Energy Read-out as a Probe of Kinetically Hidden Transition States

Abstract

The initial energy in a reactive intermediate is derived from the transition state before the intermediate but can affect selectivity after the intermediate. In this way an observable selectivity can report on a prior, kinetically hidden mechanistic step. This new type of mechanistic probe is demonstrated here for the oxidation of 1-methylcyclobutanol by phthaloyl peroxide/Bu4N+Br–, and it supports a hypobromite chain mechanism in place of the previously proposed hydrogen atom transfer mechanism.

Heavy-Atom Kinetic Isotope Effects: Primary Interest or Zero Point?

“…In this scenario, the nascent reactant will initially have excess thermal energy, which may or may not be dissipated to the solvent before any onward reaction. If the reactant fails to undergo full thermal equilibration , before reacting, the B-M computed KIEs will be incorrect: the reactant will be “hot” as it passes through the TS . The extent of the error depends upon the time scales of intramolecular vibrational energy redistribution (IVR) and thermal transfer to the solvent (intermolecular energy transfer; IET), which are usually an order of magnitude or more faster than diffusion .…”

“…Reference ( F T = 0 or 1.00) and reaction samples should be analyzed back-to-back and identically, using the same NMR instrument, concentrations, solvent source, and acquisition and processing parameters . Strict adherence to the Singleton methodology is essential. ,,,, In recent years, more-sophisticated pulse sequences have been employed to enhance S/N and KIE precision. For example, 1 H-detected 2D [ 13 C, 1 H]-HSQC and DEPT can be used to measure 12 C/ 13 C ratios at natural abundance for hydrogen-bearing carbons (R n C–H), and multiple quantum-filtered (MQF) 19 F­{ 1 H} NMR can be used to measure 12,13 k C KIEs for carbons directly bonded to fluorine (R n C–F)…”

“…The ground-breaking developments outlined above mean that, handled appropriately, heavy-atom KIEs can now be used , to probe transition-state structures, to assess chronology in complex multi-step reactions, or to reveal the behavior of highly reactive intermediates in solution, for which many classical assumptions of chemical kinetics begin to break down. − Heavy-atom KIEs also serve as valuable benchmarks for computational studies of chemical reactivity, which are growing ever more prevalent and, for better or worse, increasingly detached from experimental data . Heavy-atom KIEs are both directly observable and readily calculable, and they benefit from a greater degree of systematic error cancellation than perhaps any other selectivity calculationvaluable assets not simply for interrogating mechanisms but also for appraising computational methodologies against real-world data …”

“…Aims and Scope: Over the past three decades, − ,− , there has been a growth and diversification of the use of heavy-atom KIEs in organic chemistry . However, the unique insights provided by such analyses are perhaps not yet as widely appreciated and applied as they could be.…”

Electrophotochemical Ring-Opening Bromination of tert-Cycloalkanols

“…On the basis of the experimental results and literature reports, a plausible mechanism for the electrophotochemical ring-opening bromination is described in Scheme . At first, the bromide ion would be oxidized on an anode to afford the bromo cation species.…”