Chapter 14: Organometallic Compounds - Reagents with
carbon-metal bonds
14.1: Organometallic Nomenclature (please read)
H
H
C
H 3 C H 2 C H 2 C H 2 C -L i
H
C
(H 3 C ) 2 C u - L i +
M gB r
v in y lm a g n e siu m b ro m id e
B u ty llith iu m
D im e th ylco p p e r lith iu m
14.2: Carbon-Metal Bonds in Organometallic Compounds
C
X
+ C
X
A lky l h a lid e s:
e le c tro p h ile s
C M gX
- +
C M gX
_
C
C a rb an io ns : n u cle op h ile
re a c t w ith e le c trop h ile
302
Alkyl halides will react with some metals (M0) in ether or THF to
form organometallic reagents
14.3: Preparation of Organolithium Compounds
Organolithium Compounds
2 Li(0)
R-X
R-Li
+
LiX
diethyl ether
- +
C
_
C
Li
very strong bases
very strong nucleophiles
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
303
14.4: Preparation of Organomagnesium Compounds:
Grignard Reagents
R-X
Mg(0)
R-MgX
(Grignard reagent)
THF
R-X can be an alkyl, vinyl, or aryl halide (chloride, bromide,
or iodide)
Solvent: diethyl ether (Et2O) or tetrahydrofuran (THF)
H 3C H 2C
O
C H 2C H 3
O
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
304
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
_
M g0
HO
Br
HO
M gB r
_
O
H
H 3O +
HO
H
B rM g
Other incompatible groups:
-CO2H, -OH, -SH, NH2, CONHR (amides)
Reactive functional groups:
aldehydes, ketones, esters, amides, halides,
-NO2, -SO2R, nitriles
305
14.5: Organolithium and Organomagnesium Compounds
as Brønsted Bases - Grignard reagents (M = MgX) and
organolithium reagents (M = Li) are very strong bases.
R-M + H2O
(CH3)3C-H
H3CH2C-H
H3C-H
H
R-H + M-OH
pKa
71
62
60
H2N-H
H C C H
Water
pKa
36
26
16
H
C
H
H
45
C
H
H
H
H
H
43
H
Hydrocarbons are very weak acids; their conjugate bases are
306
very strong bases.
Lithium and magnesium acetylides
R
C
C
H
+
te rm in a l
a ce tyle n e
(p K a ~ 2 6 )
R
C
C
H
THF
H 3 C -H 2 C -H 2 C -H 2 C -L i
R
b u tyllith iu m
+
H 3 C -H 2 C -M g B r
C
C
+
Li
H 3 C -H 2 C -H 2 C -H 2 C -H
pK a > 60
lith iu m
a ce tylid e
TH F
R
C
C M gBr
+
H 3 C -H 2 C -H
m a g n e s iu m
a c e ty lid e
e th y lm a g n e s iu m
b ro m id e
14.6: Synthesis of Alcohols Using Grignard Reagents
Grignard reagents react with aldehydes, ketones, and esters
to afford alcohols
M gX
O
C
+
O
R:
C
M gX
eth er
H 3O +
O
C
OH
C
R
R
307
Grignard reagents react with . . .
formaldehyde (H2C=O) to give primary alcohols
Br
1) H 2 C =O
2) H 3 O +
M gB r
M g 0 , ethe r
OH
aldehydes to give secondary alcohols
OH
O
Br
M gBr
M g 0 , e the r
1)
H
2) H 3 O +
ketones to give tertiary alcohols
H
H
C
H
M g 0 , e th er
H
C
H
C
Br
H
O
1)
C
M gBr
2 ) H 3O +
esters to give tertiary alcohols
O
C
O C H 2C H 3
2 M g 0 , e th er
2 H 3 C -B r
OH
1)
2 H 3 C -M gB r
2 ) H 3O +
OH
C
CH3
CH3
308
14.10: Preparation of Tertiary Alcohols From Esters and
Grignard Reagents - mechanism:
O
C
O C H 2C H 3
+
1) T H F
2) th en H 3 O +
OH
C
2 H 3 C -M gB r
CH3
CH3
Reaction of Grignard reagents with CO2 (Lab, Chapter 19.11)
_
O
O
O
M gB r
Br
M g (0)
O =C=O
OH
H 3O +
eth er
309
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
eth e r
R -L i
H 3O +
O
C
OH
C
R
R
14.8: Synthesis of Acetylenic Alcohols
R
C
+
H
C
NaNH2
R
C
C
N a+
+
pK a~ 3 6
p K a~ 2 6
R
C
C
H
NH3
+
H 3 C (H 2 C )H 2 C -L i
R
C
C
L i+
+
H 3 C (H 2 C )C H 3
pKa > 60
R
C
C
H
+
H 3 C H 2 C -M g B r
R
C
C
M g B r+
+
H 3C C H 3
pKa > 60
310
Recall from Chapter 9.6
_
R1 C C
THF
Na
+
+
R 1 C C C H 2R 2
R 2 -H 2 C -B r
ace tylid e an ion
+
N aB r
SN2
n e w C -C
b o n d fo rm ed
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
M gBr
+
+
R2
C
OH
TH F
O
R3
th e n H 3 O
R1 C
+
C
C
R3
R2
a ce ty le nic alco h o l
311
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
312
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-h exe ne
2-Phenyl-2-propanol
OH
CH3
CH3
313
14.11: Alkane Synthesis Using Organocopper Reagents
e th e r
2 C H 3L i
+
H 3C
C uI
_
Cu
L i+
+
L iI
H 3C
G ilm a n 's re a g e n t
(d im e th y lcu p ra te , d im e th ylc o p p e r lith iu m )
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.
314
Vinyl and aryl (but not acetylenic) cuprates
Br
4 L i (0) , e th e r
2
2
C uI
Li
C uLi
2
Br
2
Li
4 L i (0 ) , e th e r
C uI
C uLi
2
C uLi
THF
+
OTs
+
I
2
C uLi
THF
2
315
Reaction of cuprates with aryl and vinyl halides
H
H
(H 3 C ) 2 C u L i
I
H
Br
CH3
d ou b le b on d ge o m e try
is p re se rve d
H
(H 3 C H 2 C H 2 C ) 2 C u L i
C H 2C H 2C H 3
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
316
Generation and Reaction of Dihalocarbenes:
CHCl3
+
KOH
Cl2C:
+ H2O
+ KCl
dichlorocarbene
Carbenes react with alkenes to give cyclopropanes.
Cl
H
H
R
R
C H C l3, K O H
cis -alk ene
H
H
R
R
cis-cy clop rop an e
Br
H
R
R
H
tran s-a lke ne
Cl
C H B r3, K O H
Br
H
R
R
H
tran s-c yclo pro pa ne
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. 317
14.12: An Organozinc Reagent for Cyclopropane Synthesis
Simmons-Smith Reaction
ether
CH2I2
+
I-CH2-Zn-I = H2C:
Zn(Cu)
carbene
H
C H 2 I 2 , Z n (C u )
e th e r
H
The geometry of the alkene is preserved in the cyclopropanation
reaction.
H
R
H
R
C H 2 I 2 , Z n (C u )
e th e r
cis-a lke n e
H
R
R
H
tra n s-a lke n e
H
R
H
R
cis-cyclo p ro p a n e
C H 2 I 2 , Z n (C u )
e th e r
H
R
R
H
tra n s-cyclo p ro p a n e
318
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)
319