Elizabeth H. Krenske

L-Altruronic acid-based glycoconjugates demonstrate excellent preliminary efficacy as antigens for Enterococcus faecium vaccine development; however, progress has been limited by the poor accessibility of l-altruronic acid. We report here on a concise preparation of a donor-functionalized derivative of l-altruronic acid via a fluorine-directed C-5 epimerization. DFT calculations also reveal how the stereoselectivity of epimerization is influenced by stabilizing effects in the intermediate carbohydrate radicals.

Computational studies reveal how the enzyme responsible for biological methane formation achieves a low-energy transition state by swapping the distal water ligand for a glutamine.

Variable‐temperature NMR spectra of the ten‐membered lactone (–)‐nonenolide reveal that the molecule undergoes a hindered conformational interconversion process, which appears to be characteristic of this class of natural products. Using a combination of quantum mechanics (QM) calculations and molecular dynamics (MD) simulations, we show that the hindered rate process involves a ‘jump‐rope rotation’ that reorients the endocyclic alkene moiety with respect to the rest of the ring. Quantum mechanical calculations provide reasonably accurate predictions of the interconverting species’ chemical shifts, but several discrepancies exist, which we trace to inadequacies in the description of conformer energies in solution. Closer agreement is obtained from an MD‐based analysis of the conformer populations in explicit solvent. This study illustrates some important ways in which solvent effects can influence the accuracy of theoretical chemical shift predictions.

Methylenated cycloheptanoids are synthesized by formal (4+3) cycloadditions of dienes with epoxy allylsilanes as dienophiles in the presence of catalytic amounts of TESOTf. Intermolecular and intramolecular (4+3) cycloadditions with dienes including furans, cyclopentadiene, pyrroles, thiophenes, and benzenes proceeded to provide polycyclic adducts in moderate to good yields.

Larger cage hydrocarbon induced hyperconjugation lowers the energy barrier for resist deprotection ( i.e. , solubility switching), eliminating the need for PFAS-containing PAGs for photoresist design.

A new mechanism for the Stoltz–Grubbs (KO ^t Bu/Et ₃ SiH) silylation of heteroarenes is reported that successfully resolves the important unexplained experimental features of the reaction. The mechanism combines hydride transfer, hydrogen atom transfer (HAT), and single electron transfer (SET) steps (with the substrate hydride adduct being identified as a new SET donor) and is supported by extensive theoretical calculations. Previously proposed heterolytic and radical mechanisms do not involve SET. The discovery of a mechanistic role for SET explains why the silylation reaction simultaneously displays both heterolytic and radical character, and why it does not require free silyl radicals. Previously unexplained experimental results from reactions of isotopically labelled reactants and on the inhibitory effects of electron‐accepting additives can also be understood based on the SET mechanism.

A new mechanism for the Stoltz–Grubbs (KO ^t Bu/Et ₃ SiH) silylation of heteroarenes is reported that successfully resolves the important unexplained experimental features of the reaction. The mechanism combines hydride transfer, hydrogen atom transfer (HAT), and single electron transfer (SET) steps (with the substrate hydride adduct being identified as a new SET donor) and is supported by extensive theoretical calculations. Previously proposed heterolytic and radical mechanisms do not involve SET. The discovery of a mechanistic role for SET explains why the silylation reaction simultaneously displays both heterolytic and radical character, and why it does not require free silyl radicals. Previously unexplained experimental results from reactions of isotopically labelled reactants and on the inhibitory effects of electron‐accepting additives can also be understood based on the SET mechanism.

We present an asymmetric formal total synthesis of pseudolaric acid B (PAB), based on the intramolecular (4+3) cycloaddition of a new class of epoxy enolsilane substrates. This substrate type has the epoxide geminally‐substituted on the tether to the furan, which reacts to yield the trans ‐fused perhydroazulene core of PAB containing the quaternary stereocenter. The reaction is highly diastereoselective, as opposed to cycloadditions of previous substrate types that generate the perhydroazulene framework. The role of the geminal tether in controlling the transition state conformation and the exo ‐selectivity is revealed by density functional theory calculations. Using this intramolecular cycloaddition as the key reaction, together with several one‐pot sequences, a key intermediate in Trost's synthesis of PAB was accomplished, representing the shortest asymmetric synthesis of this anti‐tumor natural product thus far.