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
Br

Acetylide anions:
strong base
RC

CN-

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

Enolate anions:
O

or
base

X
O

OEt
H

Ph

RX

OEt
H

OEt
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

Nu:- + R-X

Nu - R + X-

Nucleophile

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

HH

OH

H
CH3
H3CO

H
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
Note attack on less
even longer by repeating the above sequence.
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

R'-X

R2CuLi

electrophile
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

O

1. R2CuLi

HO

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.
O

1. R2CuLi

HO

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.
O

(PhCH2)2CuLi

Ph

On the right, located here.

Open oxirane here.
Nucleophile makes this bond.
2 synthetic routes
available
O

Ph

LiCu(CH2CH3)2

Synthesis Example
Carry out the following transformation in as many steps as needed.
Br

OCH3

target

OH

Br
O

OCH3

Remember
oxidation of a
secondary
alcohol can
produce a
ketone.

OCH3

Note pattern of a
nucleophile
(OCH3) then C-C
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 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