What are Carbon Nucleophiles?

We are aware that carbon belongs to group IV and hence does not possess any lone pair of electrons. Implying that neutral carbon is not a nucleophile then how is carbon going to be nucleophilic? The answer to this is that when a carbon atom is attached to a metal (can be seen in the case of organometallic compounds), the metal atom develops a partial positive charge and carbon develops a partial negative charge, hence making carbon nucleophilic.

Key Takeaways     

• What makes carbons nucleophilic?
• What compounds possess a nucleophilic carbon? (classification)
• Significance of carbon nucleophiles.
• Some important reactions involving carbon nucleophiles.

Nucleophiles

A nucleophile refers to an electron rich species which has an affinity towards any positively charged species (i.e., electrophiles) and is able to form bonds readily with the electrophile.

Carbon nucleophiles can be observed in two types of compounds- in organometallic compounds and in enols.

Enols

We know that a carbonyl compound (aldehydes/ketones) undergo tautomerisation to give enol-enolate ion.

Basically in tautomerisation of carbonyl compounds, the alpha hydrogen present on the alpha carbon atom migrates to the oxygen of the carbonyl group which leads the migration of the pi-bond to the alpha carbon. 

This is specifically referred to as the keto-enol automerization- keto form is when the alpha hydrogen is bonded to the alpha carbon and the enol form when the alpha hydrogen is bonded to the carbonyl oxygen atom (along with the migration of the pi-bond).

Although both these forms exist in a kind of equilibrium, the keto form is most stable. However, this is of significance to us because a number of reactions are possible when the compound is in the enol form.

During the conversion of the carbonyl compound from keto to enol / enolate form, it results in the formation of an intermediate wherein the alpha carbon acts as a nucleophile. This nucleophile in the presence of haloalkanes gets alkylated.  Enols also participate in condensation reactions involving carbonyl compounds like the aldol and Claisen condensation reactions.

NOTE: Enol isomers are relatively extremely acidic in comparison with the keto isomers.

Organometallic compounds

Organometallic compounds consist of a carbon of an organic molecule bound to a metal. The metal can be alkali metal, alkaline earth metal, transition metal, and post transition metal, lanthanide, actinide, semimetal, metalloid (like elements boron, silicon, arsenic, and selenium). Since a metal is going to be more electropositive than carbon, carbon will develop a partial negative charge at its end and therefore participates as a nucleophile in a number of reactions!

Vitamin b12 (methylcobaltamine) is an example of naturally occurring organometallic compound. This has cobalt as the metal atom bonded to carbon of methyl group. A lot more compounds which are found in biological systems can be found and come under naturally occurring organometallic compounds like chlorophyll (Magnesium attached to four porphyrin rings), hemoglobin (globin chains attached to iron molecule), etc.

Some organometallic compounds are

Ferrocene

Trimethyl boron $\text{B}{\left({\text{CH}}_{\text{3}}\right)}_{\text{3}}$

Prussian blue $F{e}_4{\left[Fe{\left(CN\right)}_6\right]}_3$ (Ferric ferrocyanide/potassium hexacyanoferrate/sodium hexacyanoferrate)

The first organometallic compound to be artificially synthesized is called Zeise’s salt which is $K\left[PtC{l}_3\left(C_2{H}_4\right)\right]\cdot H_{2}O$- potassium trischloroethene platinate(II). This compound is of significance because it was seen that it powerfully inhibits cyclooxygenase (COX) enzymes, and it displays low cytotoxicity against cancer cells.

Grignard reagents

There are several such examples for organometallic compounds but the ones which are commonly used and most studied are organ magnesium compounds that are collectively referred to as the ‘Grignard reagents’. In this class of compounds, magnesium halide is bonded to an alkyl/aryl/allyl/vinyl carbon.

Grignard reagents are widely used in organic chemistry for the preparation of a number of reactions as it facilitates formation of carbon-carbon bonds.

$R-MgBr$ is the general chemical formula of a Grignard reagent. This compound got its name from the scientist who first synthesised it, Victor Grignard.

The salient reaction in which it participates is the Grignard reaction. Here, the Grignard reagent reacts with a carbonyl compound to result in the formation of an alcohol with higher number of carbons.

The salient reaction in which it participates is the Grignard reaction. Here, the Grignard reagent reacts with a carbonyl compound to result in the formation of an alcohol with higher number of carbons.

NOTE: The Grignard reaction is NOT to be confused with the reaction between an organic halide and magnesium atom. This only generates a Grignard reagent but the Grignard reagent focuses on reaction between the reagent with an aldehyde or ketone.

In the above reaction, the carbon of the R group in the reagent is nucleophilic and the carbon of the carbonyl groups is electrophilic. They form an adduct compound which on hydrolysis yields a higher alcohol.

Classifying Carbon Nucleophiles

Another classification describes 3 subclasses of carbon nucleophiles-

• Grignard reagents and organolithium compounds (organometallic compounds)
• Hydrogen cyanide and potassium cyanide
• Phosphonate ester carbanions and phosphorus ylides.

Let us see each of these classes of compounds in detail.

Organometallic compounds

As seen in the previous section. Organometallic compounds possess a nucleophilic carbon and we saw what a Grignard reagent is.

The other compounds of significance are organolithium compounds. The metal is lithium and it is bonded to an organic carbon atom. They are of significance in organic synthesis (used for nucleophilic addition reactions to synthesize organic molecules).

Their application in the industry is that they are used as an initiator for the polymerization reaction to yield elastomers. The $C-Li$ bond is highly ionic.

These reagents are able to act as nucleophiles and facilitate $S_{N}2$ reactions with alkyl or allyl halides.

Cyanide ions

Cyanide ions have a carbon triply bonded to a nitrogen atom $:C\equiv N$ with a lone pair of electrons on carbon that renders the molecule as a nucleophile. Cyanide ions can either be obtained from hydrogen cyanide or from potassium cyanide. Cyanide ions participate in a number of organic reactions, too.

Carbonyl compounds undergo nucleophilic addition of cyanide ions result in the formation of cyanohydrins (a condensation product) which can further undergo subsequent conversion reactions to yield carboxylic acids, amines, etc..,

Ylides

One of the popular reactions in organic chemistry is the Wittig reaction. Wittig reaction is facilitated by phosphonium ylides/phosphines/phosphonate carbanions.

Phosphorus analogs of amines are called phosphines ($:P{R}_3$) and they react with alkyl halides to produce phosphorus salts called phosphorus ylides which are stable salts. The phosphorus in this compound has a positive charge which pulls the electrons towards itself enabling easy deprotonation of the methyl group present. As a result of this, the methyl carbon becomes nucleophilic.

Practice Question

Q. Where can we see applications for carbon nucleophiles which are of significance?

Answer-  We have established the fact that reactions involving formation of carbon-carbon bonds are easily achieved using carbon nucleophiles. Enunciating this further, we can say that in biochemistry and molecular biology, it sees utmost significance because proteins, enzymes, nucleic acids (DNA & RNA), amine acids, fatty acids and all biomolecules require carbon-carbon bond formation for the carbon backbone and hence their synthesis is facilitated by carbon nucleophilic addition reactions with some precursors.

Context and Applications

This topic is significant in the professional exams for both undergraduate and graduate courses, especially for

• B.Sc in Chemistry
• M.Sc in Chemistry