⚗️ Synthesis
Retrosynthesis: work backwards from target using '=>' (retrosynthetic arrow)
Retrosynthetic Analysis
Start at the target molecule and work backwards. Identify key bond disconnections. Use '=>' retrosynthetic arrow. Each step asks: 'What two pieces could combine to make this?' Transform target into simpler precursors.
⚗️ Synthesis
Protect, React, Deprotect — the synthesis mantra
Protecting Groups Strategy
When a reagent would react with multiple functional groups, PROTECT the one you don't want to react. Common protections: alcohol → TMS ether or acetal. Amine → Boc or Cbz. Carbonyl → acetal. Then react. Then deprotect.
⚗️ Synthesis
Disconnection at C-C bonds formed by: Grignard, aldol, Wittig, Diels-Alder
Key C-C Bond Forming Reactions
Most synthesis problems hinge on C-C bond formation. Key reactions: Grignard (RMgX + carbonyl). Aldol condensation. Wittig (carbonyl → alkene). Diels-Alder (diene + dienophile → cyclohexene). Know these 4.
⚗️ Synthesis
Diels-Alder: diene must be s-cis conformation, electron-rich diene + electron-poor dienophile
Diels-Alder Reaction
Concerted [4+2] cycloaddition. Diene must adopt s-cis conformation. Best with electron-donating groups on diene, electron-withdrawing groups on dienophile. Stereospecific: syn addition, endo rule for major product.
⚗️ Synthesis
Oxidation state changes: reduction adds H or removes O, oxidation removes H or adds O
Oxidation State Tracking
Track oxidation states to plan redox steps. Reduction: add H2 (hydrogenation), add H⁻ (NaBH4/LiAlH4), or remove O. Oxidation: add O (KMnO4, OsO4) or remove H (PCC, Cr2O7²⁻). Balance oxidation states across synthesis.