CHEM-332

Rahman S. Z. Saleem
Department of Chemistry & Chemical Engineering, SBASSE
Lahore University of Management Sciences

Lecture

08
Oct 01, 2019
 Using Organometallic Reagents to Form C-C Bonds

Recent examples of the reactions

Why are organometallics (OMs) nucleophilic?

How OMs are prepared?
Which type of carbonyl compounds OM reagents react with?
What kind of molecules can be prepared using these type of reactions.
 Using Organometallic Reagents to Form C-C Bonds

Electronegativity difference determines the polarity of the covalent bond

The difference in the electronegativity of the metal & the carbon atom is the key to determine
the reactivity of OM reagents towards electrophilic compounds. Greater the difference in the
electronegativity, faster would be the reaction.
 Using Organometallic Reagents to Form C-C Bonds

Remember, lower is the electronegativity of an atom, lower would be its orbital energy.
The energy of filled Li-C orbital is closer to that of sp3-orbital of C-atom & thus C makes more
contribution to the Li-C sigma bond. Li-C sigma bond thus has a larger coefficient on C.
Using Organometallic Reagents to Form C-C Bonds

These reagents can be prepared by a number of ways:

Oxidative insertion of Mg into alkyl halides

Oxidative insertion of Li into alkyl halides
Deprotonation of alkynes
Ortholithiation of functionalized benzene rings
Halogen–metal exchange
Transmetallation
 How to Prepare Grignard’s Reagents

Oxidative addition (alkyl halide + Mg turnings)

 How to Prepare Grignard’s Reagents

Mechanism unclear but overall it involves an insertion of Mg into the new carbon–halogen bond

way of writing the mechanism

• Reaction probably happens on the metal surface.

• Initiation at metal surface might be needed.
• Complex between the metal and the ether solvent
 How to Prepare Grignard’s Reagents - Mechanism

Another proposed mechanism of formation of a Grignard reagent using radical intermediates.

There is one major difference, however: Grignard formation does not involve a radical chain
mechanism. It is a non-chain radical reaction.

At higher conc. Grignard’s reagent may predominately exist as dialkyl species

Schlenk equilibrium

In the formation of Grignard reagent, the polarity of carbon attached to the halide group is
reversed. This reversal in polarity is called as umpolung or polarity inversion.
 Cyanide Type Umpolung
The cyanide ion is unusual in that a C triply bonded to a N would be expected to have a (+)
polarity due to the higher electronegativity of the N. Yet, the -ve charge of the CN ion is localized
on the carbon. This chemical uncertainty results in umpolung in many reactions where cyanide
is involved, for example benzoin condensation.
 How to Prepare Organolithium Reagents?
Organolithium compounds may be made by a similar oxidative insertion reaction from lithium
metal and alkyl halides. Each inserting reaction requires two atoms of lithium.

As with Grignard formation, there is really very little limit on the types of organolithium that can
be made this way.
Some Grignard & organolithium commercially available
reagents

The preparation and the use of organometallics could be risky and

precautions must be taken when using these reagents.

What makes their use risky?

 Organometallics as bases

Moisture sensitive

Equilibrium is vastly to left (What does that mean?)

These reagents will react with anything that is acidic

 Making organometallics by Deprotonating Alkynes
Alkynes with terminal C-H bond are most acidic among hydrocarbons due to sp-hybridization
More Reactions of Organometallics
More Reactions of Organometallics
Making Organometallics by Deprotonating Aromatic Rings:
Ortholithiation
Order of acidity sp- > sp2- > sp3-

Need an ortho-FG
 Halogen-Metal Exchange to Form Organolithium Compounds

The reaction works because the organolithium that is formed (PhLi) is less basic (more stable)
than the organolithium we started with (BuLi).
 Halogen-Metal Exchange to Form Organolithium Compounds

Iodides, bromides, and chlorides can all be used, but the reactions are fastest with iodides and bromides. In
fact, halogen–metal exchange can be so fast that, at very low temperature (–100 °C and below), it is even
occasionally possible to use compounds containing functional groups that would otherwise react with
organolithiums, such as esters and nitro compounds.
Halogen-Metal Exchange: Example
 Transmetallation

A type of reaction that involves transfer of a group from one metal to another.

M1-X + M2-R' → M1-R' + M2-X

More electropositive metal can be replaced with less electropositive metal

Li 1.0 Mg 1.2 Ce 1.1

The more electropositive lithium goes into solution as an ionic salt, while the less
electropositive metal (magnesium and cerium in these examples) takes over the alkyl group.

Unwanted side reactions due to high reactivity of Li can be avoided using Ce

 Organocerium Compounds Act as Nucleophile Rather than a
Base
RLi & RMgX can remove acidic protons rather than add to the carbonyl group.
Ethynylcerium dichloride (HC≡CCeCl2), being a better nucleophile rather than a base, reacts with
the ketone to give an 85% yield of the alcohol.

Sometimes transmetallation is used to decrease nucleophilicity