Chemoselectivity
High-Yield Summary
- Chemoselectivity is the preferential reaction of one functional group over others when a molecule has multiple reactive sites.
- Two key MCAT reactive sites: the carbonyl carbon (electrophilic, from O's electron withdrawal) and the substrate carbon in substitution reactions (SN1/SN2 site).
- General priority rule: the most oxidized functional group is often the most reactive site for oxidation, reduction, or nucleophilic attack — a default, not absolute.
- Steric hindrance can slow/block reactivity at a site, and protecting groups temporarily mask a reactive group so it survives later reaction steps, then get removed to restore it.
- Worked pattern: protect the more-reactive group → run the reaction on the target group → deprotect to restore the original functional group.
Framework for Analyzing Reaction Problems
- 1Identify all functional groups present in the molecule.
- 2Analyze the reagents — is each an oxidizing agent, reducing agent, nucleophile, or electrophile?
- 3Identify the most reactive functional group under the given conditions (most-oxidized-group priority rule).
- 4Determine the first step of the reaction — many reactions proceed sequentially.
- 5Consider stereospecificity/stereoselectivity — does the reaction favor one stereoisomer, cause racemization, or retain configuration?
Key Terms
- Chemoselectivity
- The preferential reaction of one functional group over others present in the same molecule.
- Steric hindrance (as a control tool)
- Physical crowding around a reactive site that chemists exploit to slow/block reactivity there, favoring a different site.
- Protecting group
- Temporary mask on a reactive functional group so it survives later reaction conditions unchanged; removed afterward to restore the original group.
- Cyclic acetal
- Product of protecting a ketone/aldehyde with a diol (e.g. ethylene glycol) + acid catalyst (TsOH); shields the carbonyl from reduction/nucleophilic attack until hydrolyzed back.
Common MCAT Trap
- 'Most oxidized reacts first' is a default, not a law — steric hindrance or a protecting group can override it, so always check the reagents/conditions given.
- A protecting group changes reactivity, not identity — the ketone masked as an acetal is still 'the same functional group' conceptually, just temporarily unreactive.
- Don't forget the deprotection step — a synthesis question showing a protected group partway through isn't finished until acidic workup (e.g. H₃O⁺, heat) restores the original carbonyl.
Quick Recall
What are the two key reactive sites the MCAT expects you to recognize?
In the worked example, what protects the ketone, and what removes the protecting group at the end?
What is the general priority rule for predicting which functional group reacts first?
List the 5 steps of the reaction-problem framework.