Department of Chemistry and Chemical Biology
Harvard University

Science Center, 115A
1 Oxford St.
Cambridge, MA 02138
tel: 617-495-7125

Software Downloads:
Postdoctoral (Harvard University, present)
Research in organic methodology and computational chemistry
with Professor Eric N. Jacobsen

Doctoral (Harvard University)
Research in organic synthesis
with Professor David A. Evans

Undergraduate (University of Toronto)
Research in NMR spectroscopy of natural products
with Professor William F. Reynolds

Research Interests

My research is at the interface of physical and organic chemistry. I am interested in how organic chemistry can be understood, improved, or discovered using mechanistic principles. Past projects have involved the experimental and computational study of Michael, aldol, glycosylation and fluorination reactions, the prediction of chemical shifts using molecular dynamics, and the development of improved NMR methods for the measurement of carbon-13 isotope effects at natural abundance.

Teaching Interests

My teaching has focused on the creation of new courses on organic chemistry. My primary role is to teach advanced organic chemistry, which is partially a reinterpretation of Chem 206, the classic course taught by Professor David A. Evans. The course covers molecular orbital interactions, conformational analysis, stereochemistry, reactive intermediates, catalysis, and modern synthetic methods. I have also taught physical-organic chemistry, NMR spectroscopy, laboratory techniques, and introductory sophomore-level courses.


16. “Concerted Nucleophilic Aromatic Substitutions.”   Kwan, E.E.; Zeng, Y.; Besser, H.A.; Jacobsen, E.N.*   Nature Chem.  2018, 10, 917–923.  doi: 10.1038/s41557-018-0079-7.

15. “Macrocyclic Bis-Thioureas Catalyze Stereospecific Glycosylation Reactions.”   Park, Y; Harper, K.; Kuhl, N.; Kwan, E.E.; Liu, R.Y.; Jacobsen, E.N.*   Science.  2017, 355, 162–166.  doi: 10.1126/science.aal1875.

14. “Sensitive and Accurate 13C Kinetic Isotope Effect Measurements Enabled by Polarization Transfer.”   Kwan, E.E.*; Park, Y.; Besser, H.A.; Anderson, T.L.; Jacobsen, E.N.*   J. Am. Chem. Soc.  2017, 139, 43–46.  doi: 10.1021/jacs.6b10621.

13. “Mechanistic Studies and Radiofluorination of Structurally Diverse Pharmaceuticals with Spirocyclic Iodonium(III) Ylides.”   Rotstein, B.H.; Wang, L.; Liu, R.Y.; Patteson, J.; Kwan, E.E.; Vasdev, N.*; and Liang, S.H.*   Chem. Sci.  2016, 7, 4407–4417.  doi: 10.1039/C6SC00197A.

12. “Enhancing NMR Prediction for Organic Compounds Using Molecular Dynamics.”   Kwan, E.E.*; Liu, R.Y.   J. Chem. Theor. Comput.  2015, 11, 5083–5089.  doi: 10.1021/acs.jctc.5b00856; U.S. provisional patent no. 62/220,340.

11. “A Computer Search for Planar Substitution Tilings with n-Fold Rotational Symmetry.”   Gähler, F.; Kwan, E.E.; Maloney, G.R.*   Discrete Comput. Geom.  2015, 53, 445–465.  doi: 10.1007/s00454-014-9659-5.

10. “The Stereochemical Course of Intramolecular Michael reactions.”   Kwan, E.E.; Scheerer, J.R.; Evans, D.A.*   J. Org. Chem.  2013, 78, 175–203.  doi: 10.1021/jo302138z.

9. “Entropic Intermediates and Hidden Rate-Limiting Steps in Seemingly Concerted Cycloadditions. Observation, Prediction, and Origin of an Isotope Effect on Recrossing.”   Gonzalez–James, O.M.; Kwan, E.E.; Singleton, D.A.*   J. Am. Chem. Soc.  2012, 134, 1914–1917.  doi: 10.1021/ja208779k.

8. “Progress Towards the Syntheses of (+)-GB 13, (+)-Himgaline, and Himandridine. New Insights into Intramolecular Imine/Enamine Aldol Cyclizations.”   Evans, D.A.*; Adams, D.J.; Kwan, E.E.   J. Am. Chem. Soc.  2012, 134, 8162–8170.  doi: 10.1021/ja3001776.

7. “ACD/Spectrus Processor Review.”   Kwan, E.E.*   J. Chem. Inf. Model.  2012, 52, 1898–1900.  doi: 10.1021/ci300249w (software review).

6. “Intermolecular Michael Reactions: A Computational Investigation.”   Kwan, E.E.*; Evans, D.A.   Org. Lett.  2010, 12, 5124–5127.  doi: 10.1021/ol102017v.

5. “Lithol Red Salts: Characterization and Deterioriation.”   Stenger, J.*; Kwan, E.E.; Eremin, K.; Speakman, S.; Kirby, D.; Stewart, H.; Huang, S.G.; Kennedy, A.R.; Newman, R.; Khandekar, N.   ePreservation Science  2010, 7, 147–157.  

4. “Structural Elucidation with NMR Spectroscopy: Practical Strategies for Organic Chemists.”   Kwan, E.E.*; Huang, S.G.   Eur. J. Org. Chem.  2008, 2671–2688.  doi: 10.1002/ejoc.200700966.

3. “The Rate of Proton Transfer”   Kwan, E.E.*   J. Chem. Ed.  2007, 12, 5124–5127.  doi: 10.1021/ed084p39 (letter to the editor).

2. “Factors Affecting the Relative Efficiency of General Acid Catalysis.”   Kwan, E.E.*   J. Chem. Ed.  2005, 82, 1026–1030.  doi: 10.1021/ed082p1026.

1. “Competitive Transport and Percolation in Disordered Arrays of Molecularly-Linked Au Nanoparticles.”   Trudeau, P.-E.; Orozco, A.; Kwan, E.E.; Dhirani, A.-A.*  J. Chem. Phys.  2002, 117, 3978–3981.  doi: 10.1063/1.1495838.

Chem 106: Advanced Organic Chemistry


These notes are from a previous iteration of Chem 106.

Course Notes

These course notes are a reinterpretation of the Chem 206 course notes by Professor David A. Evans. If you would like to use them, please contact me. I can provide the component ChemDraw files on request.

Course Outline course organization, assessment, topics, and schedule Energy and Reactivity free energy surface, Hammond postulate, Curtin–Hammett principle, Mayr scales, reactivity-selectivity
Bonding multielectron atoms, LCAO method, natural bond orbitals, resonance, anomeric effect, Bent's rule Pericyclic Reactions π-bonding, aromaticity, Dewar–Zimmerman, electrocyclizations, cycloadditions, sigmatropic shifts
Acyclic Conformational Analysis gauche and syn-pentane interactions, olefins, allylic strain, Thorpe–Ingold Acyclic Stereocontrol hydroboration, directed reactions, epoxidation, Burgi–Dunitz, Cram chelate, Felkin–Anh–Eisenstein
Aldol Reaction Zimmerman–Traxler, enolate and aldehyde facial selectivity, double stereodifferentiating reactions Small Ring Conformational Analysis types of strain, A values, Furst-Plattner, fused systems, oxocarbenium ions
Computational Chemistry I potential energy surface, optimization, basis sets, single point energies, accuracy Computational Chemistry II computed KIEs, Singleton method, distinguishing between mechanisms, solvation
Nucleophilic Substitution endocyclic restriction, Baldwin's rules, ion pairing, SN1 vs SN2 Introduction to NMR chemical shifts, J-coupling, Karplus relation, Hoye's method, nuclear Overhauser Effect
Coupling Constant Practice second-order coupling patterns (courtesy Prof. Andy Phillips), Hoye's method practice Fluorine Couplings in Carbon-13 Spectra size of couplings, practice problems
2D NMR Methods COSY/TOCSY, HSQC vs. HMQC, HMBC, phase-cycling vs. gradients, linear prediction 2D NMR Problem Solving structural elucidation strategies, tabulating data, sample problems
NMR Practice: 2D Problems 1D and 2D spectra NMR Practice: Naringenin 1D and 2D spectra
NMR: Relative and Configuration acetonides, NOE/ROE, homonuclear decoupling, J-based methods, Mosher-type analysis, DFT strategies 2D NMR Solutions detailed solutions to 2D NMR problems
Acidity measurement, gas vs. solution phase, hybridization, induction vs. resonance, solvation effects Organolithium Aggregates aggregates, enthalpy vs. entropy, HMPA and TMEDA, continuous variation, kinetics, optimizing reactions
Tetrahedral Intermediates ester and acetal hydrolysis, linear free energy, direct observation, Weinreb amides Hydrogen Bonding donor-acceptor vs. electrostatic views, optimal geometry, charge and resonance asssistance, cooperativity
π-π Stacking and Cation-π Interactions optimal geometries, electrostatics and dispersion, Hunter–Sanders/Houk–Wheeler models, catalysis N-heterocyclic carbenes bonding, Wanzlick equilibrium, benzoin reaction, Stetter reaction, asymmetric catalysis
Amine Organocatalysis iminium catalysis, enamine catalysis, List–Houk model, kinetics First-Order Kinetics rate laws, approach to equilibrium, two-step system, Michaelis–Menten system, "1+rate" laws
Applications of Kinetics Halpern–Landis hydrogenation, reaction progress kinetic analysis, same vs. different excess Rate Laws elementary reactions, differential vs. integral methods, two-step system, catalytic rate laws
Linear Free Energy Relationships Hammett equation, curvature, alternative references, Taft/Charton/Sterimol parameters, 2D LFERs Kinetic Isotope Effects zero-point energy, hybridization, geometry, Hammond postulate, tunnelling, heavy atom effects
Aldol Reactions Cheat Sheet the key diastereoselective reactions and their transition structures Conformational Analysis of Macrocycles medium and large rings, peripheral attack, transannular reactions
Competitive Kinetic Isotope Effects absolute rates vs. competition, inter- vs. intramolecular KIEs, competition equations Rates and Temperature Arrehnius vs. Eyring, data analysis, interpretation of enthalpy and entropy

Other Course Notes

These course notes have been used in the past for Chem 117 (NMR spectroscopy). If you would like to use them, please contact me. I can provide the component ChemDraw files on request.

Chem 117 Course Outline course organization, assessment, topics, and schedule Introduction to NMR 1D spectra, chemical shift, integration, coupling, magnetic and chemical equivalence
The Chemical Shift diamagnetic effects, carbon chemical shifts, spin-orbit coupling, hydrogen bonding The Coupling Constant energy diagrams, size of couplings, positive vs. negative values, second-order effects
1D NMR Techniques heteronuclear NMR, isotope effects, NOE, vector model, relaxation, inversion recovery, CPMG Data Acquisition and Processing sample preparation, pulse-acquire, Ernst angle, quadrature, ADC and dynamic range, Nyquist theorem
Polarization Transfer quantitative integration, selective population transfer, INEPT/DEPT, spectral editing/APT Computational Methods the PES, conformational searching, molecular mechanics, DFT methods, optimization
Chemical Exchange exchange regimes, selective inversion, saturation transfer, spin-locking, Bloch equations The Nuclear Overhauser Effect transverse vs. longitudinal relaxation, mechanisms for relaxation, transient vs. steady state, NOE vs ROE
Experimental Methods kinetics, no-D NMR, titration, composite and adibatic pulses, composite pulse decoupling Introduction to Product Operators operators for one and two spins, effect of pulses, in- vs. out of phase terms, J-modulation, coherence transfer
Product Operators: Homonuclear Correlation coherence order, multiple quantum coherence, phase modulation and lineshape, COSY/DQF-COSY Product Operators: Heteronuclear Correlation HSQC, HMQC, HMBC, TOCSY, frequency discrimination, P- vs. N-type selection, SHR vs. TPPI/Redfield
Coherence Selection coherence order, transfer pathways, CTP selection, phase cycling with CYCLOPS Pulsed Field Gradients PFGs vs. phase cycling, phase errors, gradient-selection schemes, zero quantum supression
Caveman Guide to NMR Experiments courtesy of Dr. Brian Sparling Spectral Reference Guide frequently used spectral reference tables
Structural Elucidation Review how to determine the structures of natural products using 1D and 2D NMR (Kwan) Optimal 2D NMR Parameters best experiments and parameters for natural products NMR (Reynolds and Enriquez)
Solvent Residual Signals residual solvent NMR signals Solvent Residual Signals (SI) additional data
Organolithium Titration how to titrate organolithium reagents Hoye's Method how to extract first-order couplings from NMR spectra

These course notes have been used in the past for Chem 135 (experimental organic chemistry). If you would like to use them, please contact me. I thank Dr. Andreas Roetheli for helping me to develop these laboratory procedures.

Chem 135 Course Outline course organization, assessment, topics, and schedule Spectroscopy Primer introduction to UV-vis, IR, NMR, and mass spectrometry
Experiment 1: 9-BBN synthesis of 9-BBN and hydroboration of 1-decene Experiment 2: Cross-Coupling preparation of Buchwald pre-catalyst and Suzuki cross-coupling
Experiment 3: Auxiliary Alkylation Myers pseudoephenamine alkylation and cleavage Experiment 4: Dess–Martin Periodinane preparation of DMP and Horner–Wadsworth–Emmons olefination

Computational Chemistry Exercises

This is a series of tutorials designed to cover the basics of performing routine calculations in Gaussian.
The instructions are tailored for the Odyssey Cluster at Harvard University, but will mostly work for Gaussian in general.

Exercise 0:

Odyssey Setup

accessing Odyssey, basic shell commands, transfering files, GaussView, vim Exercise 1:

Conformers of Pentane

drawing structures, running Gaussian jobs, extracting energies, thermochemistry
Exercise 2:

Transition State for an SN2 Reaction

scanning bond lengths, minimum energy path, calculating barriers, solvation Exercise 3:

Choosing the Right Method: Benzene Dimer

single point energies, introduction to scripting, dispersion, counterpoise corrections
Exercise 4:

Selectivity in a Diels-Alder Reaction

finding diastereomeric transition states, composite level single points, selectivity Exercise 5:

Conformational Analysis of Thiourea Catalysts

rapid optimization, conformational analysis with dispersion
Exercise 6:

Water Dimer: Complete Basis Set Extrapolation

complete basis set extrapolation, additivity of energy corrections Exercise 7:

Molecular Properties

making pictures with CYLview, molecular orbitals, electrostatic potentials, point charges