Simmons College

Department of Chemistry

Chemistry 343: Advanced Organic Chemistry: Asymmetric Synthesis

Spring 1998

Professor Nancy Lee

Class Time: M 3-4:30 & Th 10-11:30

Texts and Required Materials:

Carey & Sundberg, Advanced Organic Chemistry, 3rd Ed., Part B

R. J. Fessenden & J. S. Fessenden, Organic Chemistry, 4th or 5th Ed., (Brooks/Cole).

Solutions manual for Fessenden & Fessenden, 4th or 5th Ed., (Brooks/Cole).

Molecular Model Set

Homework: During the term, weekly reading assignments and homework problems from F&F and C&S will be assigned. Homework problems from F&F will not be collected and it is your responsibility to work on these problems. However, problems from C &S will be collected and graded. Note that literature references are given as the solutions to the C&S homework problems. This is to encourage you to look up the cited journal articles and find the answers to the problems yourselves. Being able to locate and decipher organic journal articles will be a regular part of the "reading assignments".

Asymmetric Synthesis Paper: You will choose an asymmetric synthesis article from any of the 1997 organic chemistry journals (JACS, JOC, Tet. Lett., Tetrahedron, Tetrahedron-Asymmetry etc..) and write a paper on it. The paper should be written so that any student who has completed one year of organic chemistry will be able to understand the article. Prof. Lee must approve your journal article by March 5th and the final paper is due on April 23rd.

"Molecule of the Week": To encourage more current literature reading and exposure to "chemistry in everyday life", an interesting organic molecule will be presented by a student each week. One of you will spend some time at the libraries (Simmons, MCP, Snell etc.) and research different aspects of the molecule (i.e. structure, synthesis, use, history etc.) and present them to the class in a 10 minute informal presentation. Everyone in the class will participate in this assignment and your turn will come up every "x" weeks depending on the class size.

Quizzes & Exams: There will be one exam and a final. In addition, there will be a couple of announced quizzes per unit. The quizzes will cover the reading, homework assignments, and lecture notes.

External Seminar: You are required to attend one external seminar and hand in your seminar notes. You can choose any organic or biochemistry seminar from the local universitiesí (BC, BU, NE, MIT, Harvard, Brandeis etc.) chemistry department seminars. You can search the Web or see the back of Nucleus for announcement of current seminar speakers and their topic.

Grades:

1 Hour Exam

100 pts

Final Exam

250 pts

Quizzes

150 pts

Carey and Sundberg HWís

150 pts

"Molecule of the week"

100 pts

Synthesis Paper

200 pts

External Seminar

50 pts

Total

1000 pts

 

Syllabus and Lecture outline

 

Unit 1: Review and Introduction of Chirality and Stereochemistry

Week1: review stereochemistry from F&F: enantiomers, diastereomers, meso compounds, assigning absolute configuration, optical activity.

Week 2: chiral compounds with nitrogen, sulfur, and phosphorus chiral centers; axially chiral compounds; prochirality.

Unit 2: Determination of Enantiomeric Purity and Separation of Enantiomers

Week 3: determining enantiomeric purity using polarimetric methods,chromatographic methods (chiral GC and HPLC)

Week 4: determining enantiomeric purity using NMR: chiral derivatizing agents, chiral solvating agents, chiral lanthanide shift reagents

Week 5: separation of enantiomers: classical resolution, kinetic resolution, HPLC

Week 6: Exam I: Feb. 19, 1998 (Thurs.)

Unit 3: Strategies for the Formation of Chiral Compounds

Week 7: introduction to asymmetric synthesis; use of chiral starting materials-survey of chiral pool and synthetic examples

Week 8: chiral substrate controlled synthesis: Cramís rule, Felkinís model; syn vs. anti reductions, Grignard, Michael, hydrogenation, iodolactonization

Week 9: using chiral auxiliaries in asymmetric synthesis: introduction to asymmetric aldol reactions. review enolate chemistry; Z/E enolates, kinetic vs. thermodynamic enolates, Zimmerman/Traxler model

Week 10: Evanís reagent- alkylation and aldol reaction; SAMP/RAMP

Week 11: Pericyclic reactions: introduction, asymmetric Diels-Alder, Claisen

Unit 4: Asymmetric Reagents and Catalysts

Week 12: chiral reducing reagents

Week 13: enantioselective reduction of ketones using chiral catalysts and enzymes;asymmetric epoxidation

Unit 5: Asymmetric Total Synthesis

Weeks 14 & 15: TBA