Organic chemistry
Retrosynthetic analysis
Retrosynthesis plans a synthesis backward from a target by identifying strategic bond disconnections and mapping the resulting synthons to real reagents.
IntuitionIntuition: plan backward from the target
A difficult molecule is rarely assembled in one leap. Imagine cutting a strategically chosen bond in the target and asking which simpler pieces could be joined to make it. Repeat until the pieces are available or inexpensive starting materials.
SchoolSchool level: functional groups guide choices
Definition:
A conceptual bond cleavage that transforms a target into simpler precursors. A retrosynthetic arrow (⇒) means “could be made from,” not a forward reaction arrow.
Functional-group interconversion (FGI) changes a functional group without changing the carbon skeleton—for example, oxidizing a primary alcohol to an aldehyde. FGI can expose a more useful disconnection.
| Target motif | Retrosynthetic idea | Forward reaction |
|---|---|---|
| β-Hydroxy carbonyl | C–C cut into enolate and carbonyl synthons | Aldol addition |
| Secondary or tertiary alcohol | Disconnect a C–C bond beside C–OH | Organometallic addition to a carbonyl |
UndergraduateUniversity: synthons and synthetic equivalents
A synthon is an idealized charged fragment used to reason about a disconnection; it is not necessarily an isolable species. Its synthetic equivalent is a real reagent that supplies the same reactivity. In an aldol disconnection, the nucleophilic synthon is represented in practice by an enolate, while an aldehyde or ketone supplies the electrophilic carbonyl carbon.
Example: Choose an aldol disconnection
A target contains a β-hydroxy ketone unit. Identify the bond-forming reaction and its two main precursors.
Solution
Disconnect the bond between the α carbon of the ketone and the β carbon bearing OH. The forward option is aldol addition: form the ketone enolate, then add an aldehyde carbonyl electrophile; assess self-condensation and regioselectivity before choosing conditions.
UndergraduateUniversity: rank complete routes
A good disconnection reduces structural complexity while preserving useful functional groups and stereochemistry. Route ranking also weighs step count, yield, selectivity, safety, cost, scalability, and availability of starting materials; shortest is not automatically best.
References
- The Logic of Chemical Synthesis · E. J. Corey, Xue-Min Cheng, 1989
- Organic Chemistry (2nd ed.) · Jonathan Clayden, Nick Greeves, Stuart Warren, 2012