CY6019 : Modern Synthetic Methodology in Organic Chemistry (Department Elective-I)

Course Objectives: To learn various organic reactions and reagents used in them as tools applied in the art of organic synthesis. To learn retrosynthetic approach towards organic synthesis.

Learning Outcomes: At the end of the course, the learners should be able to:

Use various reagents and organic reactions in a logical manner in organic synthesis.

Use retrosynthetic method for the logical dissection of complex organic molecules and devise synthetic methods

Course Contents:

Oxidation: Metal based and non-metal based oxidations of alcohols (chromium, manganese, silver, ruthenium, DMSO, and hypervalent iodine). (b) Peracids oxidation of alkenes and carbonyls. (c) Alkenes to diols (manganese, osmium based), alkenes to carbonyls with bond cleavage (manganese, ruthenium, and lead based, ozonolysis), and alkenes to alcohols/carbonyls without bond cleavage (hydroboration-oxidation, Wacker oxidation, and selenium based allylic oxidation). (d) Asymmetric epoxidations (Sharpless, Jacobsen, and Shi epoxidations) and Sharpless asymmetric dihydroxylation.

Reduction: (a) Catalytic homogeneous and heterogeneous hydrogenation, Wilkinson catalyst. (b) Metal based reductions using Li/Na in liquid ammonia, sodium, magnesium, zinc, titanium, and samarium. (c) Hydride transfer reagents: NaBH4, L-selectride, K-selectride, Luche reduction, LiAlH4, DIBAL-H, Red-Al, Trialkylsilanes, and Trialkylstannane. (d) Enantioselective reductions (Chiral Boranes, Corey-Bakshi-Shibata) and Noyori asymmetric hydrogenation.

Modern Synthetic Methods: (a) Baylis-Hillman reaction, Henry reaction, Kulinkovich reaction, Ritter reaction, Sakurai reaction, Brook rearrangement, Tebbe olefination. (b) Metal mediated C-C and C-X coupling reactions: Heck, Stille, Suzuki, Negishi and Sonogashira, Nozaki-Hiyama, Buchwald-Hartwig, Ullmann coupling reactions, directed ortho metalation. (c) Stereoselective synthesis of tri- and tetra-substituted olefins, Synthetic applications of Claisen rearrangement, ene reaction (metallo-ene, Conia ene).

Construction of Ring Systems: (a) Different approaches towards the synthesis of three, four, five, and six-membered rings. (b) Pauson-Khand reaction, Bergman cyclization; Nazarov cyclization, cation-olefin cyclization and radical-olefin cyclization, inter-conversion of ring systems (contraction and expansion). (c) Construction of macrocyclic rings and ring closing metathesis.

Retrosynthetic Analysis: Basic principles and terminology of retrosynthesis, synthesis of aromatic compounds, one group and two group C-X disconnections, one group C-C and two group C-C disconnections, amine and alkene synthesis, important strategies of retrosynthesis, functional group transposition, important functional group interconversions Protecting groups: Protection and deprotection of hydroxy, carboxyl, carbonyl, carboxy amino groups and carbon-carbon multiple bonds; chemo- and regioselective protection and deprotection; illustration of protection and deprotection in synthesis.

Text Books:

1. Carruthers, Modern Methods of Organic Synthesis, Cambridge University Press, 1996.
2. Kuerti and B. Czako, Strategic Applications of named Reactions in Organic Synthesis, Elsevier Academic Press, 2005.
3. Clayden, N. Greeves, S. Warren and P. Wothers, Organic Chemistry, Oxford University Press, 2001.
4. A. Cary and R. I. Sundberg, Advanced Organic Chemistry, Part A and B, 5th Edition, Springer, 2009.
5. B. Smith, Organic Synthesis, 2nd Edition, 2005
6. Warren, Organic Synthesis, The disconnection Approach, John Wiley & Sons, 2004.
7. Tsuji, Palladium Reagents and Catalysts, New Perspectives for the 21st Century, John Wiley & Sons, 2003.
8. Ojima, Catalytic Asymmetric Synthesis, 2nd edition, Wiley−VCH, New York, 2000.
9. Noyori, Asymmetric Catalysis in Organic Synthesis, John Wiley & Sons, 1994.