4 credits – 60 theoretical hours
OBJECTIVES:
Allow the student to gain knowledge and understanding of synthetic mechanisms and methods applied to organic chemistry
SUMMARY:
1. Carbon-carbon single bond formation processes
2. Carbon-carbon double bond formation processes
3. Cycloaddition Reactions.
4. Reduction
5. Oxidation
6. Protection Group
7. Retrosynthetic Analysis
PROGRAM CONTENT:
1. Carbon-Carbon Single Bond Formation Processes
Alkylation of Carbon Nucleophiles: Enolates and Enamines.
Formation and importance of the enolate ion; alkylation of aldehydes, ketones, esters, amides and nitriles;
alkylation of 1,3-dicarbonyl compounds.
Enamines and Imines: preparation, enamines as Michael’s reagent. Carboxylation of carbocations.
Condensation reactions: Aldol Condensation; Robinson annulation, Claisen-Schmidt,
Knoevenagel, Mannich and Reformatsky.
Synthetic applications of organometallics: Organolithium, Organocuprates and Organomagnesiums-
Grignard reagent. Other processes.
2. Carbon-Carbon Double Bond Formation Processes
Beta-elimination reactions. Pyrolytic eliminations. Oxidative decarboxylation of acids
carboxylics; decarboxylation of beta-lactones. Wittig and related reactions. Synthesis of
tri- and tetra-substituted alkenes. Fragmentation reactions. Rearrangements: Claisen, Sulfoxides. Others
processes.
3. Cycloaddition Reactions
Diels-Alder reaction: general process, diene and dienophile.
Intramolecular Diels-Alder and retro-Diels-Alder reactions. Stereochemistry, regiochemistry and Diels-Alder
Asymmetrical. 1,3-dipolar reactions.
4. Reduction
Catalytic hydrogenation: catalysts; reduction selectivity; reduction of functional groups;
stereochemistry and mechanism; homogeneous hydrogenation, hydrogenolysis. Reduction by metals in
solution: metals in an acidic medium; reduction of carbonyl substances, metals in alcoholic media;
metal in liquid ammonia. (Birch reduction). Reduction with hydride transfer reagents:
lithium aluminum hydride, sodium borohydride; aluminum alkoxides, diisobutyl hydrides
aluminum; sodium cyanoborohydride and trialkylborohydride. Reduction with boranes. Other methods:
Wolff-Kishner, desulfurization of thioketals, reduction with titanium.
5. Oxidation
Oxidation of hydrocarbons. Alcohol oxidation: with chromium and manganese compounds. Oxidation
of carbon-carbon double bonds: diols, epoxides with peracids and perester, epoxidation of
Sharpless, ozonolysis. Ketone oxidation: formation of α,β-unsaturated ketones, oxidation of
Bayer-Villiger. Oxidations with nickel peroxides. Oxidations with ruthenium tetroxide. Oxidation
with selenium dioxide. Oxidation of amines; oxidation of allylic carbon-hydrogen bonds.
6. Protection Group
The use of protecting groups in organic synthesis. Alcohol protection group. Group of
protection for phenol. Protection group for carbonyl substances. Protection group for
amines and amides. Reagents used for deprotection.
7. Retrosynthetic Analysis
Simple disconnection of connections. Synthetic equivalents. Concept of “synthons”. Interconversion
Functional Group (FGI). Strategy and planning of a synthetic route. Practical examples.
BIBLIOGRAPHY:
1. J. March, “Advance Organic Chemistry”, 3a. ed., Wiley, New York (1992).
2. F. A. Carey and R. J. Sundberg, “Advance Organic Chemistry,” Vol. 1. and 2, 2a. Ed., Plenum Press,
New York, (1993).
3. W. Carruthers, “Some Modern Methods of Organic Synthesis” 3a. Ed., Cambridge Press, London
(1987).
4. B. Mundy, “Concepts of Organic Synthesis”, Marcel Dekker, New York (1979).
5. H. O. House, “Modern Synthetic Reactions” Benjamin, Menlo Park, Calif. (1972).
6. J.C. Stowell, “Carbocations in Synthesis,” Wiley, New York (1979)
7. S. Warren, “Organic Synthesis: The Disconnections Approach,” Wiley, New York (1983).
8. M. B. Smith. “Organic Synthesis”, McGraw Hill, New York (2002).
9. S. Warren, “Workbook for Organic Synthesis: The Disconnections Approach,” Wiley, New York
(1985).
10. Willis and M. Wills. “Organic Synthesis”. Oxford Chemistry Primers. Oxford. New York. 1995.
11. Milõs Hudlicky, “Reductions in Organic Chemistry”, 2nd. ed, ACS Monograph 188, Washington,
(1996).
12. M. Hudlicky, “Oxidation in Organic Chemistry”, ACS Monograph 186, Washington, (1996).
