Stereoselective Organic Synthesis

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Lecture - This course is designed to provide graduate level of knowledge on diastereoselective and enantioselective organic synthesis. An emphasis will be placed on understanding of influence of mechanism and transition state structure on a stereoselective outcome of the reaction. The most important concepts will be illustrated by the total syntheses of complex natural compounds.

Laboratory - Organic chemistry, multi-stage syntheses under anhydrous conditions

Lecture - The lecture is aimed at presentation of basic concepts and modern methods of asymmetric organic synthesis.

The first part of the lecture will introduce fundamental concepts and definitions: chemoselectivity, regioselectivity, stereoselectivity, enantio- and diastereoselectivity. Next, methods for determination of enantiomeric and diastereoisomeric excess will be critically discussed. The next lectures will focus on additions of organometallic reagents to carbonyl group including thorough discussion of Cram and Felkin-Ankh models, with emphasis on broad applicability of Felkin-Ankh model in asymmetric synthesis. Following parts of the lecture will introduce methods for synthesis of chiral molecules with new stereogenic centers based on EPC synthesis, chiral auxiliary and chiral catalyst. Each concept will be thoroughly illustrated with chemical literature examples of important organic reactions:

- basics of homo- and hetero-Diels-Alder reaction as an excellent illustration for the diastereo- and enantioselective synthesis concepts,

- organometallic additions to carbonyl group, including Grignard reagents, organolithium compounds, dialkylzinc compounds including dialkylzinc mediated enantioselective alkynylation, alkenylation and arylation reactions,

- asymmetric allylic substitution reaction catalyzed by palladium, molybdenum and iridium complexes.

- Basic concepts of organocatalysis

Laboratory - Depending on the level of the laboratory skills, students are provided with the structure and/or name of the target compound and are obliged to find experimental procedures in the available chemical literature or procedures are provided by a teacher. Use of the computerized chemical databases as Reaxys and SciFinder is strongly encouraged. The short introduction to these databases will be provided by the teacher, if necessary. Proposed syntheses have at least three stages and allows students to learn about relationship between chemical yield of the single stage and final yield of the synthesis. Students improve their skills for work under anhydrous conditions, diminished pressure and separation of compound by column chromatography. Modern spectroscopy methods are used for the elucidation of the structure of synthesized compounds. The selection of the target compound is based on the actual research conducted at the Faculty of Chemistry.

Basics:

1. A. Vogel Vogel's textbook of practical organic chemistry

2. www.reaxys.com

References to appropriate articles in chemical journals will be given during the course

Lecture - After completing the lecture, a student:

a) should be able to choose best method for determination of enantioselectivity and diastereoselectivity

b) should be able to build a stereochemical model for simple enantio- and diastereoselective reactions

c) have a basic knowledge about most important methods for the stereogenic center creation.

Laboratory - Student should achieve ability to use special synthetic methods and good knowledge of using modern chemical databases and chemistry journals for planning organic syntheses.

Will have the proper skills for performing the organic synthesis under anhydrous conditions. Will be able to analyze reaction using TLC and isolate products by column chromatography including "flash" chromatography.

Lecture - Stationary final examination with open-ended questions.

Laboratory - Grading on the basis of the work in the laboratory (quality of the work, NOT the chemical yield of the reaction), description of the performed synthesis and the final test.