COMPLEMENTS OF ORGANIC CHEMISTRY
Students should possess a deep knowledge of organic chemistry, as learned during the courses of Organic Chemistry 1 and Organic Chemistry 2.
The verification of students’ preparation is carried out through a written examination. Exercises typology may include: 1) a guided synthesis; 2) planning the synthesis of a target molecule starting from a given precursor; 3) reactivity of a molecule in presence of a set of reagents.
At the end of the course, students should demonstrate to be able to
a) depict in detail the mechanism of the most important reactions of oxidation, reduction and interconversion among the main functional groups;
b) plan a multi-step synthesis of a given target starting from given precursors, with special attention to chemo- and stereoselectivity.
Definition and examples of selectivity (regio-, chemo-, stereo-). Stereospecificity.
Oxidation reactions. DMSO-mediated oxidations (methods of Albright, Pfitzner Moffatt, Barton, Parikh Doering, Swern). Corey Kim method. Dess Martin periodinane. Ley Griffith Method (TPAP). Salts of N-oxoammonium (TEMPO). Oppenauer reaction. Oxidation by hypochlorite. Oxidation by MnO2, DDQ, pyridinium chlorochromate (PCC), pyridinium dichromate (PDC), Sarrett, Pinnick. Oxidations by KMnO4, Ag oxide, bromine.
Baeyer Villiger reaction. Corey Ganem method. Alpha-hydroxylation of carbonyl groups: Vedejs, Rubottom, Davis, oxidation of enolates. Malaprade oxidation. Lead(IV) acetate. Ozone. Lemieux Johnson, Lemieux Rudloff, ruthenium tetroxide and derivatives. Fetizon, oxidations with SeO2. Oxidations with 1O2. Epoxidation of alcohols. Nucleophilic epoxidation. Enantioselective epoxidation (Jacobsen, Shi and Sharpless). Dihydroxylation of alkenes (osmylation, Upjohn process, KMnO4, Sharpless). Methods of Prévost and Woodward. Oxidation to alpha-diketones (Riley). Oxidation of nitrogen compounds. Oxidation of sulfur compounds.
Reduction reactions. Classification of reducing agents: electrophilic and nucleophilic hydrides. LiAlH4, Redal® Hydroalumination. Reduction of epoxides (Fürst Plattner rule). DiBAH, LiAl(OtBu)3H, diborane. NaBH4, LiBH4, Super-Hydride®, K- and L-selectride®, NaBH3CN. Chemoselectivity in reductions with hydrides. Weinreb amides. Ionic reduction (Kursanov). Reduction of aldehydes/ketones to methyl/methylene: Wolff Kishner, Clemmensen, Mozingo, through tosylhydrazone. Reduction of alcohols to alkanes from tosylate or alkyl halides. Barton McCombie method. Catalytic hydrogenation (general). Reduction of (E/Z-)alkenes or alkynes (Diimide. Formic acid. Hydride transfer (Hantzsch ester). Reductions via SET (Birch, McMurry). Use of Sm(II) iodide and Bu3SnH.
Synthesis and interconversion of the main functional groups. Mitsunobu reaction. Synthesis of alcohols, phenols, (aliphatic and aromatic) aldehydes and (aliphatic and aromatic) ketones. Synthesis of (aliphatic and aromatic) carboxylic acids. Synthesis of esters (Tischenko reaction). Synthesis of amides. Synthesis of (aliphatic and aromatic, Buchwald Hartwig) amines. Synthesis of nitriles. Synthesis of alkyl (Appel) and aryl halides. Metal-organic reagents (lithium-, magnesium-, copper). C-C coupling catalyzed by Pd (Heck, Suzuki, Stille, Sonogashira). Synthesis of simple targets using enolates.
The course exclusively consists of 48 hours of front lectures, during which students are assigned exercises concerning the lessons topics.
The Professor is available to meet the students in his office (Via Valleggio 9, 4th flour) upon appointment by e-mail.