Nucleophilic addition to carbonyls is one of the main reactions of carbonyls. This reaction involves a nucleophilic attack on a carbonyl carbon either following or preceding a proton transfer step. The nucleophile can be a wide range of compounds with oxygen, nitrogen, sulfur, carbon, or hydrogen as the nucleophilic atom.
A carbonyl is a functional group in which carbon atoms are double bonded to oxygen atoms. Carbonyls are the class of compounds that includes aldehydes and ketones, among others. An aldehyde is an organic compound that contains a carbonyl group (C=O) bound to one alkyl (−R) fragment and one hydrogen atom, with RC(=O)H or R−CHO stoichiometry. A ketone is an organic compound that contains a carbonyl group (C=O) bound to two alkyl (−R) fragments (which can be the same, R and R, or different, R and R′), with RC(=O)R′ or RCOR′ stoichiometry. The carbonyl bond is polarized because of the electronegativity differences between the carbon and the oxygen. The oxygen, being more electronegative, is the negative end of the dipole because it holds more of the shared electrons, while the carbon is the positive end of the dipole.
Carbonyl Bond
The carbonyl bond is polarized because of the electronegativity differences between the carbon and the oxygen. The oxygen is the negative end of the dipole, while the carbon is the positive end.
Because of the dipole of the carbonyl bond, a strong nucleophile may add to the electrophilic carbon via nucleophilic addition. A nucleophilic addition reaction is a reaction where an electron-rich reactant (a nucleophile) reacts with an electron-deficient part of a compound. This reaction breaks one π bond (pi bond) while generating two new σ bonds (sigma bonds). A nucleophile (or Lewis base) is a molecule or ion rich in electrons that donates a pair of electrons that forms a covalent bond. An electrophile (or Lewis acid) is a molecule or ion that accepts electrons to form a covalent bond.
The addition of an anionic nucleophile to a carbonyl will cause the π bond between the carbon and the oxygen to break. The shared electrons move to the oxygen, and an alkoxide intermediate forms. An alkoxide is the conjugate base of an alcohol that consists of an organic group bonded to a negatively charged oxygen atom. Protonation (or addition of a H+ cation) of the alkoxide intermediate will generate the final alcohol product.
Basic Nucleophilic Addition
The nucleophilic attack of an anion on a carbonyl will produce an alcohol through an alkoxide intermediate that will convert to an alcohol with an acidic workup.
If the nucleophile is neutral rather than anionic, the carbonyl needs to be activated before the nucleophile can attack it. A carbonyl is activated when the oxygen of the carbonyl is protonated by an acid catalyst (a H+ cation) and the oxygen becomes positive. The neutral nucleophile then adds to the more positive carbon, breaking the π bond between the carbon and the oxygen. This results in the shared electrons moving to the oxygen. The oxygen is already protonated; therefore, no alkoxide intermediate is formed. The addition of the nucleophile and the breaking of the π bond yield the final alcohol product after the nucleophile is deprotonated.
Acid-Catalyzed Nucleophilic Addition
An acid-catalyzed nucleophilic attack is needed when the nucleophile is neutral. An alcohol is generated from this reaction.
Aldehydes tend to be more reactive toward nucleophiles because of the steric and electronic effects of the substituents. A steric effect is a nonbonding interaction that occurs through 3-D space and changes the reactivity of an ion or molecule because of size, arrangement, and spatial factors. Larger or bulkier substituents attached to the carbonyl group, such as a tert-butyl group, make it more difficult for the nucleophile to add to the carbon. An electronic effect is an influence on the reactivity of a group based on movement or location of electrons in a bond. Groups such as an alkyl or a phenyl ring that make the carbon in the carbonyl group less electrophilic make it less reactive toward nucleophiles. In addition to compounds with oxygen, compounds with nitrogen, sulfur, carbon, or hydrogen can be used as the nucleophilic atom in nucleophilic addition reactions.
