Chapter 9: Using Organometallic Reagents to Make C–C Bonds

The foundation rests on understanding how the carbon-metal bond, formed between carbon and electropositive metals such as lithium or magnesium, generates nucleophilic character at the carbon atom. Through molecular orbital analysis, the text demonstrates how this polarity renders the carbon atom carbanion-like, enabling it to function as a strong nucleophile capable of attacking electrophilic sites, most notably carbonyl groups. The chapter details multiple synthetic routes to organometallics: oxidative insertion of metals into alkyl halides, deprotonation of terminal alkynes using strong bases, halogen-metal exchange reactions, and transmetallation to generate less reactive organozinc derivatives. Practical considerations including solvent selection, metal surface activation, and reaction mechanisms involving radical intermediates receive thorough treatment. Once prepared, these nucleophilic species undergo reactions with diverse electrophiles to construct target molecules. Carbon dioxide addition yields carboxylic acids through one-carbon homologation, formaldehyde produces primary alcohols, while aldehydes and ketones generate secondary and tertiary alcohols respectively, with multiple synthetic routes often available for a single target. The text emphasizes synthetic flexibility and strategic choice based on reagent economics and operational practicality. Oxidation chemistry using chromium-based reagents such as pyridinium chlorochromate and pyridinium dichromate enables conversion of alcohols to aldehydes, ketones, or carboxylic acids, facilitating movement across oxidation states. Representative syntheses of biologically active natural products and pharmaceuticals, including a juvenile hormone and fungicidal compounds, illustrate practical application. The chapter establishes organometallics as foundational synthetic methodology, demonstrating how these reagents integrated with carbonyl chemistry and oxidation-reduction transformations enable efficient construction of complex organic molecules and prepare students for advanced synthetic strategies.