Overview
This lecture introduces the core concepts of organic synthesis, focusing on using previously learned reactions and reagents to design step-by-step pathways from starting materials to desired products. Strategies, key reactions, and practical problem-solving techniques are reviewed to build confidence in tackling synthesis questions.
Introduction to Synthesis
- Synthesis in organic chemistry is about constructing organic compounds from specific precursors.
- Mastery of reagents and reaction patterns from chapters 7–10 is critical for success.
- Synthesis problems require applying multiple reactions in sequence to transform starting materials into products.
Review of Core Reactions and Reagents
- Substitution and elimination reactions with alkyl halides can create or remove functional groups (e.g., converting alkyl halides to alcohols, nitriles, esters).
- Addition reactions to alkenes and alkynes introduce new groups (halogens, alcohols, hydrogen, etc.) across double or triple bonds.
- Useful techniques include adding halogens via NBS or Br2, converting alkanes to alkyl halides, and alternating elimination/addition to move functional groups along carbon chains.
- Carbon-carbon bond formation uses terminal alkyne alkylation; ozonolysis is used to cleave double bonds and shorten carbon skeletons.
Key Synthesis Techniques
- To create or modify carbon skeletons, use alkylation (to extend) and ozonolysis (to cleave).
- Moving functional groups/pi bonds is often achieved by alternating elimination and addition reactions.
- For complex problems, work backwards from the product using retrosynthetic analysis.
Practice: One-Step and Multi-Step Synthesis
- Identify reagents for specific single-step transformations (e.g., HBr/peroxides for anti-Markovnikov addition, O3/DMS for ozonolysis).
- Multi-step synthesis combines core techniques: e.g., convert alkenes to alkynes by halogenation then double elimination, move leaving groups via elimination and Markovnikov addition, construct larger chains by repeated alkylation of terminal alkynes.
- Double elimination of vicinal/geminal dihalides forms alkynes; acid-catalyzed hydration of alkynes yields methyl ketones.
- Use Lindlar’s catalyst for cis-alkene formation from alkynes.
Study and Practice Strategies
- First focus on mastering one-step synthesis before attempting multi-step pathways.
- Practice consistently with textbook problems and blocking out reagent tables for self-testing.
- Recognize that there is often more than one valid pathway in synthesis problems.
Key Terms & Definitions
- Synthesis — Designing a series of chemical reactions to produce a target molecule from specified starting materials.
- Retrosynthesis — Problem-solving approach where you analyze the product and work backwards to the starting material.
- Elimination Reaction — Removes atoms/groups from a molecule, typically forming a double or triple bond.
- Addition Reaction — Atoms or groups add across a double or triple bond.
- Markovnikov/Anti-Markovnikov Rule — Orientation of addition of HX to alkenes or alkynes (most/least substituted carbon).
- Ozonolysis — Cleavage of alkenes/alkynes using ozone to form carbonyl compounds.
- Alkylation — Addition of an alkyl group to a molecule.
- Hydrogenation — Addition of hydrogen to double/triple bonds, often using a metal catalyst.
Action Items / Next Steps
- Practice one-step synthesis using provided reaction tables and textbook problems.
- Attempt multi-step synthesis problems as comfort with reagents increases.
- Complete assigned synthesis problem "c" and "e" from the lecture for additional practice.