Download Organometallic Compounds

Organometallic Compounds
Chapter 15
Carbon Nucleophiles: Critical in making larger organic molecules.
Review some of the ones that we have talked about….
Cyanide ion: CN- + RX

RCN
 RCH2NH2
Synthetic thinking: Disconnect
+
NH2
CN-
Br
Acetylide anions:
strong base
RC
CH
RX
RC
RC
C:
CR
Synthetic Thinking: This offers many
opportunities provided you can work with the
two carbon straight chain segment.
Ph
X
Ph
Ph
Ph
Ph
Ph
Enolate anions:
O
or
base
O
X
O
O
OEt
H
RX
O
O
OEt
OEt
H
H
R
Try to see what factors promote the formation of the negative charge on the
carbon atoms: hybridization, resonance.
We examine two types of organometallics: RMgX, a Grignard
reagent, and RLi, an organolithium compound
Preparation
d-d+
dd+
Solvated by ether, aprotic solvent
Basicity
Recall that a carbanion, R3C:-, is a very strong base.
So also Grignards and alkyl lithiums.
Ethane, a gas.
Bottom Line: Grignards are destroyed by (weak) protic acids: amines,
alcohols, water, terminal alkynes, phenols, carboxylic acids. The
Grignard, RMgX, is converted to a Mg salt eventually and RH.
The liberation of RH can serve as a test for protic hydrogens.
Reactivity patterns
Recall the SN2 reaction where the alkyl group, R, is part of the electrophile.
Nucleophile
Nucleophile
Nu:- + R-X
Nu - R + X-
Electrophile
Forming the Grignard converts the R from
electrophile to a potential nucleophile. A wide
range of new reactions opens up with R as
nucleophile.
- +
RX + Mg  R-Mg-X
Electrophile
Electrostatic potential
maps.
+
-
Recall Reactions of Oxiranes
with Nucleophiles
Recall opening of oxirane with a strong, basic nucleophile.
CH3OO
H
H
H
H
OH
H
H
CH3
H3CO
CH3
The next slides recall the diversity of nucleophiles that may be used.
Observe that there is limited opportunity of creating new C-C bonds, welding
together two R groups. We seem to be somewhat lacking in simple
carbon based nucleophiles.
Recall Synthetic Applications
nucleophile
Only reaction with the acetylide
anion offers the means of making
a new C-C bond and a larger
molecule. Problem is that a
terminal alkyne is needed.
A Grignard has a reactive, negative carbon. Now examine reaction of
Grignard and oxirane ring.
Net results
Newly formed bond
The size of the alkyl group has increased by 2. Look at this alcohol to alcohol
sequence
R-OH  R-X  R-Mg-X  R-CH2-CH2-OH.
The functionality (OH) has remained at the end of the chain. We could make it
even longer by repeating the above sequence.
Note attack on less
hindered carbon
Now a substituted oxirane…
Newly formed bond
Synthesis Example
Retrosynthesize the following
OH
OH
O
CH2CH=CH2
CH2=CH - CH2MgBr
Recall reaction of a nucleophile with an
(oxirane) epoxide to give a
HO-CC-Nu pattern. Back side attack gives
anti opening.
Trans geometry suggests trying an
oxirane. What should the nucleophile
be?
The allyl group should be the
nucleophile. This is done by using a
Grignard (or Gilman).
Gilman Reagent (Lithium
diorganocopper Reagents)
Li
R-X
Preparation of Gilman Reagents
CuI
R-Li
R2CuLi
Gilman
Reactions of Gilman Reagent
Coupling Reaction Used to create new C – C
bonds..
Overall result. R-X + R’-X    R – R’
Necessary details
Li
As before:
Next step:
CuI
R-Li
R-X
R2CuLi
electrophile
R'-X
R2CuLi
R - R'
Restrictions on the process. Caution.
R group which goes
into Gilman may be
methyl, 1o (best not 2o
or 3o), allylic, vinylic
(unusual), aryl
Alkyl (not 3o), vinylic
nucleophile
Particularly useful, reaction with
vinyl halides to make an alkene.
trans
Note that the stereochemistry of the alkene is
retained.
Gilman and oxiranes
1. R2CuLi
HO
O
2. H2O, HCl
R
R of the Gilman reagent is the nucleophile, typical of organometallics.
Because in basic media (acid destroys Gilman) oxygen of oxirane can not
be protonated. Less hindered carbon of oxirane is attacked.
Synthetic Analysis
Similar to Grignard
analysis.
1. R2CuLi
HO
O
2. H2O, HCl
R
Newly formed bond.
Note its position
relative to the OH.
Example of Retrosynthetic Analysis
Design a synthesis using oxiranes
The oxirane ring could be
on either side of the OH.
Look at both possibilities.
Ph
Nucleophile can come in
on only one position of
oxirane, on the C to which
the OH should not be
attached…
OH
OH
OH
or
Ph
On the left, located here.
Open oxirane here.
Nucleophile makes this bond.
Ph
On the right, located here.
Open oxirane here.
Nucleophile makes this bond.
O
(PhCH2)2CuLi
2 synthetic routes
available
O
Ph
LiCu(CH2CH3)2
Synthesis Example
Carry out the following transformation in as many steps as needed.
Br
O
OCH3
O
target
OH
Br
O
OCH3
Remember
oxidation of a
secondary
alcohol can
produce a
ketone.
OCH3
Note pattern of a
nucleophile
(OCH3) then CC then OH. Use
an epoxide.
Epoxides
can come
from alkenes
via peracids.
Alkenes can
come from
halides via
E2.
Carbenes, :CH2
Preparation of simple carbenes
1.
carbene
2.
Mechanism of the a elimination.
Reactions of Carbenes, :CH2 (not for
synthesis)
Addition to double
bond.
Insertion into C-H bond
Formation of ylide (later)
liquid
Simmons Smith Reaction (for synthesis,
addition to alkenes to yield cyclopropanes)
CH2I2
+ Zn(Cu)

ICH2ZnI
Carbenoid, properties
similar to carbenes.
Electronic Structure
Electrons paired, singlet
Triplet and Singlet Methylene
Dominant form
in solution
Gas phase
CH2N2
singlet carbene
triplet carbene
Rotation can
occur around this
bond.
pi electrons
CH2
+
stereospecific
addition
diradical
non-stereospecific