Syllabus
This course will examine the tools - both theoretical and experimental - that the modern organic chemist has at his or her disposal for elucidating mechanisms.
Strongly Recommended Text:
Anslyn, E. V.; Dougherty, D. A. Modern Physical Organic Chemistry. University Science Books, 2006.
Additional Useful References, Not Required:
• Grossman, R. B. The Art of Writing Reasonable Organic Reaction Mechanisms, Springer, 2002 (hardback) and 2010 (paperback).
• Fleming, I. Molecular Orbitals and Organic Chemical Reactions. Wiley, 2010 (both a reference edition and student edition are available)
• Alabugin, I. Stereoelectronic Effects: A Bridge Between Structure and Reactivity. Wiley, 2016.
• Sundberg, R. J.; Carey, F. A. Advanced Organic Chemistry, Part A: Structure and Mechanism, 4th Edition. Kluwer/Plenum Press, 2000.
• Gómez-Gallego, M.; Sierra, M. A. Organic Reaction Mechanisms–40 Solved Cases. Springer, 2004.
• Isaacs, N. Physical Organic Chemistry, 2nd Edition, Addison-Wesley-Longman, 1995
• Fleming, I. Frontier Orbitals and Organic Chemical Reactions. Wiley, 1996.
• Carpenter, B. K. Determination of Organic Reaction Mechanisms. Wiley, 1994.
• Smith, M. B.; March, J. March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 6th Edition. Wiley, 2007.
• Lowry, T. H.; Richardson, K. S. Mechanism and Theory in Organic Chemistry, 3rd Edition. Harper Collins, 1987.
• Quinkert, G.; Egert, E.; Griesinger, C. Aspects of Organic Chemistry: Structure. VCH, 1996.
• Moss, R. A.; Platz, M. S.; Jones, M. Reactive Intermediate Chemistry. Wiley, 2004.
• Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds. Wiley, 1994.
• Young, D. Computational Chemistry: A Practical Guide for Applying Techniques to Real World Problems.Wiley, 2001.
A Great Source of Practice Problems:
http://evans.rc.fas.harvard.edu/problems/index.cgi
The IUPAC Glossary of Terms Used in Physical Organic Chemistry:
My Expectations:
A working knowledge of undergraduate Organic Chemistry is expected.
This class is not about memorization. It is about developing analytical thinking and problem solving skills.
By the end of the quarter, I expect the following:
When given an experimental observation on a particular reaction, you should be able to:
(1) write down a reasonable arrow-pushing mechanism for the reaction
(2) decide whether existing theories can explain the observed reactivity
(3) design experiments to test your proposed mechanism/explanation
(4) evaluate the validity/plausibility of others' explanations
Outline (subject to change):
I. GENERATING MECHANISTIC HYPOTHESES
1. Introduction to arrows
2. Lightning fast survey of organic reactivity (10.1)
• carbanions
• carbocations
• carbenes
• radicals
3. Strategies and “rules” for arrow-pushing
II. REASONABILITY PART 1 – FUNDAMENTAL CONCEPTS
1. Energy
• types: E, H, G, S
2. What do you mean by stability?
• kinetic v. thermodynamic
• isodesmic equations
3. Potential energy surfaces
• what the axes mean
• problems with “rate-determining” and “selectivity-determining”
• Curtin-Hammett principle
• Hammond postulate and Bell-Evans/Polanyi principle
• concertedness and synchronicity; Moore-O’Ferral/Jencks plots
4. Transition state theory
5. Dynamic effects
• dynamic matching
• rate enhancement; A --> B
• selectivity control; A --> B --> C or D
• post-transition state bifurcations: A --> C or D
6. Multiple possible reasonable mechanistic proposals
• norbornyl cation dimethylcyclopentenyl cation
III. EXPERIMENTS TO TEST MECHANISTIC PROPOSALS
1. Point Group Symmetry
• symmetry elements and operations, point groups
• chirality and topicity
• symmetry as a mechanistic tool
• musings on symmetry and efficiency
2. Introduction to chemical kinetics
3. Solvent effects
4. Kinetic isotope effects
• primary
• secondary normal and inverse
• tunneling
5. Linear Free Energy Relationships (Hammett plots)
IV. REASONABILITY PART 2 – A MOLECULAR ORBITAL-BASED DEEP DIVE
1. What does the Schrodinger equation mean?
2. Simple Huckel theory, i.e., doing quantum mechanics by hand
3. Frontier MO theory, i.e., donor-acceptor interactions
4. Aromaticity
5. Pericyclic reactions
