15
Organic
Chemistry
William H. Brown &
Christopher S. Foote
15-1
15
Organometallic
Compounds
Chapter 15
15-2
15 Organometallic Compounds
 Organometallic
compound: a compound that
contains a carbon-metal bond
 We focus on organometallic compounds of Mg,
Li, Cu, Zn, Pd, and Ru
• 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
15-3
15 Organometallic Compounds
 Oxidative
addition: a reagent adds to a metal or
metal compound, causing its coordination to
increase by two
 Reductive elimination: a reagent is eliminated
from a metal compound, causing its coordination
to decrease by two
 Ligand: a Lewis base bonded to a metal in a
coordination compound
MLn
+ X2
oxidative
addition
X
reductive X
elimination
MLn
15-4
15 Grignard Reagent
 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
Mg Br
Butylmagnesium bromide
(an alkyl Grignard reagent)
ether
Mg Br
Phenylmagnesium
bromide
(an aryl Grignard reagent)
15-5
15 RMgX and RLi
 Grignard
reagents dissolve as coordination
compounds solvated by ether
• ethylmagnesium bromide, EtMgBr
15-6
15 RMgX and RLi
 Organolithium
reagents
• prepared by reaction of an alkyl, aryl, or alkenyl halide
with lithium metal
Cl + 2 Li
1-Chlorobutane
pentane
Li
Butyllithium
+
LiCl
15-7
15 RMgX and RLi
 The
carbon-metal bonds in RMgX and RLi are
polar covalent
C-M
Bond
Difference in
Percent Ionic
Electronegativity character*
C-Li
C-Mg
C-A l
C-Zn
C-Sn
C-Cu
C-H g
2.5 - 1.0 = 1.5
2.5 - 1.2 = 1.3
2.5 - 1.5 = 1.0
2.5 - 1.6 = 0.9
2.5 - 1.8 = 0.7
2.5 - 1.9 = 0.6
2.5 - 1.9 = 0.6
*Percent ionic character =
60
52
40
36
28
24
24
EC - EM
EC
x 100
15-8
15 RMgX and RLi
 RMgX
and RLi are valuable in synthesis as
nucleophiles
• the carbon bearing the halogen is transformed from an
electrophile to a nucleophile
carbon is an
electrophile
H
+ C Br
CH3 CH2 CH2
H
carbon is a
nucleophile
H
H
C
CH3 CH2 CH2
-
Mg 2 + Br
-
• their most valuable use is addition to the electrophilic
carbon of a C=O group to form a new carbon-carbon
bond
15-9
15 RMgX and RLi
 Reaction
with protic acids
• RMgX and RLi are strong bases
+
+ CH3 CH2 - Mg Br + H- OH
pK a 15.7
Stronger
Stronger
base
acid
CH3 CH2 - H + Mg 2 + + OH - + Br pK a 51
Weaker
acid
pK eq = -35
Weaker
base
15-10
15 RMgX and RLi
 Reaction
with protic acids
• RMgX and RLi react readily with these proton donors
R2 NH
pK a 38-40
RC CH
pK a 25
ROH
pK a 16-18
1° and 2°
Amines
Terminal
alkynes
Alcohols
HOH
pK a 15.7
A rOH
pK a 9-10
RSH
pK a 8-9
RCOOH
pK a 4-5
Water
Phenols
Thiols
Carboxylic
acids
15-11
15 RMgX and RLi
 Reaction
with oxiranes (epoxides)
• reaction of RMgX or RLi with an oxirane followed by
protonation increases chain length by two carbons
Mg Br +
Butylmagnesium
bromide
O
Ethylene
oxide
O - MgBr+
A magnesium
alkoxide
HCl
H2 O
OH
1-Hexanol
15-12
15 RMgX and RLi
 Reaction
with oxiranes (epoxides)
• the major product corresponds to SN2 attack of RMgX
or RLi on less hindered carbon of the epoxide
Mg Br
+
Phenylmagnesium
bromide
O
Methyloxirane
(Propylene
oxide)
HCl
O - MgBr+
A magnesium
alkoxide
H2 O
OH
1-Phenyl-2-propanol
15-13
15 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
or THF
Copper(I)
iodide
2 CH3 CH2 CH2 CH2 Li +
Butyllithium
CuI
( CH3 CH2 CH2 CH2 ) 2 Cu - Li
+
+ LiI
Lithium dibutylcopper
(a Gilman reagent)
15-14
15 Gilman Reagents
 Coupling
within organohalogen compounds
• form new carbon-carbon bonds by coupling with alkyl
chlorides, bromides, and iodides
R' Br + R2 CuLiBr
diethyl ether
or THF
[ CH3 ( CH 2 ) 8 CH2 ] 2 CuLi
Lithium didecylcopper
+
Br
R' -R + RCu +
LiBr
diethyl ether
or THF
2-Bromopropene
CH2 ( CH2 ) 8 CH 3 + CH3 ( CH2 ) 8 CH 2 Cu
2-Methyl-1-dodecene
15-15
15 Gilman Reagents
• coupling with a vinylic halide is stereospecific; the
configuration of an alkene is retained
CH 3 ( CH 2 ) 6
H
C C
+ ( CH 3 CH 2 CH2 CH2 ) 2 CuLi
diethyl ether
or THF
H
I
E-1-Iodo-1-nonene
CH 3 ( CH2 ) 6
H
C C
H
CH2 CH2 CH2 CH 3
E-5-Tridecene
15-16
15 Gilman Reagents
A
variation on the preparation of a Gilman
reagent is to use a Grignard reagent with a
catalytic amount of copper(I) salt
CH 3 ( CH2 )
7
( CH2 ) 7 CH 2 Br
C C
H
H
(Z)-1-Bromo-9octadecene
+ CH 3 ( CH 2 ) 4 MgBr
Cu+
THF
CH 3 ( CH2 ) 7 ( CH2 ) 1 2 CH3
C C
H
H
(Z)-9-Tricosene
(Muscalure)
15-17
15 Gilman Reagents
 Reaction
with epoxides
• regioselective ring opening
O
OH
1 . ( CH2 = CH) 2 CuLi
2 . H2 O, HCl
Styrene oxide
1-Phenyl-3-buten-1-ol
15-18
15 Heck Reaction
A
palladium catalyzed reaction in which the
carbon group of a haloalkene or haloarene is
substituted for a vinylic H of an alkene
R-X
+
H
Haloalkene Alkene
or Haloarene
+
B
Pd catalyst
Heck reaction
Base
R
+
BH+ X-
Substituted Conjugate acid
alkene
of the base
15-19
15 Heck Reaction
• substitution is highly regioselective; at the less
substituted carbon
• substitution is highly stereoselective; where E,Z
isomerism is possible in the product, the E
configuration is often formed almost exclusively
Br
Bromobenzene
+
O
CH2 = CHCOCH 3
Methyl 2-propenoate
(Methyl acrylate)
Pd catalyst
Heck reaction
O
COCH 3
Methyl (E)-3-phenyl-2-propenoate
(Methyl cinnamate)
15-20
15 Heck Reaction
• reaction is stereospecific with regard to the
haloalkene; the configuration of the double bond is
retained
Z
I
(Z)-3-Iodo-3-hexene
Pd catalyst
Heck reaction
+
Phenylethene
(Styrene)
Z
(1E,3Z)-1-Phenyl-3-ethyl1,3-hexadiene
15-21
15 Heck Reaction
 The
catalyst
• most commonly Pd(II) acetate
• reduced in situ to Pd(0)
• reaction of Pd(0) with good ligands gives PdL2
 The
organic halogen compound
• aryl, heterocyclic, and vinylic iodides, chlorides, and
bromides
• alkyl halides with an easily eliminated b hydrogen are
rarely used because they undergo b-elimination to give
alkenes
• OH group, C=O groups of aldehydes & ketones, and
esters unreactive under Heck conditions
15-22
15 Heck Reaction
 The
alkene
• the less the crowding on the alkene, the more reactive
it is
 The
base
• triethylamine, sodium and potassium acetate, and
sodium hydrogen carbonate are most common
 The
solvent
• polar aprotic solvents such as DMF, acetonitrile, DMSO
• aqueous methanol may also be used
 The
ligand
• triphenylphosphine is one of the most common
15-23
15
BH+ X-
oxidative
addition
L 2 Pd
1
R- X
L 2 Pd
B:
5
HX
reductive
elimination
The catalytic
cycle of the
Heck reaction
X
4
R2
syn
elimination
R3
R
L 2 Pd
R4
R3
R4
H
2
R3
R2
X
L 2 Pd
R4
R3
R
H
R2
3
X
R4
R
syn
addition
L 2 Pd
H
X
rotation about the
C-C bond by 60°
H
R
R2
15-24
15 Heck Reaction
• the usual pattern of acyclic compounds is replacement
of a hydrogen of the double bond with an R group
• if the organopalladium group attacks a double bond so
that the R group has no syn H for syn elimination, then
the double bond may shift
I
+
Pd(OAc)2
(C2H5)3N
H
PdL 2 OAc
H H
Formed as a
racemic mixture
15-25
15 Carbenes and Carbenoids
 Carbene,
R2C: a neutral molecule in which a
carbon atom is surrounded by only six valence
electrons
 Methylene, the simplest carbene
• prepared by photolysis or thermolysis of
diazomethane
:
+
H2 C N N:
h
H2 C: + : N N:
Methylene
(the simplest
carbene)
• methylene prepared in this manner is so nonselective
that it is of little synthetic use
15-26
15 Carbenes and Carbenoids
 Dichlorocarbene
• prepared by treating chloroform with potassium tertbutoxide
+ ( CH3 ) 3 CO - K+
Trichloromethane
Potassium
(Cloroform)
tert-butoxide
CHCl 3
Cl 2 C: + ( CH3 ) 3 COH
Dichlorocarbene
+ K+ Cl-
tert-Butyl
alcohol
15-27
15 Carbenes and Carbenoids
 Dichlorocarbene
• reacts with alkenes to give dichlorocyclopropanes
H
Cl 2 C:
+
Dichlorocarbene
+ HCCl 3
CCl2
H
A dichlorocyclopropane
( CH3 ) 3 CO - K+
Cl
H
cis-3-Hexene
H
Cl
cis-1,1-Dichloro2,3-diethylcyclopropane
15-28
15 Carbenes and Carbenoids
 Simmons-Smith
reaction
• a way to add methylene to an alkene to form a
cyclopropane
• generation of the Simmons-Smith reagent
CH2 I 2
Diiodomethane
+
Zn( Cu)
Zinc-copper
couple
ICH2 ZnI
diethyl ether
Iodomethylzinc iodide
(Simmons-Smith reagent)
• this organozinc compound reacts with a wide variety
of alkenes to give cyclopropanes
15-29
15 Carbenes and Carbenoids
 Simmons-Smith
reagent
+ CH2 I 2
Methylenecyclopentane
Zn( Cu)
+ ZnI 2
diethyl ether
Spiro[4.2]heptane
O
O
+ CH2 I 2
2-Cyclohexenone
Zn( Cu)
diethyl ether
H
CH2 + ZnI 2
H
Bicyclo[4.1.0]heptan-2-one
15-30
15 Carbenes and Carbenoids
 Simmons-Smith
reaction
• the organozinc compound reacts with an alkene by a
concerted mechanism
I
CH2
I Zn
ZnI 2 + H2C
15-31
15 Stable Nucleophilic Carbenes
 Stable
nucleophilic carbenes
• certain carbenes with strongly electron-donating
groups are particularly stable
• their stability is enhanced by bulky groups that hinder
self-reactions; one such group is the 2,4,6trimethylphenyl group
• rather than behaving as electron-deficient reagents
like most carbenes, these compounds are
nucleophiles because of the strong electron donation
by the nitrogens
15-32
15 Stable Nucleophilic Carbenes
• this carbene is stabilized by the electron-donating
nitrogens and the bulky 2,4,6-trimethylphenyl groups
N:
N:
+
N:
:
N
:
N
:
N+
15-33
15 Ring-Closing Alkene Metathesis
 Alkene
metathesis reaction: two alkenes
interchange carbons on their double bonds
A
A
B
B
catalyst
+
A
A
B
A
A
B
A
A
+
B
B
B
B
• if the reaction involves 2,2-disubstituted alkenes,
ethylene is lost to give a single alkene product
A
A
B
B
+
H
H
H
H
A
A
catalyst
+
B
CH2=CH2
B
15-34
15 Ring-Closing Alkene Metathesis
• a useful variant of this reaction uses a starting material
in which both alkenes are in the same molecule, and
the product is a cycloalkene
EtOOC
COOEt
catalyst
EtOOC
COOEt
+ CH2 = CH2
15-35
15 Ring-Closing Alkene Metathesis
• a particularly useful alkene methathesis catalyst
consists of ruthenium, Ru, complexed with a
nucleophilic carbene and another carbenoid ligand. In
this example, the other carbenoid ligand is a
benzylidene group.
R
N
nucleophilic
carbenes
N
R
Cl
Cl
R
N
Ru
C6H5
N
R
15-36
15 Ring-Closing Alkene Metathesis
 Like
the Heck reaction, alkene metathesis
involves a catalytic cycle
• addition of a metalocarbenoid to the alkene gives a
four-membered ring
• elimination of an alkene in the opposite direction gives
a new alkene
[M]
R1
R2
R2
[M]
+
R1
R1
R1
R1
R1
+
[M]
R2
A metallacycle
15-37
15 Prob 15.9
Complete these reactions involving Gilman reagents.
(a)
+
Br
CuLi
ether
2
Br
CuLi
+
(b)
I
(c)
+
H
(d)
ether
2
C
2
ether
H
H3 C
CuLi
C C
+
Cl
CuLi
H
CH2
ether
2
15-38
15 Prob 15.13
Show reagents to synthesize this target molecule from
cyclohexane.
OH
O
Br
15-39
15 Prob 15.14
Complete these equations.
(a) CH3 CH2 CH2 C CH + CH3 CH2 Mg Br
diethyl ether
O
Zn( Cu)
diethyl ether
(b)
+ CH2 I 2
(c)
+ CHBr3 + ( CH3 ) 3 CO - K+
(d)
+ CH2 I 2
O
(e)
Zn( Cu)
diethyl ether
CH= CH2 + CH2 I 2
Zn( Cu)
diethyl ether
15-40
15 Prob 15.15
Account for the stereospecificity of this reaction.
H
OH
Zn( Cu)
+
H
CH2 I 2
H
OH
CH2
diethyl ether
H
15-41
15 Prob 15.18
Account for the stereospecificity of this Heck reaction;
that is, that the E alkene is formed exclusively.
O
OCH3
+ C6 H5 Br
Pd( OA c ) 2 , 2 Ph 3 P
( CH3 CH2 ) 3 N
O
C6 H5
OCH3
15-42
15 Prob 15.19
Account for the formation of these isomeric alkenes in
this Heck reaction.
+ C6 H5 Br
(E)-3-Hexene
Pd( OA c ) 2 , 2 Ph 3 P
( CH3 CH2 ) 3 N
C6 H5
C6 H5
+
(Z)-3-Phenyl3-hexene
(E)-4-Phenyl2-hexene
15-43
15 Prob 15.20
Complete these Heck reactions.
(a) 2 C6 H5 CH= CH2 + I
I
( CH3 CH2 ) 3 N
O
(b) CH2 = CHCOCH 3 +
Pd( OA c ) 2 , 2 Ph 3 P
Pd( OA c ) 2 , 2 Ph 3 P
I
( CH3 CH2 ) 3 N
15-44
15 Prob 15.21
Account for the formation of 3-phenylcyclohexene and
the fact that no 1-phenylcyclohexene is formed.
+ C6 H5 I
Pd( OA c ) 2 , 2 Ph 3 P
( CH 3 CH2 ) 3 N
C6 H5
C6 H5
+
3-Phenylcyclohexene
(the only product)
1-Phenylcyclohexene
(not formed)
15-45
15 Prob 15.22
Account for the formation of this product and the cis
stereochemistry of its ring junction.
COOMe
COOMe
Pd( OA c ) 2 , 2 Ph 3 P
I
( CH3 CH 2 ) 3 N
H
86%
15-46
15 Prob 15.23
Account for the formation of the following product,
including the cis stereochemistry at the ring junction.
R
Pd( OAc ) 2 , ( R) -BINAP
R
K2 CO3
T fO
H
15-47
15 Prob 15.24
Show how Exaltolide can be synthesized from the given
starting material. Give the structure of R.
O
O
OR
O
O
O
Exaltolide
15-48
15 Prob 15.25
Propose a synthesis of spiro[2.2]pentane from organic
compounds of three carbons or less.
15-49
15 Prob 15.26
Predict the product of each alkene metathesis reaction.
OA c
OA c
(a)
(b)
O
5 mole % Ru catalyst
O
CH2 Cl 2 , 40°C, 30 min
O
5 mole % Ru catalyst
CH2 Cl 2 , 40°C, 30 min
15-50
15
Organometallic
Compounds
End Chapter 15
15-51