Electrophilic Carbon

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Chapter: Organic Chemistry : Carbon-Carbon Bond Formation Between Carbon Nucleophiles and Carbon Electrophiles

Carbon-centered electrophiles are compounds or intermediates which are electron poor and thus capable of accepting electrons from electron donors.


Carbon-centered electrophiles are compounds or intermediates which are electron poor and thus capable of accepting electrons from electron donors. To be an electron acceptor, an electrophile must have an unfilled orbital on carbon avail-able for overlap with a filled orbital of the donor. Unfilled atomic p orbitals or antibonding orbitals (both σ and π ) are the most common types of acceptor orbitals. The most common carbon electrophiles fall into four major categories:

(a) Cationic carbon electrophiles are the most reactive because of the positive charge they carry. They can, however, have a variety of structures depending on the hybridization of the carbon acceptor. Trialkyloxonium tetrafluoroborates (Meerwein salts) R3O+ BF4, for example, are sp3-hybridized carbon elec-trophiles and are extremely reactive toward nucleophiles. The acceptor orbital is an antibonding C–O σ orbital which is low in energy because of the positive charge on oxygen.

Triphenylmethyl (trityl) tetrafluoroborate, on the other hand, is sp2 hybridized but it is also extremely reactive toward electron donors. The acceptor orbital of the trityl cation is an unfilled 2p atomic orbital on the charged carbon. These carbon electrophiles are isolable compounds, but they are extremely reactive with any sort of electron donor (H2O vapor is a common culprit).

Many other cationic carbon electrophiles cannot be isolated but can be gen-erated insitu in a reaction mixture by Bronsted or Lewis acid–base reactions. In the presence of Bronsted acids, carbonyl compounds are protonated and produce positively charged oxonium ions. Compared to the carbonyl compound itself, the π orbitals of oxonium ions are much stronger electron acceptors.

Protonation of the carbonyl group is an equilibrium process, and the extent of protonation (the position of the protonation equilibrium) is dictated by the pKa’s of the Bronsted acid and the oxonium ion. While this equilibrium usually lies far to the left, the reactivity of the oxonium ion is often sufficiently great that only small amounts of the oxonium ion are needed to react effectively with the electron donor.

Addition of a strong Lewis acid such as TiCl4, BF3, or SnCl4 to a carbonyl compound is another common method to produce a very powerful cationic elec-trophile in solution. Complexation between the Lewis acid and the lone pairs of electrons on the carbonyl oxygen give a species which, although formally neutral, behaves as a cationic carbon electrophile in the same fashion as a proto-nated carbonyl group. These are strong electrophiles that react with many types of nucleophiles. While aldehydes and ketones are common carbonyl compo-nents which are activated with Lewis acids, esters and amides also yield strongly electrophilic species with Lewis acids.

(b) Aliphatic compounds with good leaving groups attached to primary or secondary carbon atoms are very commonly used as carbon electrophiles. The leaving group is an electronegative group attached by a polarized σ bond.

The bond polarity makes the carbon atom electron deficient and capable of accept-ing electrons from carbon electron donors (carbon-centered nucleophiles) into the σ antibonding orbital. Population of the σ orbital by electron donation weakens the bond to the leaving group. Ultimately the leaving group is cleaved from the molecule and retains the pair of electrons from the connecting bond. Examples of such compounds include alkyl halides, alkyl sulfonates, and alkyl sulfates.

The electrophilicity of such compounds is largely related to the leaving ability of the leaving group. The leaving ability of a group is in turn related to (1) its bond strength to carbon and (2) its ability to accept the bonded pair of elec-trons and become electron rich (most often negatively charged). Leaving abilities range from excellent (triflate) to moderate (chloride). The electrophilicity of the acceptor molecule thus can be adjusted by changing the leaving group.

(c) Carbonyl compounds are very common carbon electrophiles by virtue of the polarized carbon–oxygen π bond. Electron donation into the π orbital of the carbonyl carbon breaks the C–O π bond and produces a tetrahedral adduct which can then proceed to products.

This is a very general process for carbonyl compounds; however, the elec-trophilic reactivity of the carbonyl group is very dependent on the groups attached to it. The reactivity is ranked in the following order:

Electron-withdrawing groups (Cl, RCO2) increase the electrophilicity while resonance-donating groups –OR, –NR2 decrease the reactivity toward electron donors. Steric effects are also a significant influence on carbonyl reactivity. The trigonal carbonyl reactant goes to a more crowded tetrahedral intermediate upon addition of the nucleophile; thus bulky groups attached to the carbonyl carbon lead to more crowded transition states and result in much slower addition reactions. This steric rationale is one explanation for the greater reactivity of aldehydes over ketones. Extremely sterically hindered ketones such as di-tert-butyl ketone undergo carbonyl addition by nucleophiles at negligible rates for most nucleophiles.

(d) α,β-Unsaturated carbonyl compounds can act as electrophiles under certain conditions and are bidentate in that both the carbonyl carbon and the β carbon are electron deficient. Thus nucleophiles can attack at either position.

The regioselectivity of nucleophilic addition is a function of the type of nucleophile employed and in many instances can be controlled to give Michael addition to the β carbon.

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