MAKING COMPLEX MOLECULES

1. MAKING COMPLEX MOLECULES Fischer achieved the first synthesis of the first truly complicated organic molecules, the sugar molecule D-glucose in 1890. Hermann Emil Fischer Germany (1852-1919) D-Glucsoe The Nobel Prize in Chemistry 1902 Fischer’s work on the total synthesis of D-glucose is regarded as the catalyst for the development of synthetic organic chemistry in the 20th century.

2. Sir Robert Robinson United Kingdom (1886-1975) Willstatter’s synthesis of tropine The Nobel Prize in Chemistry 1947 Robinson’s synthesis of tropinone in 1917 The Robinson’s synthesis of tropinone was hailed as revolutionary. This was to look at the target molecule and try to imagine how the molecule could be constructed from simpler chemical units.

3. Sir Christopher Kelk Ingold (1893-1970) Mechanism?

4. Sir Derek H. R. Barton (1918-1998) Conformational Analysis The Nobel Prize in Chemistry 1969 "for their contributions to the development of the concept of conformation and its application in chemistry"

5. 1H NMR spectrum of cyclohexane-d11 at different temperature

6. Robert Burns Woodward

7. Some of the Complex Molecules Made by Woodward “There is excitement, adventure, and challenge, and there can be great art in organic synthesis.” - Woodward Quinine (1944) anti-malarial drug Vitamin B12 (1973) Strychnine (1954) pesticide

8. Some prostaglandins affect human blood pressure at concentrations as low as 0.1 microgram per kilogram of body weight. Substances that inhibit prostaglandin synthesis may be useful in controlling pain, asthma attacks, and anaphylactic shock and in reducing the clotting ability of blood. Corey, Elias James 1928–, b. Methuen, Mass., grad. Massachusetts Institute of Technology (B.S. 1948, Ph.D. 1951). In 1990, he was awarded the Nobel Prize in Chemistry. “The organic chemist is more than a logician and strategist; he is an explorer strongly influenced to speculate, to imagine, and even to create.” - Corey Prostaglandins

9. Retrosynthetic Analysis by Corey Retrosynthetic analysis (orretrosynthesis) : the process of mentally breaking down a molecule into starting materials Retrosynthetic arrow: an open-ended arrow, , used to indicate the reverse of a synthetic reaction Synthon: idealized fragments resulting from a disconnection. Synthons need to be replaced by reagents in a suggested synthesis Retrosynthetic analysis for violet oil component Synthesis of violet oil component

10. Organic Synthesis: • Carbon-Carbon Bond Formation • Functional Group Interconversion Enantioselectivity

11. Some Physical Properties of the Stereoisomers of Tartaric Acid

12. Louis Pasteur was born on December 27, 1822 in Dole, in the region of Jura, France. Louis Pasteur Chemist Resolution of enantiomers in 1848 1822-1895 Twenty years later, J. H. van’t Hoff and J.-A. Le Bel independently explained the origins of enantiomers based on the tetrahedral nature of carbon bonding. “Chance favors only prepared mind.” -Louis Pasteur

13. Resolution diastereomeric salts  seperation by selective crystallization or some other means Once separated, acidification of the two diastereomeric salts with strong acid gives pure enantiomers and recover the chiral amine.

14. Asymmetric Synthesis Synthesis of One Enantiomer using a Chiral Auxiliary [ ] Chiral Auxiliary :

15. Asymmetric Synthesis Synthesis of an Enantiomer using a Chiral Reagent Hebert C. Brown (1912- ) The Nobel Prize in Chemistry 1979 "for their development of the use of boron- and phosphorus-containing compounds, respectively, into important reagents in organic synthesis"

16. Asymmetric Synthesis Synthesis of an Enantiomer using a Chiral Catalyst 92% yield, 97%ee

17. Asymmetric Synthesis Synthesis of an Enantiomer using a Chiral Catalyst

18. The anticancer drug, Taxol Synthesis: K. C. Nicolaou at The Scripps Research Institute Robert Holton at Florida State University

19. Organometallic Chemistry Organometallic Compounds Carbon Species carbocation stable (neutral) carbene carbanion radical unstable species Acid-Base Chemistry relatively stable complex

20. 1. Stabilize unstable organic compounds - strained, unstable - does not exist at normal temperatures and pressures - reacts with itself to form larger ring - stable - well-behaved and easily-manipulated - readily seperated - a convenient source of cyclobutadiene

21. 2. Change characters of organic compounds - surrounded by a cloud of negative electrons - prefer to interact withpositively-charged molecules - reacts with itself to form larger ring - Cr(CO)3 sucks away electrons from benzene - prefer to interact with negatively-chargedmolecules

22. 3. organometallic complexes: useful templates (as reagents) Pauson-Khand Reaction: 1970s - useful method for the synthesis of cyclopentenone

23. Application to the synthesis of complex molecules taylorione: synthesis by Williams Kerr in 1990s

24. 4. Catalyze Reactions: efficiency in early 1990s, Bob Grubbs at California Institute of Technology Olefin metathesis - for some time had been used for synthesis of polymers but had been overlooked by organic chemists - alkenes are one of the most important building block - abundant in nature's chemicals: vitamin A, quinine, chlorophyll - manmade organic chemicals: pharmaceuticals, perfumes, flavoring

25. Olefin Metathesis catalysts for olefin metathesis: many catalysts based on organometallic reagents "Ru", "Mo", "W" Grubbs's catalyst

26. Olefin Metathesis mechanism

28. Ring-Closing Olefin Metathesis