Chemistry 242a: Chemical Sy nthesis
Fall 2014
Sarah E. Reisman
office: 301B Schlinger
lab: 311 Schlinger
phone: (626) 395-6044
office hours: M F, 10-11 am or by appointment
email: reisman@caltech.edu
Teaching Assistants:
Nick Cowper
Arthur Han
Denise Grunenfelder
Blake Daniels
email:
ncowper@caltech.edu
ahan@caltech.edu
dgrunenf@caltech.edu
bdaniels@caltech.edu
desk:
315 Schlinger Lab
305 Schlinger Lab
305 Schlinger Lab
315 Schlinger Lab
phone:
x6061
x6061
x6061
x6061
Lectures: 147 Noyes (28 total)
M W F 9:00 a.m. September 29 – December 5, 2014.
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, 6th 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, 3rd 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:
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. 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:
http://www.cce.caltech.edu/master-calendar/month
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, 2014 – 9 AM
Final Exam Due Date: Friday, December 12, 2014 – 9 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).
Course Syllabus: Chem 242a
class
date
Topic
1M
2W
3F
9/29
10/1
10/3
introduction and synthetic strategy
conformational analysis
synthesis Friday
4M
5W
6F
10/6
10/8
10/10
conformational analysis
oxidation
synthesis Friday
7M
8W
9/10F*
10/13
10/15
10/17*
oxidation
stereoselective oxidation
stereoselective oxidation, synthesis Friday
*lecture will be 8-10 am
11M
10/20
10/22
10/24
hydrogenation
no lecture
Institute Academic Holiday
PS #1 due (10/23), Warren p.131-172,
14M
15W
10/27
10/29
10/31
stereoselective hydrogenation
synthesis Wednesday
no lecture
PS #2 due (10/30), Warren p.131-172,
midterm out
16M
17W
18F
11/3
11/5
11/7
carbonyl reduction
carbonyl addition
enolates
19M
20W
21F
11/10
11/12
11/14
enolate alkylation
aldol
aldol
22W
23/24F*
11/17
11/19
11/21*
no lecture
stereoselective aldol
synthesis Friday
11/24
11/26
11/28
stereoselective aldol
allylation/crotylation
no lecture – Thanksgiving Break
12/1
12/3*
12/5
12/8
12/9
12/12
stereoselective allylation
metal carbenoids
synthesis Friday
12/13F
25M
26W
27W*
28F
notes/course work due
project assignments distributed
Warren p. 1-75
midterm due (11/3) at 9 a.m.
PS #3 due (11/13), Warren p. 201-254
PS #4 due (11/20)
*lecture will be 8-10 am
*lecture will be 8-10 am
PS #5 due (12/4)
final exam out
project due 5 p.m.
final exam due 9 a.m.
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
10/3
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