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 RX
RC CH RC C: RC CR

Synthetic Thinking: This offers many X

opportunities provided you can work with the
Ph
two carbon straight chain segment. Ph
Ph
Ph
Ph
Ph
Enolate anions: or
X
O O base O O RX O O

OEt
OEt OEt
H 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
-+

-
+

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 RX + Mg  R-Mg-X
range of new reactions opens up with R as
nucleophile. Electrophile

Electrostatic potential
maps.

+ -
 Recall Reactions of Oxiranes
with Nucleophiles
Recall opening of oxirane with a strong, basic nucleophile.
CH3O-
O OH
HH
H H
H CH3 H
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

CH2CH=CH2

CH2=CH - CH2MgBr

Recall reaction of a nucleophile with an

(oxirane) epoxide to give a HO-C-
C-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 CuI
R-X R-Li R2CuLi
Preparation of Gilman Reagents 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 CuI
R-X R-Li R2CuLi
As before:
electrophile
R'-X
Next step: R2CuLi R - R'

Restrictions on the process. Caution.

R group which goes Alkyl (not 3o), vinylic

into Gilman may be
methyl, 1o (best not 2o
or 3o), allylic, vinylic
(unusual), aryl 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 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

Newly formed bond.

Note its position
relative to the OH.
 Example of Retrosynthetic Analysis
Design a synthesis using oxiranes Nucleophile can come in
The oxirane ring could be OH on only one position of
on either side of the OH. oxirane, on the C to which
Look at both possibilities. Ph the OH should not be
attached…
OH
OH
or
Ph
Ph
On the left, located here.
Open oxirane here. On the right, located here.
Nucleophile makes this bond. Open oxirane here.
Nucleophile makes this bond.
O

(PhCH2)2CuLi 2 synthetic routes

available
O

LiCu(CH2CH3)2
Ph
 Synthesis Example
Carry out the following transformation in as many steps as needed.
Br O

OCH3

O
OH
target Br

O
OCH3
OCH3

Remember Note pattern of a Epoxides Alkenes can

oxidation of a nucleophile can come come from
secondary (OCH3) then C-C from alkenes halides via
alcohol can then OH. Use via peracids. E2.
produce a an epoxide.
ketone.
 Carbenes, :CH2
Preparation of simple carbenes
1.

carbene

2.

Mechanism of the  elimination.

 Reactions of Carbenes, :CH2 (not for
synthesis)

Addition to double
bond.
liquid

Insertion into C-H bond

Formation of ylide (later)

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
Gas phase
in solution

CH2N2

Rotation can
singlet carbene triplet carbene occur around this
bond.

pi electrons

CH2
+

stereospecific
addition diradical
non-stereospecific