Organic Synthesis I 1. Main text : Adv. Org. Syn. (4 th Ed.) Part B, Carey & Sundberg 2. Aim : acquiring various reactions and synthetic strategies to design synthetic routes for target molecules 3. Other texts & ref. : a)Designing Organic Synthesis – S. Warren b)Modern Organic Synthesis – D. L. Boger c)Advanced Organic Chemistry – J. March d)Modern Methods of Organic Synthesis (4 th Ed.) – W. Carruthers e)Organic Synthesis (2 nd Ed.) – J. Furhop, G. Penzlin f)Classics in Total Synthesis I, II – K.C. Nicolaou g)The Logic of Chemical Synthesis – E. J. Corey

What will be covered in Org. Syn. I Chapter 1 : Alkylation – carbanion Chapter 2 : Reaction of Carbon Nu: w/ carbonyl Chapter 3 : Functional group interconversion Chapter 5 : Reduction of Carbonyl etc. Chapter 7 : Organometallic – main group Chapter 12 : Oxidation Chapter 13 : Planning and Execution ** Named Reactions** ** Reaction Mechanism** Homework : Selected problems from each chapter

Reaction Mechanism (or reasonably drawn detailed reaction pathway) is important -- Examples -- i) esterification ii) acetals iii) aldol J. Am. Chem. Soc., 1914, 36, 530 iv) Cannizzaro rxn.

esterification acetals

aldol Cannizzaro rxn.

Classification of Organic Synthesis 1.Linear Synthesis : tedious, inefficient but could be simple ex.) DNA, Peptide Synthesizer 2. Convergent Synthesis -- economic, time saving 3. Divergent Synthesis -- SAR, Combichem. 4. Biosynthesis driven Synthesis -- biomimetic synthesis 5. Symmetry considered synthesis -- simplification 6. Systematic Synthetic analysis and design

Objective of Organic Synthesis 1. Target : to be conquered ---- speed, elegance 2. Structural Information ---- unambiguous 3. S. A. R. : for design ---- creativity 4. Usefulness ---- economy

Chronology of Organic Synthesis - 19C. Europe : Industry driven – Dyestuff, Aspirin - America : Weak Industry – more academic 1. Cope : PennState, MIT 2. Woodward : creativity 3. Stork : 3-dimensional world 4. Corey : Logic 5. Kish : managing

** Perception of a target ** 1. Static -- shape -- Design 2. Dynamic -- relationship -- Control ** Things to Consider ** 1. Connectivity -- symmetry, complexity 2. Stereochemical relationship 3. Functionality -- substructures 4. Reactivity : Stability -- air, heat, light, acid, base …… 5. Compatibility 6. Kinetic vs. Thermodynamic relationship 7. Products -- volatile, syrup, solubility in water, hazard, smell….. 8. Characterization of the target molecules

Synthetic Chemistry in the 21 st Century Ideal Synthesis safe simple 100% yield Available material One step Environmentally acceptable Resource efficient

Beginning of Organic Chemistry Woehler (1828) Beginning of Organic Synthesis Kolbe (1845)

Stork (2001)

 Terpinol

Provide a reasonable arrow-pushing mechanism for the following reaction Answer

Provide a reasonable arrow-pushing mechanism for the following reaction