Experimental and Theoretical Investigation of the Synchronicity of Ambident Silyloxypyrone-Based (5 + 2) Cycloadditions

Abstract

The reaction pathway of silyloxypyrone-based (5 + 2) cycloadditions was determined to be extremely dependent on the nature of the dipolarophile. Neutral alkenes were the least reactive, whereas both electron-deficient and electron-rich dipolarophiles were more reactive, thus providing evidence for ambident oxidopyrylium intermediates. Qualitative rate studies, Hammett linear free energy relationships, and theoretical calculations combined to provide evidence for a spectrum of reactivity that passes through the borderlands of concerted and stepwise.

Net Intermolecular Silyloxypyrone-Based (5+2) Cycloadditions Utilizing Amides as Enabling and Cleavable Tethers

“…Even more striking was the fact that tert -butyl amide 1t gave complete conversion in <5 h because the yield of 2t includes acylation of the amine (Scheme , eq 2). In fact, conversion to adduct 2t was observed at 0 °C . Comparison to the intramolecular Diels–Alder cycloaddition is quite informative.…”

“…A detailed computational study was undertaken to investigate these amide-tethered cycloadditions in comparison to previous carbon-tethered variants. , Initial conformational searches were carried out using CREST, and subsequent DFT calculations were carried out with Gaussian16 . The M06-2X functional with D3(0) dispersion correction was used to locate stationary points, because this functional is known to perform well for main group thermochemistry and kinetic studies .…”

“…In fact, conversion to adduct 2t was observed at 0 °C. 9 Comparison to the intramolecular Diels−Alder cycloaddition is quite informative. Whereas tert-butyl acrylamides tethered to furans afforded cycloadducts spontaneously upon acylation at room temperature, 10 examples of less hindered amides in similar systems required refluxing to achieve cycloaddition.…”