Ryan Pemberton

Learn More
Density functional and ab initio methods have been used to study the mechanisms for key dynamic processes of the experimentally known S4-symmetric [16]annulene (1a). Using BH&HLYP/6-311+G** and B3LYP/6-311+G**, we located two viable stepwise pathways with computed energy barriers (Ea = 8-10 kcal/mol) for conformational automerization of 1a, in agreement(More)
Density functional and coupled cluster calculations show that facile thermal configuration change in [12]annulene occurs via a twist-coupled bond-shifting mechanism. The transition state for this process is highly aromatic with Möbius topology. At the CCSD(T)/cc-pVDZ//BH&HLYP/6-311+G** level, the isomerization of tri-trans-[12]annulene 1a (CTCTCT) to its(More)
Although the aromatic aza-Claisen rearrangement is a general strategy for accessing substituted aromatic amines, there are no highly enantioselective examples of this process. We report the first Brønsted acid catalyzed enantioselective indole aza-Claisen rearrangement for the synthesis of chiral 3-amino-2-substituted indoles. We present evidence for an(More)
A biomimetic total synthesis of santalin Y, a structurally complex but racemic natural product, is described. The key step is proposed to be a (3+2) cycloaddition of a benzylstyrene to a "vinylogous oxidopyrylium", which is followed by an intramolecular Friedel-Crafts reaction. This cascade generates the unique oxafenestrane framework of the target molecule(More)
We report density-functional and coupled-cluster calculations on conformation change and degenerate bond shifting in [10]annulene isomers 1-5. At the CCSD(T)/cc-pVDZ//CCSD/6-31G level, conversion of the twist (1) to the heart (2) has a barrier of 10.1 kcal/mol, compared to Ea = 16.2 kcal/mol for degenerate "two-twist" bond shifting in 1. Pseudorotation in(More)
DFT (both B3LYP and M06-2X), CASSCF, and CASPT2 calculations were used to investigate competing [3, 3] and [3, 5] sigmatropic shifts and intramolecular [4+2] cycloaddition of 1,3,7-octatriene. In accord with previous results on 1,5-hexadiene, CASSCF calculations found both stepwise and concerted pathways for the [3, 3] rearrangement. For the competing [3,(More)
Quantum chemical calculations coupled to experiments were used to predict covalent hydration propensities of biologically relevant α-ketoamides. Experimentally determined hydration equilibrium constants for related ketones and aldehydes were compared to computationally determined values to develop a method for predicting hydration equilibrium constants.(More)
Human respiratory syncytial virus (RSV) is a negative-sense RNA virus and a significant cause of respiratory infection in infants and the elderly. No effective vaccines or antiviral therapies are available for the treatment of RSV. ALS-8176 is a first-in-class nucleoside prodrug inhibitor of RSV replication currently under clinical evaluation. ALS-8112, the(More)
The development of the domino reaction between an aminoethyl-substituted diene and maleic anhydride to afford an N-substituted octahydroisoquinolin-1-one is described. A typical procedure involves the treatment of a 1-aminoethyl-substituted butadiene with maleic anhydride at 0 °C to room temperature for 20 min under low-solvent conditions, which affords a(More)