Chapter 33: Diastereoselectivity

Diastereoselectivity begins by classifying amines according to their structure—primary, secondary, tertiary, and quaternary ammonium salts—and explains how nitrogen's lone pair availability directly influences their basicity and nucleophilicity. The basicity of amines is shaped by multiple factors including electronic effects from substituents, resonance phenomena, and solvation environment, which collectively determine their pKa values and reactivity profiles. The chapter then surveys major synthetic routes to amines, including ammonia alkylation, reduction of nitro compounds, reductive amination of carbonyl compounds, nitrile reduction, and the Gabriel synthesis, emphasizing strategies for achieving selective monoalkylation and avoiding problematic over-alkylation. A central focus addresses the reactions of amines with carbonyl electrophiles, where primary amines generate imines (Schiff bases) through nucleophilic addition and dehydration, while secondary amines form enamines that serve as versatile intermediates for carbon-carbon bond formation at alpha positions. The chapter details mechanisms of these transformations, including proton transfers and nucleophilic addition steps that illustrate nitrogen's dual role as nucleophile and lone-pair donor. Special attention is given to amide chemistry and related rearrangements, particularly the Hofmann and Curtius rearrangements, which convert amides and acyl azides into amines through skeletal rearrangement pathways. Aromatic amine chemistry receives substantial treatment, highlighting how resonance delocalization reduces basicity in aniline derivatives and facilitates their participation in electrophilic aromatic substitution and diazotization reactions. Diazonium salts emerge as versatile synthetic intermediates enabling substitution reactions including Sandmeyer transformations and applications in dye synthesis. The chapter integrates biochemical significance throughout, connecting amines to neurotransmitter function, alkaloid structures, and amino acid chemistry. Practical applications include quaternary ammonium salt formation for phase-transfer catalysis and surfactant chemistry, demonstrating amine utility across synthetic, analytical, and materials contexts.