Organic Synthesis and Mechanisms

70 lessons, pages 3311–3380.

  1. Organic Synthesis: The Big Picture — Why chemists build molecules and how mechanisms guide the plan
  2. Curly Arrows Revisited: Tracking Electron Flow — Rules for drawing arrows from electron-rich to electron-poor centres
  3. Nucleophiles, Electrophiles and Orbital Control — HOMO–LUMO interactions behind polar reactions
  4. SN2 in Depth: Backside Attack and Inversion — Concerted substitution, transition state geometry and Walden inversion
  5. Factors Controlling SN2 Rates — Substrate hindrance, nucleophile strength, leaving group and solvent
  6. E2 in Depth: Antiperiplanar Geometry — Concerted elimination and the stereoelectronic requirement
  7. Substitution versus Elimination: Choosing the Pathway — How base strength, bulk, substrate and temperature decide the outcome
  8. The Carbonyl Group: Structure and Polarity — Bonding, dipole and the π* orbital of C=O
  9. Carbonyl Reactivity: Aldehydes, Ketones and Acid Derivatives — Electronic and steric effects on electrophilicity
  10. Nucleophilic Addition to Carbonyls: The General Mechanism — Attack at the Bürgi–Dunitz angle and the tetrahedral intermediate
  11. Hydride Reductions of Carbonyl Compounds — Sodium borohydride and lithium aluminium hydride compared
  12. Organometallic Addition: Grignard and Organolithium Reagents — Carbon nucleophiles that build alcohols and new C–C bonds
  13. Cyanohydrins and Carbon Chain Extension — Cyanide addition and the synthetic uses of the nitrile product
  14. Hydrates, Hemiacetals and Acetals — Reversible addition of water and alcohols under acid catalysis
  15. Acetals as Protecting Groups — Masking a carbonyl while another group reacts
  16. Imines and Enamines from Carbonyl Compounds — Condensation with primary and secondary amines
  17. The Wittig Reaction — Phosphorus ylides turning C=O into C=C
  18. Stereochemistry of Carbonyl Addition — Re and Si faces and new stereocentres
  19. Nucleophilic Acyl Substitution: Addition–Elimination — The tetrahedral intermediate and leaving group ability
  20. Acyl Chlorides and Anhydrides as Acylating Agents — The most reactive acid derivatives and their uses
  21. Esters: Formation, Hydrolysis and Transesterification — Acid and base catalysed mechanisms and saponification
  22. Amides and Nitriles: The Least Reactive Derivatives — Resonance stabilisation and hydrolysis under forcing conditions
  23. Reducing and Alkylating Acid Derivatives — Hydride and organometallic reagents with esters and amides
  24. Oxidation Levels and Carbonyl Interconversions — Mapping alcohols, aldehydes, acids and derivatives by oxidation level
  25. Carbonyl Chemistry: Checkpoint Review — Consolidating addition and acyl substitution chemistry
  26. Keto–Enol Tautomerism — Acid and base catalysed interconversion and equilibrium position
  27. Acidity of α-Hydrogens — Resonance-stabilised enolates and pKa comparisons
  28. Forming Enolates: Choosing the Base — Alkoxides versus LDA and complete versus partial deprotonation
  29. Kinetic versus Thermodynamic Enolates — Regioselective enolate formation from unsymmetrical ketones
  30. α-Halogenation of Carbonyl Compounds — Acid versus base conditions and the haloform reaction
  31. Alkylation of Enolates — SN2 reactions of enolates with alkyl halides
  32. Enamines as Enolate Equivalents — Stork enamine alkylation and acylation
  33. The Aldol Addition — Enolate attack on a carbonyl to give β-hydroxy carbonyls
  34. Aldol Condensation and Dehydration — Forming conjugated enones by E1cB elimination
  35. Crossed and Directed Aldol Reactions — Controlling which partner is enolate and which is electrophile
  36. The Claisen Condensation — Ester enolates giving β-keto esters
  37. Dieckmann Cyclisation and Crossed Claisen Reactions — Intramolecular and mixed ester condensations
  38. 1,3-Dicarbonyl Compounds and Stabilised Enolates — Doubly activated methylene groups and their low pKa
  39. The Malonic Ester Synthesis — Alkylation then decarboxylation to substituted acetic acids
  40. The Acetoacetic Ester Synthesis — Building substituted methyl ketones
  41. Conjugate Addition: The Michael Reaction — 1,4-addition to α,β-unsaturated carbonyls
  42. The Robinson Annulation — Michael addition followed by intramolecular aldol to build rings
  43. Enolate Chemistry in Living Systems — Aldolases, Claisen-type enzymes and fatty acid biosynthesis
  44. Enolate Chemistry: Checkpoint Review — Consolidating enol, enolate and condensation reactions
  45. Introduction to Pericyclic Reactions — Concerted cyclic transition states and the main reaction classes
  46. Frontier Molecular Orbitals of Conjugated π Systems — HOMO and LUMO symmetry in ethene, butadiene and hexatriene
  47. The Diels–Alder Reaction: Mechanism — A [4+2] cycloaddition forming six-membered rings
  48. Diels–Alder Stereochemistry and the Endo Rule — Stereospecificity and secondary orbital interactions
  49. Diene Conformation and Diels–Alder Regiochemistry — The s-cis requirement and ortho/para orientation
  50. Electrocyclic Reactions — Ring closure and ring opening of conjugated polyenes
  51. Conrotatory and Disrotatory Motion — Thermal and photochemical stereochemical outcomes
  52. Sigmatropic Rearrangements: Cope and Claisen — [3,3] shifts through chair-like transition states
  53. Photochemical [2+2] Cycloadditions — Why light allows four-membered ring formation
  54. The Woodward–Hoffmann Rules: An Introduction — Counting electrons to predict allowed pericyclic reactions
  55. Retrosynthetic Analysis: Working Backwards — The target molecule and the disconnection approach
  56. Disconnections and Synthons — Idealised fragments and their real reagent equivalents
  57. Functional Group Interconversion in Planning — Changing one group into another to enable a disconnection
  58. Protecting Group Strategy — Choosing, installing and removing protecting groups
  59. Chemoselectivity and Regioselectivity — Reacting one group or one site in the presence of others
  60. Stereoselective Synthesis — Diastereoselectivity, enantioselectivity and chiral catalysts
  61. The Carbon–Carbon Bond Forming Toolkit — Comparing organometallic, enolate, Wittig and Diels–Alder methods
  62. Multi-Step Synthesis: Yield and Efficiency — Linear versus convergent routes and overall yield
  63. Green Chemistry in Synthesis — Atom economy, catalysis and reducing waste
  64. Monitoring Reactions and Confirming Products — Using TLC, IR and NMR evidence in synthesis
  65. Case Study: Planning the Synthesis of Ibuprofen — Comparing a classic route with a greener industrial route
  66. Case Study: Pericyclic Steps in Natural Product Synthesis — How Diels–Alder reactions build complex ring systems
  67. Solving Mechanism Problems Systematically — Identifying nucleophile, electrophile and the key bond changes
  68. Common Errors in Mechanism Drawing — Arrow direction, charges, valency and impossible intermediates
  69. Exam Skills: Synthesis Roadmaps — Connecting reactions into multi-step routes under exam conditions
  70. Organic Synthesis and Mechanisms: Unit Review — Bringing together carbonyl, enolate and pericyclic chemistry