Chemistry 335 – Synthetic Methods in Organic Chemistry
Spring 2017 • 20531 • A01
Prof Jeremy Wulff • [email protected]
Lectures: Tuesdays, Wednesdays and Fridays 11:30am–12:20pm, MacLaurin D288
Office Hours / Drop-In Times: Mondays & Fridays 1–2pm, Elliott 038
Course Website: web.uvic.ca/~chem335/
Textbook: The Art of Writing Reasonable Organic Reaction Mechanisms, 2nd Ed., Robert Grossman
Available online through UVic subscription at: http://link.springer.com/book/10.1007/b97257
Design of syntheses in aliphatic, aromatic and some biomolecules. Aliphatic systems; carbanions,
conjugated carbonyl compounds, amines in syntheses, functional group modifications. Aromatic
systems; aromatic substitution processes, reactive substrates (phenols, amines), polynuclear aromatics.
Biomolecules: synthesis and modification of heterocycles and carbohydrates.
How did we get here? What are we doing? Where are we going?
In Chemistry 231 you learned the vocabulary of organic chemistry: nucleophiles, electrophiles, SN1, E1,
SN2, E2, etc. You also learned some important concepts like stereochemistry and reaction mechanism.
Finally, you learned the difference between polar reactions, radical reactions, and acid base reactions.
In Chemistry 232 you vastly expanded your repertoire of reactions, learning about electrophilic
aromatic substitution, Diels-Alder reactions, carbonyl additions and substitutions, aldol reactions, and
a few of the reactions that happen with amines.
In Chemistry 335, the goal will be to achieve an advanced understanding of the reactivity of organic
molecules. You will learn the fundamental principles that guide chemoselective, regioselective, and
stereoselective chemical reactions, and you will learn how to use these principles to plan the synthesis
of relatively complex, bioactive molecules. To facilitate these goals, the course will be taught from the
perspective of reaction mechanism; this will allow you to understand each of the reactions that we
discuss (without memorizing!), while giving you the tools you need to understand and predict any
organic reaction – even one that you’ve never seen before!
Skills and knowledge that you gather in this course will be useful for future applications in synthetic
chemistry (particularly pharmaceutical synthesis and polymer synthesis) and biochemistry (particularly
for understanding enzymatic transformations and biosynthesis), and will provide an important
grounding to understand the role of chemistry in society.
Students who are particularly keen on complex molecule synthesis and want to know more about how
to make molecules should consider taking Chemistry 432. Those who are more interested in
understanding the function of biologically active compounds should consider taking Chemistry 437. The
present course provides a useful preparation for both future courses.
– page 1 –
Learning Objectives:
At the conclusion of this course, you should be able to:
1. Predict the products, reagents or reactants for all chemical transformations covered in class.
These will include C-C single bond, C=C double bond, C-X bond formations and eliminations,
reductions, oxidations, protecting group transformations, and other functional group
interconversions.
2. Draw a reasonable arrow-pushing mechanism (being careful to denote stereochemistry where
relevant) for all reactions covered in class, and for related transformations that you may not have
explicitly been exposed to.
3. Use knowledge of reactivity and structure to rationalize regiochemical and stereochemical
consequences of reactions.
4. Identify the “best” reactions to accomplish desirable C-C/C-X bond forming reactions, taking into
account selectivity issues.
5. Use your expertise to plan the synthesis of useful small molecules. These may include molecules
with desirable biological activity (i.e. drugs) or molecules that are useful in the construction of
materials (e.g. monomers for use in crafting novel polymers).
Textbook:
The text for this course is ‘The Art of Writing Reasonable Organic Reaction Mechanisms, 2nd Edition’ by
Robert Grossman. It does not cover all aspects of this course, but presents a very readable primer on
the part of the course that students have the most trouble with: using curved arrows and mechanism to
understand and exploit the various organic reactions that are discussed in Chemistry 335.
In addition to being much more readable than most textbooks, it also has the advantage of being very
inexpensive – even free if you are willing to read online. To access the online version of the text
(courtesy of UVic’s subscription to Springer) go here: http://link.springer.com/book/10.1007/b97257.
You may need to be at a UVic computer, or else use a virtual IP to access this content. You can download
a VPN if required from UVic’s computer services pages.
I strongly suggest that you source a hard copy of the textbook for yourself. You can order one online for
well under $100, and apparently can access a ‘MyCopy’ softcover version directly from the link above for
US $25.
Aside: A note about your textbook.
At frequent intervals, Grossman encourages you to refer to other books for review on drawing Lewis
structures, pushing electrons, drawing resonance structures, etc. This is kind of an annoying habit, but
don’t let it bother you too much. In every case, your second-year organic chemistry course provides the
necessary background. If you’ve forgotten something important from this earlier course, then by all
means go back and consult your textbook from that class. But don’t feel you need to buy the particular
book that Grossman is alluding to.
– page 2 –
Course Website:
Some additional content – powerpoint slides, answer keys, practice exams, etc. – are posted on the
course website which you can access at: web.uvic.ca/~chem335/. I particularly suggest that you review
the ‘Bad Reactions’ document there, which presents a convenient list of common errors made by
students of organic chemistry.
Examinations:
Evaluation for Chemistry 335 will be based upon three term tests, together with a final exam. The three
term tests together will be worth 50% of your final grade (i.e. each test is nominally worth 16.67%), and
the final exam is worth the remaining 50%. If you need to miss a term test (due to medical absence,
UVic-sanctioned sports team outing, etc.) then your term test grade will be taken from the average of
the two other tests. A note from your doctor or coach will be required. The dates for the term tests are:
Term test 1: Wednesday, February 1st
Term test 2: Wednesday, March 1st
Term test 3: Wednesday, March 29th
Grading:
Your final grade will be reported as a numerical percentage, in keeping with UVic’s policies on grade
reporting. Letter grades are derived from numerical percentages as follows:
A+
B+
C+
F
90-100%
77-79%
65-69%
< 50%
A
B
C
N
85-89%
A- 80-84%
73-76%
B- 70-72%
60-64%
D 50-59%
incomplete performance
Academic Integrity:
Instances of plagiarism will be dealt with as harshly as possible, within the confines of the University’s
academic integrity policy. (see: http://web.uvic.ca/calendar2011/FACS/UnIn/UARe/PoAcI.html) Having
said this, I strongly encourage you to work together on the assigned problems, and study together for
tests. Arguing with one another about the course material is extremely helpful in mastering the content
from Chemistry 335.
– page 3 –
Some “Rules” for Chemistry 335... before we get too deep into the material.
Rule #1. This is not a ‘redo’ of Chemistry 231 and 232.
While we will be reviewing certain aspects of the material from these earlier courses, the purpose of
Chem 335 is to introduce new material and take you deeper into the field of organic chemistry. Recall
and retention of the content from Chem 231 and 232 is therefore expected.
Rule #2. Read your textbook.
No, actually – read it! Don’t just look at the pictures, or skim a few sections. Start on page 1 (or
earlier; the preface is also quite useful) and read every word. Work through the examples provided. At
the end of each sentence, ask yourself whether you understand what the author is talking about. If not,
come talk to me in the drop-in times and we’ll work through it. Continue reading every word until
you’ve reached the end of the book. New for this year, we’ve chosen a textbook that is easy to read and
that doesn’t burden you with things you don’t need to know. So actually read the thing!
Rule #3. Reading is not enough.
To learn organic chemistry, you need to actually practice organic chemistry. Do the assigned
problems – especially the mechanism problems! Write everything out on paper. Push arrows. Think
about how electrons move. More than most other fields, organic chemistry is a skill rather than just a
topic. And you can’t learn skills without practicing. Don’t wait until the night before the exam to try and
learn the course. Instead, plan to practice organic chemistry at least three times per week, throughout
the duration of the course.
Rule #4. Your course material takes precedence over your textbook.
As good as your textbook is, there will occasionally be times where I’m going to say something in class
that directly contradicts something that’s written in it. Mostly this will be on issues of formalism (e.g. I
will be encouraging you to use equilibrium arrows where it is important for particular transformations;
Grossman avoids this by admitting that every reaction is technically reversible, then not worrying so
much about when you might care/not care about this reversibility). But occasionally it might crop up in
issues of fact as well. I will usually point out these differences when they occur, but may forget to do so
in the excitement of the lecture. Whenever these differences arise, I expect you to follow what I teach
you in class. For example, on exams you will be expected to show equilibrium arrows for steps that are
under equilibrium control, and show single reaction arrows for steps that are not.
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The Oaths of Good Mechanism
I, _________________, do solemnly swear, that when writing mechanisms for reactions in strongly
acidic solution, I will not invoke unreasonable negatively charged species.
I, _________________, do solemnly swear, that when writing mechanisms for reactions in strongly basic
solution, I will not invoke unreasonable positively charged species.
I, _________________, do solemnly swear, that I will push arrows from the nucleophile to the
electrophile, and never the reverse.
I, _________________, do solemnly swear, that I will never use H– as a leaving group, either explicitly or
by implication in any reaction mechanism.
I, _________________, do solemnly swear, that I will never make more than 4 bonds to carbon.
I, _________________, do solemnly swear, that I will never propose to carry a reactive functional group
(e.g. Grignard reagent, diazonium salt, acid chloride, carboxylic acid, alkyl aldehyde) though steps that
will trigger unwanted reaction with that functional group (e.g. alcohols and phenols will quench
Grignards, diazoniums decompose explosively upon heating, acid chlorides will react with water used in
an aqueous workup, carboxylic acids will quench carbanions and Wittig reagents, aldehydes with
adjacent protons are prone to self-condensation, etc.).
I, _________________, do solemnly swear, that I will carefully read the ‘Bad Reactions’ document on
the course webpage for more examples of things that will lose me marks on exams.
– page 5 –