1. Why study Organic Synthesis?
Organic Chemistry of Fine Chemicals
Spring 2006
Why study Organic Synthesis?
Heart of Chemistry
Broad applications
Petrochemicals
Pharmaceuticals
Agrochemicals
(Bio)Polymers
Dyes & Pigments
Cosmetics
Food (Additives)
Household products
Electrochemicals
Display materials
Semiconductors
Organic electronics
and so on…..
“Chemists make new things and we study reactions. That’s the core of this profession” - D.G. Nocera (MIT) in C&EN (Jan. 1998)
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2. Petrochemicals
phenol
acetone
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3. Pharmaceuticals & Medicinal Chemistry
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4. Agrochemicals
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5. Polymers & Biopolymers
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6. Biology & Biochemistry
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7. Electrochemicals
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8. Display Materials
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9. Components of Organic Synthesis
Synthetic work
experimental procedures
TARGET
Retrosynthetic analysis
Synthetic design
‘disconnection approach’
1. C-C bond formation
2. functional group interconversion (FGI)
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10. Disconnection Approach: An Example
alkylation
synthons
LiN(iPr)2 
acetal
H+ (-H2O)
synthetic
equivalents
OsO4
oxidation
multistriatin: a pheromone of the elm bark beetle ?
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11. A Stereorandom Synthesis of Multistriatin
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12. A Stereoselective Synthesis of Multistriatin
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13. Design and Synthesis Retrosynthetic Analysis Synthesis
1. recognise the functional groups in the target molecule
2. disconnect by known methods and reliable reactions
3. repeat 1 and 2 until the readily available starting materials are obtained
4. design as many alternative retrosynthetic routes as possible
Synthesis
1. write down the synthetic schemes containing the detailed reaction conditions according to the analyses
2. compare the pros and cons between the syntheses designed; the number of steps, availability of reagents/starting materials, selectivity (chemo-/regio-/stereo-), economy, process, etc
3. modify the selected synthetic plan whenever unexpected problems are encountered
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14. What to Know for Organic Synthesis
molecular structure
reaction mechanisms
stereochemistry
dependable reactions
availability of compounds
selectivity
analytical methods
lab technique
process
creativity
economy
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15. 공 부 하 는 방 법
“그저 익숙하도록 읽는 것뿐이다. 글을 읽는 사람이, 비록 글의 뜻은 알았으나, 만약 익숙하지 못하면 읽자마자 곧 잊어버리게 되어, 마음에 간직할 수 없을 것은 틀림없다.
이미 읽고 난 뒤에, 또 거기에 자세하고 익숙해질 공부를 더한 뒤라야 비로소 마음에 간직할 수 있으며, 또 흐뭇한 맛도 있을 것이다.” - 퇴계 이황 (금장태 著)
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16. Chapter 2 Functional Group Transformations
Organic Chemistry of Fine Chemicals
Spring 2006
Chapter 2 Functional Group Transformations
selectivity/specificity: chemo-, regio- & stereo-
functionalization of alkanes: unreactive
radical reaction: selectivity;  5 bottom
functionalization of alkenes: addition & substitution
addition to double bonds:  6 Scheme 2.1
‘(anti)Markovnikov’/oxymercuration/hydroboration/HBr:  7 top
stereoselectivity:  7 bottom
allylic substitution: radical;  8 top & 188~189 (oxidation)
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17. Chemoselectivity regioselectivity & stereoselectivity H2, Pt NaBH4
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18. Regioselectivity more electropositive metals: Mo, W 1. BH3•THF H3O+
2. H2O2, NaOH
Hg2+, H2O/NaBH4
more electropositive metals: Mo, W
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19. Diastereoselectivity (I)
major
minor
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20. Diastereoselectivity (II)
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21. Enantioselectivity
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22. Functionalization of Alkynes
Organic Chemistry of Fine Chemicals
Spring 2006
Functionalization of Alkynes
addition / substitution reactions:  9 Scheme 2.2
reduction to alkenes:  165 bottom – 166
C-C bond formation:  51 – 52 top
electrophilic addition: largely anti addition
a mixture of products: syn addition & participation of the reaction solvent,  8 bottom – 9 top
ketones with oxymercuration:  9 middle
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23. Functionalization of Aromatic Hydrocarbons
Organic Chemistry of Fine Chemicals
Spring 2006
Functionalization of Aromatic Hydrocarbons
electrophilic substitution: the ring;  10 Scheme 2.3
substituted benzenes: depending on the substituents
the rate & the orientation:  11 Table 2.1 &  12
lower selectivity with a radical substitution:  13 top
nucleophilic substitution: p-chloronitrobenzene
Chichibabin reaction ( 14 & 44) & benzyne intermediate
benzylic oxidation: the side chain;  189~192
autoxidation of cumene: acetone & phenol;  11 top
chlorination/bromination: radical mechanism;  11 top
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24. Functionalization of Aromatic Heterocycles
Organic Chemistry of Fine Chemicals
Spring 2006
Functionalization of Aromatic Heterocycles
pyridine: weak base & e--poor ring,  14 Scheme 2.4
electrophilic substitution: difficult but higher e--density at C-3
nucleophilic substitution at C-2: ‘Chichibabin’;  14 Scheme 2.5
substitution of pyridine-N-oxide at C-4:  15 Scheme 2.6
pyrrole, furan, thiophene: e--rich;  16 Scheme 2.7
substitution at C-2 / C-5: resonance-stabilized
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25. Interconversion of Functional Groups
Organic Chemistry of Fine Chemicals
Spring 2006
Interconversion of Functional Groups
alcohols & phenols: less basic;  17 Scheme 2.8
amines: basic & nucleophilic;  20 Scheme 2.9
amines as electrophiles: pyridinium ions;  18 bot & 19 top
halides: good leaving groups;  21 Scheme 2.10
aryl nitro compounds:  22 Scheme 2.11
aldehydes & ketones: addition, substitution, enolates
carboxylic acids:  23 Scheme 2.12
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