Course Notes

Subject	Description
Advanced Organic Chemistry	bonding, organic reactions, reactivity
Computational Chemistry	tutorials on how to use Gaussian
NMR Spectroscopy	1D and 2D methods, coupling constants, stereochemistry, pulse sequences
Experimental Organic Chemistry	lab procedures for advanced undergraduates

Advanced Organic Chemistry

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

• 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

• Aldol Reactions Cheat Sheet
  the key diastereoselective reactions and their transition structures

• Small Ring Conformational Analysis
  types of strain, A values, Furst-Plattner, fused systems, oxocarbenium ions

• Conformational Analysis of Macrocycles
  medium and large rings, peripheral attack, transannular reactions; courtesy of Dr. Joe Wzorek

• 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, S_N1 vs S_N2

• 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

• 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

• Competitive KIEs
  absolute rates vs. competition, inter- vs. intramolecular KIEs, competition equations

• Rates and Temperature
  Arrehnius vs. Eyring, data analysis, interpretation of enthalpy and entropy

Computational Chemistry

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

NMR Spectroscopy

These course notes were previously used to teach Chem 117 at Harvard University.

• 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

• NMR: Relative and Configuration
  acetonides, NOE/ROE, homonuclear decoupling, J-based methods, Mosher-type analysis, DFT strategies

• Coupling Constant Practice
  second-order coupling patterns (courtesy Dr. 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

• 2D NMR Solutions
  detailed solutions to 2D NMR problems

• Caveman Guide to NMR Experiments
  for Varian/Agilent systems; courtesy of Dr. Brian Sparling

• Spectral Reference Guide
  frequently used spectral reference tables; courtesy of Dr. Brian Sparling

Experimental Organic Chemistry

These lab experiments have been used in the past for Chem 135 at Harvard University. If you would like to use them, please contact me. I thank Dr. Andreas Roetheli for helping me to develop these laboratory procedures.

• 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