about how hybridization affects acidity. Alkynes, with their C–H
bonds formed from sp orbitals, are the most acidic of hydrocarbons, with pKas of about 25. They
can be deprotonated by more basic organometallics such as butyllithium or ethylmagnesium
bromide. Alkynes are sufficiently acidic to be deprotonated even by nitrogen bases, and another
common way of deprotonating alkynes is to use NaNH2 (sodium amide), obtained by reacting
sodium with liquid ammonia. An example of each is shown here: we have chosen to repre-
sent the alkynyllithium and alkynylmagnesium halide as organometallics and the alkynyl sodium
as an ionic salt. Propyne and acetylene are gases, and can be bubbled through a solution of the
base.
The metal derivatives of alkynes can be added to carbonyl electrophiles as in the following exam-
ples. The first (we have reminded you of the mechanism for this) is the initial step of an important
synthesis of the antibiotic, erythronolide A, and the second is the penultimate step of a synthesis of
the widespread natural product, farnesol.
Making organometallics 213
MeLi
H
Me H
+ Li
Me H3OMe H H2O
methane
+ +
pKa = 43
PhBrMg
H
Ph H Ph H3OPh H H2O
+ Mg2 + Br
benzene
+ +
pKa = 48
n-Bu Li n-Bu HLiH
 THF
–78 °C
+ +
1-hexyne n-butyllithium 1-hexynyllithium butane
pKa ca. 50pKa ca. 26
Et MgBr Et HMgBrMeHMe
 THF
20 °C
+ +
propyne ethylmagnesium 
bromide
propynylmagnesium bromide ethane
Na NH2 NH3HH H Na 
–78 ˚C
+ +
ethyne (acetylene) "sodium acetylide" ammonia
pKa ca. 35
Organometálicos à partir de alcinos… 
Ácido mais fraco, 
base conjugada 
mais forte 
02/09/14 
23 
178 
 
Prof. Dr. José Eduardo Damas Martins 
Organometálicos à partir de alcinos… 
alkanes. Anything that can protonate them will do the same thing. If we represent these protonation
reactions slightly differently, putting the products on the left and the starting materials (represented,
just for effect, as ‘carbanions’) on the right, you can see that that they are acid–base equilibria from
the last chapter. The organometallic acts as a base, and is protonated to form its conjugate acid—
methane or benzene in these cases.
The equilibria lie vastly to the left: the pKa values indicate that methane and benzene are extreme-
ly weak acids and that methyllithium and phenylmagnesium bromide must therefore be extremely
strong bases. Some of the most important uses of organolithiums—butyllithium, in particular—are
as bases and, because they are so strong, they will deprotonate almost anything. That makes them
very useful as reagents for making other organolithiums.
Making organometallics by deprotonating alkynes
In Chapter 8 (p. 000) we talked about how hybridization affects acidity. Alkynes, with their C–H
bonds formed from sp orbitals, are the most acidic of hydrocarbons, with pKas of about 25. They
can be deprotonated by more basic organometallics such as butyllithium or ethylmagnesium
bromide. Alkynes are sufficiently acidic to be deprotonated even by nitrogen bases, and another
common way of deprotonating alkynes is to use NaNH2 (sodium amide), obtained by reacting
sodium with liquid ammonia. An example of each is shown here: we have chosen to repre-
sent the alkynyllithium and alkynylmagnesium halide as organometallics and the alkynyl sodium
as an ionic salt. Propyne and acetylene are gases, and can be bubbled through a solution of the
base.
The metal derivatives of alkynes can be added to carbonyl electrophiles as in the following exam-
ples. The first (we have reminded you of the mechanism for this) is the initial step of an important
synthesis of the antibiotic, erythronolide A, and the second is the penultimate step of a synthesis of
the widespread natural product, farnesol.
Making organometallics 213
MeLi
H
Me H
+ Li
Me H3OMe H H2O
methane
+ +
pKa = 43
PhBrMg
H
Ph H Ph H3OPh H H2O
+ Mg2 + Br
benzene
+ +
pKa = 48
n-Bu Li n-Bu HLiH
 THF
–78 °C
+ +
1-hexyne n-butyllithium 1-hexynyllithium butane
pKa ca. 50pKa ca. 26
Et MgBr Et HMgBrMeHMe
 THF
20 °C
+ +
propyne ethylmagnesium 
bromide
propynylmagnesium bromide ethane
Na NH2 NH3HH H Na 
–78 ˚C
+ +
ethyne (acetylene) "sodium acetylide" ammonia
pKa ca. 35
Ácido mais fraco, 
base conjugada 
mais forte 
179 
 
Prof. Dr. José Eduardo Damas Martins 
alkanes. Anything that can protonate them will do the same thing. If we represent these protonation
reactions slightly differently, putting the products on the left and the starting materials (represented,
just for effect, as ‘carbanions’) on the right, you can see that that they are acid–base equilibria from
the last chapter. The organometallic acts as a base, and is protonated to form its conjugate acid—
methane or benzene in these cases.
The equilibria lie vastly to the left: the pKa values indicate that methane and benzene are extreme-
ly weak acids and that methyllithium and phenylmagnesium bromide must therefore be extremely
strong bases. Some of the most important uses of organolithiums—butyllithium, in particular—are
as bases and, because they are so strong, they will deprotonate almost anything. That makes them
very useful as reagents for making other organolithiums.
Making organometallics by deprotonating alkynes
In Chapter 8 (p. 000) we talked about how hybridization affects acidity. Alkynes, with their C–H
bonds formed from sp orbitals, are the most acidic of hydrocarbons, with pKas of about 25. They
can be deprotonated by more basic organometallics such as butyllithium or ethylmagnesium
bromide. Alkynes are sufficiently acidic to be deprotonated even by nitrogen bases, and another
common way of deprotonating alkynes is to use NaNH2 (sodium amide), obtained by reacting
sodium with liquid ammonia. An example of each is shown here: we have chosen to repre-
sent the alkynyllithium and alkynylmagnesium halide as organometallics and the alkynyl sodium
as an ionic salt. Propyne and acetylene are gases, and can be bubbled through a solution of the
base.
The metal derivatives of alkynes can be added to carbonyl electrophiles as in the following exam-
ples. The first (we have reminded you of the mechanism for this) is the initial step of an important
synthesis