Chemistry 634: Advanced Organic Chemistry – Synthesis and Reactivity
Fall 2010, University of Delaware
Syllabus
Lecture Tuesday and Thursday, 7-8:30 PM Brown Lab (BRL) 207
Professor Donald A. Watson
205 Lammot duPont
302-831-8728
dawatson@udel.edu
Office hour: Monday 1-2pm, LDL 205
Problem Session: Tuesday 8:30-9:30 PM, TBD. Students are strongly urged to attend.
Website: http://www.udel.edu/chem/dawatson/classes/Chem634_F10/Chem634_F10-home.html
Required Texts:
Strategic Applications of Names Reactions in Organic Synthesis. Kurti, L.; Czako, B.
Advanced Organic Chemistry, Part B: Reactions and Synthesis. Carey, F. A.; Sundberg, R. J.
Recommend Texts (Optional):
Advanced Organic Chemistry · Part A: Structure and Mechanisms Carey, F. A.; Sundberg, R. J.
March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 6th Edition Smith, M. B.; March, J.
Classics in Stereoselective Synthesis
Erick M. Carreira, Lisbet Kvaerno
The following texts will also be on reserve in the Chemistry Library (and are good books to consider owning if
you plan to continue in synthetic organic chemistry).
Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition Larock, R. C.
Stereochemistry of Organic Compounds Eliel, E.; Wilel, S. H.
Protective Groups in Organic Synthesis, 4th Ed, Greene and Wuts
rd
Transition Metals in the Synthesis if Complex Organic Molecules, 3 Ed, Hegedus, L. S.
The Logic of Chemical Synthesis, Corey, E. J.; Cheng, X.
Model Kit (required):
I do not care which brand you buy, as long as it is of reasonable quality. If you are looking for recommendations,
here are two (also check with the bookstore, Amazon, or the like):
HGS 4010/Student Set – Expensive but very nice (they are a smaller set of the same models I use – I like them
because they are pretty rigid. Be warned, however, they tend to be fragile).
http://www.maruzen.info/hgs/catalog/product_info.php?cPath=11&products_id=596
Darling Models – Cheaper, but very floppy (which is not great for studying stereochemistry).
http://www.darlingmodels.com/item--KIT-1-ISBN-0-9648837-1-6-Plastic-Box-Organic-Inorganic-Organometallic-kit_1_plastic_student.html
Grading
Breakdown:
Midterm Exam 300 points, 30%
Final Exam 300 points, 30%
Final Project (Written) 150 points: 15%
Final Project (Presentation) 150 points: 15%
Problem Sets 100 points, 10%
Total: 1000 points
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Approximate Class Outline (exact dates of topics may vary with class progress):
Week 1
Week 2
Week 3
Week 4
Week 5
Week 6
Week 7
Week 8
Week 9
Week 10
Week 11
Week 12
Week 13
Week 14
Week 15
Finals Week
Aug 31
Sept 2
Sept 7
Sept 9
Sept 14
Sept 16
Sept 21
Sept 23
Sept 28
Sept 30
Oct 5
Oct 7
Oct 12
Oct 14
Oct 19
Oct 21
Oct 26
Oct 28
Nov 2
Nov 4
Nov 9
Nov 11
Nov 16
Nov 18
Nov 23
Nov 25
Nov 30
Dec 2
Dec 4
Dec 7
Lecture 1
Lecture 2
Lecture 3
Lecture 4
Lecture 5
Lecture 6
Lecture 7
Lecture 8
Lecture 9
Lecture 10
Lecture 11
Lecture 12
Lecture 11
Lecture 12
Lecture 13
Lecture 14
Lecture 15
Lecture 16
Lecture 17
Lecture 18
Lecture 19
Lecture 20
Lecture 21
Lecture 22
No Class
Lecture 23
Lecture 24
Saturday
Introduction, Arrow Pushing, Retrosynthesis
Electronic Databases and Searching the Literature
Nuc. Substitution Chemistry
Carboxylate Chemistry
Nuc. Aromatic Sub. Chemistry
Introduction to Organometallic Chemistry
Transition Metal Catalyzed Cross Coupling Reactions
Protecting Groups
Alcohol/Ketone Oxidations
C=X Reductions
Radical Chemistry
Radical Chemistry
Enolate Chemistry
Enolate Chemistry
Midterm Exam
Aldol Reactions
Aldol Reactions
Aldol Reactions
Introduction to Organocatalysis
Alkene Synthesis and Reactivity
Alkene Oxidation
Alkyne Synthesis
C=C Reductions
Pericyclic Reactions
Pericyclic Reactions
Thanksgiving
Strained Rings
C–H and C–C Bond Activation, time allowing
Student Presentations, 9a-12p
Student Presentations
FINAL EXAM
Problem Sets:
There will be approximately 10 problem sets assigned over this semester. They will total 100 point. Problem sets
will graded for completeness only, in 5 point increments. If you work all of the problems, you will get full credit. A
key will be posted each week and we will discuss the solutions after class on Tuesdays. You are responsible for
making sure that you understand the correct answers once the key is posted. You are free to work in study groups
when working on the problem sets, but each student must turn in their own work.
Do not use Beilstein, Scifinder or other search engines to look up answers on the homework unless specifically
asked. You will not have these tools when you take the exams (nor on interviews when you look for a job in a few
years), so you are best served by actually learning the material.
Problem sets will be due at the beginning of class on the day that is assigned. Late problem sets will not be
accepted as we may discuss the answers in class after it is due.
For problem sets, you will occasionally be asked to design synthetic routes to target compounds starting with
commercially available materials. For the purpose of this class, please limit these to chemicals that are listed in the
catalogs of Acros, Aldrich, Fisher, Strem, Alfa-Asear, or TCI. (These are the most common suppliers for academic
chemist).
Exams:
Exams will be closed book, closed note, and model set are not allowed. Exams will cover lecture material, problem
sets, assigned reading, as well as current literature discussed in class.
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Final Project:
For the final project, students will be asked to review a method or topic from the current organic chemical literature.
A list of possible topics will be distributed early in the semester and students will be allowed to choose topics shortly
thereafter. The project will consist of two parts.
First, each student will write a 3 page review article covering the most important aspects and references from the
assigned topic. This should be formatted as a JACS communication article. The reviews will be due in class on
rd
Nov. 23 . Please submit both a paper and electronic copy (via email). The reviews will be compiled and disturbed
to the class at the end of the semester.
th
Second, at the end of the semester, we will hold a mini-symposium on Saturday, Dec 4 from 9am-12pm.
Each student will present a 10-minute PowerPoint lecture in which they will teach the assigned topic to the class.
The date for the symposium will be determined during the semester. Any presentations that can not be fit in on
th
Saturday, will be finished during class on Dec. 7 .
Regrades:
All requests for regrades must be submitted in writing within 24 hours of the material being returned. Please note,
the entire exam will be regraded – if grading errors are found the final grades may be higher or lower than original
score. Also note, photocopies may be made prior to returning exams. If answers are altered, it will be obvious and
provable (see below).
Learning Objectives:
After successful completion of this class, students should:*
1) Understand principles of retrosynthesis and be able to plan synthetic routes to complex organic molecules.
(1,2)
2) Understand absolute and relative molecular stereochemistry and its importance in synthetic chemistry. (1)
3) Understand the use, installation and removal of protecting groups in organic synthesis. (1)
4) Be familiar with the methods and reactivity associated with alkyl groups, carbonyl groups, enolates, alkene,
alkynes, amines, amides, esters, ethers, aromatic rings, and strained rings. (1)
5) Be familiar with nucleophilic substitution chemistry, radical chemistry, methods for oxidation and reduction,
elementary organometallic chemistry as it pertains to organic synthesis, pericyclic reactivity, asymmetric
catalysis, and functional group interconversion. (1)
6) Be familiar with uses and applications of major electronic databases used in organic chemistry. (3,5)
7) Be familiar with major journals and publications pertaining to synthetic organic chemistry. (3,5)
8) Organize and review chemical literature in a topic area and present in clear and concise written and oral
formats. (3,4,10)
Academic Dishonesty
Academic dishonesty will not be tolerated. Not only is such behavior unethical, but also cheating in this class will
result in you not learning material that will be critical to your chosen career path. Simply put, learn this material; you
will need it to be a functional synthetic chemist. Please review the University of Delaware’s Academic Dishonestly
Policy, which can be found at http://www.udel.edu/stuguide/09-10/code.html#honesty. On assigned problem sets,
study groups are allowed, but each person must turn in their own work.
Plagiarism is as using someone else’s words or ideas without acknowledgment and most often results uncited
quoting or paraphrasing. Plagiarism is a serious form of academic dishonesty. For the written review assignments
in this class, make sure to properly cite any sources. For more information, please see:
http://www.english.udel.edu/wc/student/handouts/plagiarism.html
*Parenthetical numbers correspond to departmental learning goals found at www.udel.edu/chem.goals.html.
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Important Online Resources (Please see additional pdf handout).
UDel Chemistry Library Homepage: http://www2.lib.udel.edu/branches/chem.htm
Reaction and Structure Searching:
Scifinder: http://www2.lib.udel.edu/database/scifind.html
Reaxys: https://www.reaxys.com/reaxys/secured/start.do
Citation Searching:
Web of Science: http://apps.isiknowledge.com/
General Chemical Procedures:
Science of Synthesis: http://www.science-of-synthesis.com.proxy.nss.udel.edu/thiemechemistry/sos/prod/user/index.html
Listing of review articles complied by Phillip Kocienski (most useful with Endnote format):
Synthesis Reviews: http://www.thieme-chemistry.com/en/products/journals/supplements/synthesisreviews.html
Chemical Suppliers (maybe useful on problem sets):
Aldrich: http://www.sigmaaldrich.com/united-states.html
Acros: http://www.acros.com/
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Mechanism and Synthesis
Understanding a reaction at a mechanistic level is necessary in order to be able to apply it to effect the desired
outcome. If you do not know how it works, you might not understand what can go wrong, or how to fix it when it
does. If you encounter a mechanism that you do not understand – take the time to work out a reasonable
mechanism. It is assumed that you are familiar with elementary arrow pushing and we will not be covering this in
class in any depth. For those that need a refresher, the following approach is very useful.
The 12-step guide to arrow pushing (adapted from Prof. Keith Woerpel, UC Irvine):
1) Electrons flow from sites of high electron density to sites of low electron density (show arrows accordingly).
2) Balance the equation. It helps.
3) Don’t violate basic rules of physics.
a. Converse mass and energy (see rule 2)
b. Conserve charge
4) Three Arrow Rule: Don’t push more than 3 arrows at one time
5) Draw out all intermediates.
a. It may seem tedious at time, but it will avoid mistakes and often reveal new insights.
b. 3-D depictions may help. Use models if needed.
6) Use your lone pairs (often the site of FMO’s).
7) All steps are, in principle, reversible.
8) Contemplate your options and carry each to its conclusion before discarding (this is seriously useful
advice).
9) The correct mechanism gives the observed product (should not be taken to mean that all mechanisms that
lead to the product are necessarily correct).
10) Use connectivity to tell you how the puzzle fits together.
a. Number atoms logically
b. “Principle of least action” usually holds.
11) Always identify the nucleophiles and electrophiles at each step.
a. At times it may be useful to substitute oxidants and reductants above.
12) Work backwards from the product to the likely precursors.
Basic Guide to Retrosynthetic Analysis
1) Maximize convergence
2) Minimize steps by exploring multiple options before deciding on a plan (avoid FGI and protecting groups, if
possible)
3) Add functional groups if they can lead to a simplifying disconnection
4) Disconnect stereocenters (clear stereocenters) where possible
5) C-C and C-CX bonds usually make good disconnections
6) Minimize medium and large rings formation
7) Disconnect unstable functional groups early in retrosynthesis
8) Recognize embedded symmetry
9) ID embedded complex molecules (particularly chiral pool)
10) Use topology to your advantage (particularly in caged molecules, make a model before starting)
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