Organic Chemistry 3331-200, Spring 2005

 Outline of Lecture Topics

• Review of carbonyl compounds
  • Stability of carbonyl group
  • Relative reactivity of carbonyl groups and nucleophilic addition
• Reactions that form the carbonyl group
  • Ozonolysis of alkenes
  • Oxidation of alcohols
  • Friedel-Crafts acylation of aromatics
• Review of keto-enol tautomerism

• Nucleophilic addition of metal hydrides (carbonyl reduction)
  • Alcohols from aldehydes and ketones
  • Alcohols from esters
  • Amines from amides

• Nucleophilic addition of water and hydroxide
  • Hydrate formation from aldehydes and ketones
  • The Cannizzaro reaction
• Nucleophilic addition of alcohols
  • Formation and hydrolysis of acetals and ketals
  • Using acetals and ketals as protecting group

• Nucleophilic addition of ammonia, amines, and other nitrogen nucleophiles
  • Formation of imines, hydrazones, etc.
  • Synthesis of amines by reductive amination
  • Formation of enamines
• The chemistry of carboxylic acids and acid derivatives
  • Intro

• Acid derivatives continued
  • Ester hydrolysis and acid-catalyzed esterification
  • Synthesis of acid derivatives from acid chlorides
  • Hydrolysis of nitriles
  • Cyanohydrins

• Nucleophilic addition of carbon nucleophiles
  • The Grignard synthesis of alcohols
  • The Wittig reaction - synthesis of alkenes from aldehydes and ketones

• Carbonyl nucleophiles - enolate anions and enols
• Halogenation of ketones
  • Halogenation in base: The haloform reaction
  • Halogenation in acid: Mono-halogenation of ketones

• Halogenation of carboxylic acids: The HVZ reaction
• Quantitative formation of ester and ketone enolates using LDA
• Kinetic vs. thermodynamic ketone enolate formation
• Alkylation of enolates with alkyl halides

• Reactions where carbonyl compounds are both nucleophile and electrophile
  • The aldol reaction under base-promoted conditions, and in acid
  • Synthesis of alpha-beta unsaturated ketones using the aldol reaction

• Nucleophilic addition to unsaturated ketones
  • 1,2-addition with alkyllithium and Grignard reagents
  • 1,4-addition (conjugate addition) with dialkyl cuprates
• The Michael addition (conjugate addition of stabilized enolates)
• The Robinson annulation sequence

• The Claisen condensation and Dieckmann cyclization
• Zn-enolate addition to ketones (the Reformatsky reaction)

• The crossed Claisen condensation and review

• More review

• Alkylation of beta-ketoesters and beta-diesters
• Decarboxylation of beta-ketoesters and beta-diesters: The malonic ester synthesis of esters and acids, and the aceto-acetic ester synthesis of ketones

• Carbocation rearrangements by 1,2-hydrogen or 1,2-alkyl shifts
• The pinacol rearrangement
• An anionic rearrangement - the benzylic acid rearrangement
• Pericyclic reactions
  • The Diels-Alder reaction - review of a reaction with no cationic, anionic, or radical intermediate
  • Pericyclic rearrangements
  • The Cope rearrangement

• More Cope rearrangement
• Electrocyclic ring formation and ring opening
• The Beckmann rearrangement - synthesis of amides from ketones
• The Hofmann rearrangement - synthesis of amines from amides

• The Baeyer-Villiger Oxidation - synthesis of esters from ketones
• The Claisen rearrangement

• Review of C-C bond formations

• Intro to directed organic synthesis

• More intro to directed organic synthesis
• Synthesis "case studies" - Alcohol and ketone synthesis using enolate alkylation or the Grignard reaction
  • 2-butanone and 2-butanol from 3C alcohols
  • Reveiw of the acetoacetic ester synthesis of ketones

• Examples from exercise 15.2
• Dealing with multiple functional groups - protecting groups

• Protection of amines and carboxylic acids
• Real-world case studies in director organic synthesis
  • Ibuprofen and ketoprofen - using nitriles as acid equivalents
  • Synthesis of heterocycles - Benzodiazepines

• Syntheses that involve rearrangments
• Start review of Ch 13.5, 14, 15

• Introduction to polymers
• Polyethylene, graphite and diamond
• Linear and branched polymer

• Latex, elastomers, poly-butadiene, and cross-linking
• The thermodynamic basis of elasticity
• polystyrene/divinylbenzene
• Polymerization of epoxides and polyethyleneglycol (PEG)

• Polyvinylalcohol
• Polyesters
• We will cover polysaccharides as part of Chapter 17
• Polyamides - Nylon (we'll cover polypeptides in Chapter 18)
• Polyurethanes
• Epoxy resins and Bakelite

• Lipids and self-assembly

• Biosynthesis of terpenes
  • Alkyl phosphates as electrophiles
• Carbohydrates
  • Glyceraldehyde and dihydroxyacetone - aldoses and ketoses
  • Aldotetroses
  • Aldopentoses - cyclic hemiacetals, ribose furanose and pyranose forms, anomers

• Converting between Fischer projections of the open chain form of sugars, and Haworth projections (for furanoses) and perspective chairs (for pyranoses).
• Aldohexoses - glucose et al.

• Aldoketoses - fructose
• Carbohydrate dimers - sucrose
• Carbohydrate polymers - starch and glycogen
• Nitrogen-containing natural products
  • Review of synthesis of amines and amides
  • Nucleophilic addition to imines (Grignard synthesis with imine electrophiles)

• The Mannich condensation (aldol reaction with imine electrophiles)
• Amino Acids - intro

• Amino Acids - acid/base chemistry
• Polypeptide primary and secondary structure - alpha helix and beta sheet
• Polypeptide synthesis

• Intro to nucleic acids - DNA and RNA

• Highlights from Professor Walba's research: The invention of liquid crystal on silicon HDTV, and the discovery of chiral liquid crystals made from achiral molecules - This lecture is purely discressionary; the material will not be on the final.

• Introduction to cofactors
• Pyridoxamine phosphate - biological reductive amination

• Oxidative deamination catalyzed by pyrodoxal phosphate
• Thiamine and lipoic acid - decarboxylation of alpha keto acids
• Key steps in synthesis and "burning" of fatty acids
  • NADPH - Biological hydride reduction/alcohol oxidation
  • FADH2 - Biological "dissolving metal reduction"

• Intro to glycolysis
• FCQ

• The glycolytic pathway