Chemistry 242a: Chemical Sy nthesis Fall 2014

Transcription

1 Chemistry 242a: Chemical Sy nthesis Fall 2014 Sarah E. Reisman office: 301B Schlinger lab: 311 Schlinger phone: (626) office hours: M F, am or by appointment [email protected] Teaching Assistants: desk: phone: Nick Cowper [email protected] 315 Schlinger Lab x6061 Arthur Han [email protected] 305 Schlinger Lab x6061 Denise Grunenfelder [email protected] 305 Schlinger Lab x6061 Blake Daniels [email protected] 315 Schlinger Lab x6061 Lectures: 147 Noyes (28 total) M W F 9:00 a.m. September 29 December 5, No class Friday, November 28, 2014 (Thanksgiving recess) Recitation: Tu 7 9 p.m. Problem Set Tutorial: Th 7 9 p.m. Required Texts: 1. Kürti, L.; Czakó, B. Strategic Applications of Named Reactions in Organic Synthesis Optional Texts: (all are excellent reference resources and highly recommended) 1. Warren, S. Designing Organic Syntheses: A Programmed Introduction to the Synthon Approach 2. March, J.; Smith, M.B. Advanced Organic Chemistry, 6 th Edition 3. Corey, E. J.; Cheng, X.-M. The Logic of Chemical Synthesis 4. Nicolaou, K. C. Classics in Total Synthesis vol.'s 1 (w/sorensen) and 2 (w/snyder) 5. Hegedus, L. S. Transition Metals in the Synthesis of Complex Organic Molecules, 3 rd Edition 6. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis 7. Hudlicky, T.; Reed, J.W. The Way of Synthesis 8. Carreira, E.M.; Kvaerno, L. Classics in Stereoselective Synthesis 9. Corey, E. J.; Kurti, L. Enantioselective Chemical Synthesis The above textbooks are available on reserve in Millikan Library, and can be purchased through the Caltech AdoptaText website: Model Sets: HGS molecular model sets are available in the Crellin stockroom from Joe Drew. Additional versions are available at the following website: The Stereochemistry 4010/Student set is a cost effective option. Students are strongly encouraged to purchase at least one model set. Other relevant texts and references: 1. Larock, R. C. "Comprehensive Organic Transformations" 2. The Merck Index 3. The Aldrich, Strem, and Acros Catalogs 4. Beilstein/Discovery Gate, Sci-Finder (Chemical Abstracts Service) and Web of Science online. For a complete list of on-line resources, see the Caltech Library link on the next page. 5. Paquette, L. A. "Encyclopedia of Reagents for Organic Synthesis, 8 Volume Set" (now available online through the e-eros link from the Caltech Library homepage).

2 Chemistry Library Web Site: Problem Sets: Problem Sets will be distributed on Fridays and are due by 7:00 p.m. on the following Thursday night; a weekly problem session will be held on Thursday evenings in 147 Noyes beginning at 7:00 pm. Students will be expected to discuss their answers to the problems at the board. This will be the only opportunity to see the solutions to the problem sets. Reading selections from Warren s Designing Organic Syntheses are assigned in the syllabus weekly. Though optional, you are highly recommended to complete the assigned pages by the specified date in this syllabus. This work should be completed individually. The evening sessions are optional for undergraduates enrolled in 242a, however attendance and participation is strongly encouraged. Extra credit will be awarded to undergraduates for participation. Original Proposal: To be discussed in class. Name Reactions: There are a number of key reactions in organic chemistry that have become identified by a name (either a person or a specific transformation). Knowledge of these reactions is fundamental to your success in this class. You should learn each of the reactions listed by the date indicated on the name reactions handout at the end of this syllabus. They will appear on exams and problem sets in a timely fashion. Current Literature: The state of chemical synthesis is highly dynamic and changes on a daily basis. In order to keep pace with new developments, part of the requirement of this course will be to stay abreast of new and particularly relevant publications in the primary synthetic literature. Students will be required to read the primary literature, and distill out pertinent developments, and report them back to the class. This important exercise will take place during the Thursday problem sessions. Members of the class will be given a playing card, and during the session a deck of cards will be cut and two students with the matching cards will present a synopsis of a relevant communication from a recent issue of J. Am. Chem. Soc., Angew. Chem. Int. Ed., Org. Lett., J. Org. Chem., or Tetrahedron Lett. Be sure to include the primary author, institution affiliation, and proper reference in your description. This serves the purpose of not only keeping the class current, but also will help students to launch their own database of relevant chemical literature. If your teaching schedule permits, you should also plan to attend the OCS seminars. The seminars are typically held on Wednesday afternoons at 4 pm. For specific dates, see:

3 Exams: There will be a midterm exam and a comprehensive final. The exams will be take-home and in some sections outside resources may be consulted (e.g., class notes). Please follow the instructions precisely as they are given on each exam. Exam Due Dates: Monday, November 3, AM Final Exam Due Date: Friday, December 12, AM Course Grade: The course grade will be based on midterm exam (30%), final exam (30%), problem sets and discussion (20%), proposal project (20%). Extra credit will be awarded to undergraduates for participation in problem discussions (10% based on attendance, all or nothing).

4 Course Syllabus: Chem 242a class date Topic notes/course work due 1M 9/29 introduction and synthetic strategy 2W 10/1 conformational analysis 3F 10/3 synthesis Friday 4M 10/6 conformational analysis project assignments distributed 5W 10/8 oxidation Warren p F 10/10 synthesis Friday 7M 10/13 oxidation 8W 10/15 stereoselective oxidation 9/10F* 10/17* stereoselective oxidation, synthesis Friday *lecture will be 8-10 am 11M 10/20 hydrogenation 10/22 no lecture 12/13F 10/24 Institute Academic Holiday PS #1 due (10/23), Warren p , 14M 10/27 stereoselective hydrogenation 15W 10/29 synthesis Wednesday PS #2 due (10/30), Warren p , 10/31 no lecture midterm out 16M 11/3 carbonyl reduction midterm due (11/3) at 9 a.m. 17W 11/5 carbonyl addition 18F 11/7 enolates 19M 11/10 enolate alkylation 20W 11/12 aldol PS #3 due (11/13), Warren p F 11/14 aldol 11/17 no lecture 22W 11/19 stereoselective aldol PS #4 due (11/20) 23/24F* 11/21* synthesis Friday *lecture will be 8-10 am 25M 11/24 stereoselective aldol 26W 11/26 allylation/crotylation 11/28 no lecture Thanksgiving Break 12/1 stereoselective allylation 27W* 12/3* metal carbenoids *lecture will be 8-10 am 28F 12/5 synthesis Friday PS #5 due (12/4) 12/8 final exam out 12/9 project due 5 p.m. 12/12 final exam due 9 a.m.

5 Name Reactions Below are some name reactions that are of importance in synthetic organic chemistry. You are expected to know the overall transformation and a reasonable mechanism for each reaction by the date indicated. Good references: L. Kürti, B. Czakó, Strategic Applications of Named Reactions in Organic Synthesis J. March, M.B. Smith, "Advanced Organic Chemistry, 6 th Edition" J. J. Li, "Name Reactions" Websites: /3 aldol reaction (technically not named) Mannich reaction Diels-Alder reaction Alder ene reaction Michael addition Robinson annulation Dieckmann condensation Grignard reaction Swern oxidation Jones oxidation 10/10 Fischer indole synthesis Pummerer rearrangement Beckmann rearrangement Curtius rearrangement Hofmann rearrangement Bamford-Stevens reaction Ritter reaction 10/17 Claisen rearrangement Cope rearrangement Ireland-Claisen rearrangement Oxy-Cope rearrangement Overman rearrangement Aza-Cope Mannich reaction Mislow-Evans rearrangement Prins-Pinacol rearrangement Baeyer-Villiger oxidation 10/24 Baeyer-Villiger oxidation Rubottom oxidation Oppenauer oxidation Meerwein-Ponndorf-Verley reduction Wacker oxidation Tamao-Fleming oxidation Tischenko reduction Luche reduction Wittig reaction Horner-Wadsworth-Emmons reaction 10/31 Brook rearrangement Corey-House reaction Julia-Lythgoe olefination Wharton alkene synthesis Peterson olefination Chugaev Reaction Saegusa-Ito oxidation 11/7 Arndt-Eistert homologation Wolff rearrangement Neber Rearrangement Henry reaction Simmons-Smith reaction Wolff-Kischner Reduction 11/14 Knoevenagel reaction Mukaiyama Aldol reaction Sakurai reaction Reformatsky reaction Favorskii rearrangement 11/21 Grubbs olefin metathesis Stille reaction Suzuki reaction Heck reaction Negishi reaction Sonagashira reaction Tsuji-Trost allylation 11/28 Krapcho Decarboxylation Finkelstein reaction Hunsdiecker reaction Mitsunobu reaction Strecker reaction Barton-McCombie Deoxygenation