Retrosynthesis
Planning a synthesis by working backward from the target molecule.
Planning a synthesis by working backward from the target molecule.
Retrosynthesis is a planning method in which a target molecule is worked backward to find simpler starting materials. The chemist makes a disconnection at a strategic bond, which corresponds to a reverse reaction, and the resulting pieces are called synthons, which are then matched to real reagents. The process repeats until the fragments correspond to commercially available compounds. The method was developed by E. J. Corey, who received the Nobel Prize in Chemistry in 1990, and it greatly improved the design of complex syntheses.
Key ideas: Work backwards from the target: disconnect bonds at functional groups to simpler synthons, then match with real reagents (synthetic equivalents). Typical disconnections: C-C next to carbonyl (aldol, enolate alkylation), alcohol C-C (Grignard), amine C-N (reductive amination). Prefer convergent routes, few steps, and high-yielding reactions; overall yield equals product of step yields (five steps at 80 percent gives 33 percent).
Common mistakes and connections: Students forget compatibility of functional groups with later reagents, or that overall yield drops fast. Another error is writing a disconnection that produces unrealistic synthons. Use functional group interconversion and protecting groups. Links to Grignard, aldol, Diels-Alder and protecting groups.
A tertiary alcohol can be disconnected into a ketone and a Grignard reagent, which are simple precursors.
Planning a synthesis by working backward from the target molecule.
Retrosynthesis is a advanced topic in Organic Chemistry. It builds on beginner and intermediate topics, so review those first if needed.
Study these earlier topics in Organic Chemistry first: Natural and Synthetic Rubber, Biodegradable Polymers, Organic Reaction Mechanisms.
The next topics in Organic Chemistry are Protecting Groups and Diels-Alder Reaction.
Yes. The interactive lesson includes a self-check question on Retrosynthesis, and the Organic Chemistry quiz draws on every topic in this area.
Retrosynthesis is topic 109 of 148 in Organic Chemistry.