- General Reactivity of Carbonyl Compounds - C-O σ and (especially) π bonds are significantly polarized toward oxygen - Carbonyl carbon thus has significant δ+ character and is very electrophilic - Good nucleophiles attack carbonyl carbon with displacement of π electrons onto oxygen - Oxygen (δ-) is moderately Lewis basic and forms complexes with strong Lewis acids - Oxygen (δ-) is a weak Brønsted base (pKa of protonated carbonyls are -7 to -10) and is protonated by very strong acids and forms hydrogen bonds with water, alcohols, etc. - Protons on α-carbons are moderately acidic (pKa 20-25, similar to alkynes) and can be deprotonated ~completely by LiN(i-Pr)$_{2}$ and partially by NaOEt and KOt-Bu - Reactivity of Carbonyl Compounds as Electrophiles - Carbonyl carbon has significant δ+ character due to inductive effect and delocalization and is very electrophilic - Attack of nucleophiles at carbon shifts electrons of the highly polarized π bond onto the electronegative oxygen - Carbonyl groups are generally more electrophilic than alkyl halides and sulfonates (inductive withdrawal in σ bond only) - Adduct is an alkoxide and typically is "quenched" by addition of water or dilute acid to afford an alcohol product - Steric effects: large substituents slow attack due to steric hindrance and more crowded transition state (substituents pushed closer together as carbon goes from sp$^{2}$ (120°) to sp$^{3}$ (109.5°)) - Electronic effects: alkyl groups on the carbonyl carbon are electron donating (in addition to being sterically shielding) and reduce electrophilic reactivity (HCHO electrophilicity > aldehydes > ketones) - Electronic effects: π bonds (alkenyl and aryl groups) and heteroatoms (O, N, etc.) on the carbonyl carbon reduce electrophilic reactivity by delocalization of δ+ charge - Electronic effects: nearby electron-withdrawing groups increase electrophilicity by inductive effect (Cl$_{3}$CCHO electrophilicity > CH$_{3}$CHO) - Protonation of the carbonyl oxygen (or complexation to a Lewis acid) increases the electrophilicity by generating a carbocation (C$^{+}$ with OH or O-Met substituent)