Chemistry 242a: Chemical Synthesis
Fall 2009
Sarah E. Reisman
office: 349 Crellin
lab: Church Basement
phone: (626) 395-6044
office hours: M Tu Th F, 10-11 am or by appointment
email: reisman@caltech.edu
course website: http://reismangroup.caltech.edu/242a_Website/242a_Home.html
Teaching Assistants:
John Yeoman
Lindsay Repka
Jay Codelli
email:
yeomanjo@caltech.edu
lrepka@caltech.edu
jcodelli@caltech.edu
desk:
20 Church
16 Church
20 Church
phone:
x 6061
x 6061
x 6061
Lectures: 147 Noyes (28 total)
M W F 9:00 a.m. September 30 – December 4, 2009.
No class Friday, November 27, 2009 (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”
2. Warren, S. “Designing Organic Syntheses: A Programmed Introduction to the Synthon Approach”
Optional Texts: (all are excellent reference resources and highly recommended)
1. March, J.; Smith, M.B. “Advanced Organic Chemistry, 6th Edition”
2. Corey, E. J.; Cheng, X.-M. “The Logic of Chemical Synthesis”
3. Nicolaou, K. C. “Classics in Total Synthesis” vol.'s 1 (w/Sorensen) and 2 (w/Snyder)
4. Hegedus, L. S. “Transition Metals in the Synthesis of Complex Organic Molecules, 3rd Edition”
5. Greene, T. W.; Wuts, P. G. M. “Protective Groups in Organic Synthesis”
6. Hudlicky, T.; Reed, J.W. “The Way of Synthesis”
The above text books are available on reserve in Millikan Library, and can be purchased through the Caltech
AdoptaText website:
https://access.caltech.edu/adoptatext/home
Model Sets:
HGS molecular model sets are available in the Crellin stockroom from Joe Drew. Additional versions are
available at the following website:
http://www.maruzen.info/hgs/catalog/index.php?cPath=11
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).
Chemistry Library Web Site:
http://library.caltech.edu/collections/chemistry.htm
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. You
must complete the assigned pages by the specified date in this syllabus. This work must 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.
Synthesis Project:
Each student will be assigned a molecule for which they must design and propose a total synthesis. A 1-page
schematic rough draft your retro-synthetic analysis will be due Friday, October 30th. A two page written
proposal will be due on Monday, November 30th. Each student will give a 7-minute presentation of his or her
synthetic route during either the December 1 st (Tuesday) or 3rd (Thursday) evening session. Molecule
assignments and further details will be distributed on Friday, October 2nd.
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.
Exams:
There will be two midterm exams and a comprehensive final. The exams will be take-home and in some cases
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, October 26, 2009 - 9 AM
Monday, November 23, 2009 - 9 AM
Final Exam Due Date: Friday, December 11, 2009 - 9 AM
Course Grade:
The course grade will be based on midterm exams (40%), problem sets and discussion (10%), synthesis proposal
(15%), and the final exam (35%). Extra credit will be awarded to undergraduates for participation in problem
discussions (up to 10%).
Course Syllabus: Chem 242a
class
date
topic
course work due
1W
2F
9/30
10/2
retrosynthetic analysis
synthesis Friday
PS #1 due (10/1)
3M
4W
5F
10/5
10/7
10/9
conformational analysis
conformational analysis
synthesis Friday
PS #2 due (10/8), Warren p. 1-75
6M
7W
8F
10/12
10/14
10/16
oxidation
oxidation
stereoselective oxidation
PS #3 due (10/15), Warren p. 77-130
9M
10W
11F
10/19
10/21
10/23
synthesis Monday
stereoselective oxidation
stereoselective oxidation
12M
13W
14F
10/26
10/28
10/30
hydrogenation
stereoselective hydrogenation
synthesis Friday
15M
16W
17F
11/2
11/4
11/6
carbonyl reduction
carbonyl addition
synthesis Friday
PS #5 due (11/5), Warren p. 173-200
18M
19W
20F
11/9
11/11
11/13
enolates
enolate alkylation
synthesis Friday
PS #6 due (11/12), Warren p. 201-254
21M
22W
23F
11/16
11/18
11/20
aldol
asymmetric aldol
stereoselective allylation
24M
25W
11/23
11/25
stereoselective allylation
synthesis Wednesday
midterm #2 due
26M
11/30
metal carbenoids
syn. prop due; presentations on 12/1
and 12/3
27W
28F
12/2
12/4
transition metal cat. C–C bond formation
synthesis Friday
12/11
PS #4 due (10/22), Warren p.131-172
midterm #1 out
midterm #1 due
syn. prop retro due
PS #7 due (11/19)
midterm #2 out
final exam out
final exam due
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, 6th Edition"
J. J. Li, "Name Reactions"
Websites:
http://www.organic-chemistry.org/namedreactions/
http://www.monomerchem.com/display4.html
10/2
Aldol reaction
Mannich reaction
Diels-Alder reaction
Alder ene reaction
Michael addition
Robinson annulation
Dieckmann condensation
Grignard reaction
Swern oxidation
Jones oxidation
10/9
Fischer indole synthesis
Pummerer rearrangment
Beckmann rearrangement
Curtius rearrangement
Hofmann rearrangement
Bamford-Stevens reaction
10/16
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
10/23
Claisen rearrangement
Cope rearrangement
Ireland-Claisen rearrangement
Oxy-Cope rearrangement
Overman rearrangement
Aza-Cope Mannich reaction
Mislow-Evans rearrangement
Prins-Pinacol rearrangement
10/30
Brook rearrangement
Corey-House reaction
Julia-Lythgoe olefination
Wharton alkene synthesis
Peterson olefination
Chugaev Reaction
Saegusa-Ito oxidation
11/6
Arndt-Eistert homologation
Wolff rearrangement
Neber Rearrangement
Henry reaction
Simmons-Smith reaction
Wolff-Kischner Reduction
11/13
Knoevenagel reaction
Mukaiyama Aldol reaction
Sakurai reaction
Reformatsky reaction
Favorskii rearrangement
11/20
Krapcho Decarboxylation
Finkelstein reaction
Hunsdiecker reaction
Mitsunobu reaction
Strecker reaction
Barton-McCombie Deoxygenation
11/27
Grubbs olefin metathesis
Stille reaction
Suzuki reaction
Heck reaction
Negishi reaction
Sonagashira reaction
Tsuji-Trost allylation