Chapter 14: Organometallic Compounds - Reagents with
carbon-metal bonds
14.1: Organometallic Nomenclature (please read)
H
H3CH2CH2CH2C-Li
H
C C
H
MgBr
Butyllithium
vinylmagnesium bromide
(H3C)2Cu- Li+
Dimethylcopper lithium
14.2: Carbon-Metal Bonds in Organometallic Compounds
C MgX
Alkyl halides will react with some metals (M0) in ether or THF to
form organometallic reagents
14.3: Preparation of Organolithium Compounds
Organolithium Compounds
R-X
2 Li(0)
R-Li
diethyl ether
C Li
LiX
organolithium reagents are most commonly used as very strong
bases and in reactions with carbonyl compounds
R-X
M(0)
R-M
H2O
R-H + M-OH
2
14.4: Preparation of Organomagnesium Compounds:
Grignard Reagents
R-X
Mg(0)
THF
R-MgX
(Grignard reagent)
R-X can be an alkyl, vinyl, or aryl halide (chloride, bromide,
or iodide)
Solvent: diethyl ether (Et2O) or tetrahydrofuran (THF)
H3CH2C
CH2CH3
diethyl ether (Et2O)
tetrahydrofuran (THF)
Alcoholic solvents and water are incompatible with Grignard
reagents and organolithium reagents.
Reactivity of the alkyl halide: -I > -Br > -Cl >> -F
alkyl halides > vinyl or aryl halides
The solvent or alkyl halides can not contain functional groups
that are electrophilic or acidic. These are incompatible with the
formation of the organomagnesium or organolithium reagent.
Grignard reagents will deprotonate alcohols
HO
Br
Mg0
HO
MgBr
_
O
BrMg
H3O+
HO
Other incompatible groups:
-CO2H, -OH, -SH, NH2, CONHR (amides)
Reactive functional groups:
aldehydes, ketones, esters, amides, halides,
-NO2, -SO2R, nitriles
4
14.5: Organolithium and Organomagnesium Compounds
as Brnsted Bases - Grignard reagents (M = MgX) and
organolithium reagents (M = Li) are very strong bases.
R-M + H2O
R-H + M-OH
(CH3)3C-H
pKa
71
H2N-H
pKa
36
H3CH2C-H
62
H C C H
26
H3C-H
60
Water
16
H
C C
H
H
H
45
H
H
43
Hydrocarbons are very weak acids; their conjugate bases are
5
very strong bases.
Lithium and magnesium acetylides
R C C H
terminal
acetylene
(pKa ~ 26)
R C C H
H3C-H2C-H2C-H2C-Li
THF
butyllithium
H3C-H2C-MgBr
R C C Li
+ H3C-H2C-H2C-H2C-H
pKa > 60
lithium
acetylide
THF
R C C MgBr + H3C-H2C-H
magnesium
acetylide
ethylmagnesium
bromide
14.6: Synthesis of Alcohols Using Grignard Reagents
Grignard reagents react with aldehydes, ketones, and esters
to afford alcohols
O
C
MgX
R:
O
C
ether
O
C
MgX
R
H3O+
OH
C
R
Grignard reagents react with . . .
formaldehyde (H2C=O) to give primary alcohols
Br Mg0, ether
1) H2C=O
2) H3O+
MgBr
OH
aldehydes to give secondary alcohols
Br
MgBr 1)
Mg0, ether
OH
O
H
2) H3O+
ketones to give tertiary alcohols
H
H
H
C C
Mg0, ether
Br
H
H
H
C C
1)
MgBr
2) H3O+
esters to give tertiary alcohols
O
C
2 H3C-Br
2 Mg0, ether
2 H3C-MgBr
OH
1)
2) H3O+
OCH2CH3
OH
C CH
3
CH3
14.10: Preparation of Tertiary Alcohols From Esters and
Grignard Reagents - mechanism:
O
C
OCH2CH3
+ 2 H3C-MgBr
1) THF
2) then H3O+
OH
C CH
3
CH3
Reaction of Grignard reagents with CO2 (Lab, Chapter 19.11)
O
MgBr
Br
Mg(0)
ether
O=C=O
OH
H 3O +
14.7: Synthesis of Alcohols Using Organolithium Reagents
Organolithium reagents react with aldehydes, ketones, and
esters in the same way that Grignard reagents do.
Li
O
C
R-Li
ether
O
C
H3O+
OH
C
R
14.8: Synthesis of Acetylenic Alcohols
+
R C C H
NaNH2
R C C
Na+ +
pKa~ 36
pKa~ 26
R C C H
NH3
H3C(H2C)H2C-Li
R C C
Li+
+ H3C(H2C)CH3
pKa > 60
R C C H
H3CH2C-MgBr
R C C
MgBr+
+ H3CCH3
pKa > 60
Recall from Chapter 9.6
R1 C C
Na
acetylide anion
THF
R2-H2C-Br
R1 C C CH2R2
SN2
NaBr
new C-C
bond formed
1 alkyl halide
Acetylide anions react with ketones and aldehydes to form a
C-C bond; the product is an acetylenic (propargyl) alcohols
R1 C C
MgBr +
R2
O
C
THF
R3
then
H3O+
R1
OH
C C C
R
R2 3
acetylenic alcohol
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14.9: Retrosynthetic Analysis - the process of planning a
synthesis by reasoning backward from the the target molecule
to a starting compound using known and reliable reactions.
it is a problem solving technique for transforming the structure
of a synthetic target molecule (TM) to a sequence of
progressively simpler structures along the pathway which
ultimately leads to simple or commercially available starting
materials for a chemical synthesis.
The transformation of a molecule to a synthetic precursor is
accomplished by:
Disconnection: the reverse operation to a synthetic reaction;
the hypothetical cleavage of a bond back to precursors of the
target molecule.
Functional Group Interconversion (FGI): the process of
converting one functional group into another by substitution,
addition, elimination, reduction, or oxidation
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Each precursor is then the target molecule for further
retrosynthetic analysis. The process is repeated until suitable
starting materials are derived.
Target
molecule
Precursors
1
Precursors
2
Starting
materials
Prepare (Z)-2-hexene from acetylene
Z-2-hexene
2-Phenyl-2-propanol
OH
CH3
CH3
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14.11: Alkane Synthesis Using Organocopper Reagents
2 CH3Li
ether
CuI
H3C
_
Cu Li+
+ LiI
H3C
Gilman's reagent
(dimethylcuprate, dimethylcopper lithium)
R2CuLi
R-
strong nucleophiles
Nucleophilic substitution reactions with alkyl halides and
sulfonates (alkylation)
H3C(H2C)8H2C-I + (H3C)2CuLi
ether
H3C(H2C)8H2C-CH3
+ CH3Cu + LiI
SN2 reaction of cuprates is best with primary and secondary
alkyl halides; tertiary alkyl halides undergo E2 elimination.
13
Vinyl and aryl (but not acetylenic) cuprates
2
Br
4 Li(0), ether
CuI
Li
CuLi
2
Br
Li
4 Li(0), ether
CuI
CuLi
2
CuLi
OTs
THF
2
CuLi
THF
14
Reaction of cuprates with aryl and vinyl halides
H
I
H
Br
(H3C)2CuLi
H
(H3CH2CH2C)2CuLi
double bond geometry
is preserved
CH3
CH2CH2CH3
14.13: Carbenes and Carbenoids
Carbene: highly reactive intermediate, 6-electron species.
The carbon is sp2 hybridized; it possesses a vacant hybridized
p-orbital and an sp2 orbital with a non-bonding pair of electrons
15
Generation and Reaction of Dihalocarbenes:
CHCl3
+
KOH
Cl 2C:
+ H 2O
+ KCl
dichlorocarbene
Carbenes react with alkenes to give cyclopropanes.
Cl Cl
H
CHCl3, KOH
cis-alkene
cis-cyclopropane
Br Br
H
trans-alkene
CHBr3, KOH
trans-cyclopropane
The cyclopropanation reaction takes place in a single step. There
is NO intermediate. As such, the geometry of the alkene is
preserved in the product. Groups that are trans on the alkene will
end up trans on the cyclopropane product. Groups that are cis
on the alkene will end up cis on the cyclopropane product.
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14.12: An Organozinc Reagent for Cyclopropane Synthesis
Simmons-Smith Reaction
CH2I2
Zn(Cu)
ether
I-CH2-Zn-I = H2C:
carbene
CH2I2, Zn(Cu)
ether
The geometry of the alkene is preserved in the cyclopropanation
reaction.
H
CH2I2, Zn(Cu)
ether
cis-alkene
trans-alkene
cis-cyclopropane
CH2I2, Zn(Cu)
ether
trans-cyclopropane
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14.14: Transition-Metal Organometallic Compounds
(please read)
14.15: Homogeneous Catalytic Hydrogenation (please read)
H2, Pd/C - The catalyst is insoluble in the reaction media:
heterogeneous catalysis, interfacial reaction
H2, (Ph3P)3RhCl - The catalyst is soluble in the reaction media:
homogeneous catalysis.
14.16: Olefin Metathesis (please read)
14.17: Ziegler-Natta Catalysis of Alkene Polymerization
(please read)
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