Chapter 6: Ketones & Aldehydes: Nucleophilic Addition

The discussion begins with reliable methods for preparing these compounds, such as the selective oxidation of primary alcohols into aldehydes using pyridinium chlorochromate (PCC) and the oxidation of secondary alcohols into ketones using reagents like sodium dichromate or the Jones reagent. Additionally, the sources highlight ozonolysis as a vital method for cleaving alkenes to yield carbonyl-containing products. The reactivity of ketones and aldehydes is largely dictated by the electrophilic nature of the carbonyl carbon, which carries a partial positive charge due to both induction and resonance, making it an ideal target for a wide array of nucleophiles. When reacting with hydrogen nucleophiles like sodium borohydride or lithium aluminum hydride, these compounds undergo reduction to form alcohols, though the stronger lithium reagent requires a separate aqueous workup step. The sources detail how oxygen-based nucleophiles produce acetals and hemiacetals, emphasizing their role as reversible protecting groups that shield the carbonyl from unwanted reactions during complex syntheses. Similarly, sulfur nucleophiles create thioacetals, which serve as intermediates in the complete reduction of carbonyls to alkanes via Raney nickel desulfurization. Nitrogen-based reactions are thoroughly categorized, covering the formation of imines from primary amines, enamines from secondary amines, and the specialized production of oximes and hydrazones. Hydrazones are specifically noted for their involvement in the Wolff-Kishner reduction, providing a basic-condition alternative for transforming a ketone into an alkane. The synthesis of complex molecules is further enabled by carbon nucleophiles; Grignard reagents are utilized to form new carbon-carbon bonds resulting in substituted alcohols, while the Wittig reaction employs phosphorus ylides to convert carbonyls into alkenes, and sulfur ylides are used to generate epoxides. The chapter concludes with the Baeyer-Villiger oxidation, where peroxy acids like meta-chloroperoxybenzoic acid (MCPBA) insert an oxygen atom adjacent to the carbonyl. This unique rearrangement follows a migratory aptitude where hydrogen or more substituted alkyl groups move to form esters or lactones, providing a powerful tool for molecular modification.