Tuning Photoenolization-Driven Cycloadditions Using Theory and Spectroscopy

Abstract

The first broad spectrum investigation into the photoenolization/Diels-Alder (PEDA) sequence was carried out using M06-2X/6-31+G(d,p) in conjunction with SMD solvation and supported by experimental UV−vis spectroscopy. A test set of 20 prodienes was chosen to examine the role of the H atom acceptor group (substituted and unsubstituted carbonyl, thiocarbonyl, and imine), the H atom donor group, and bystander ring substituents. As reaction partners for the photogenerated dienes, a diverse test set of 20 dienophiles was examined, comprising electron rich, electron poor, neutral, strain activated, hydrocarbon, and heteroatom-containing molecules including CO 2 and CO. A key finding of this work is the demonstration that the PEDA sequence of carbonyl based prodienes is tolerant of most substitution patterns. Another is that thiocarbonyl derivatives should behave analogously to the carbonyls but are likely to do so much more slowly, due to an inefficient intersystem crossing, an endothermic 1,5-hydrogen atom transfer (HAT) step, and a [1,5] sigmatropic H shift to regenerate the starting material that outcompetes the [4 + 2]cycloaddition. In contrast, the T 1 state of the ortho-alkyl imines displays the incorrect orbital symmetry for 1,5-HAT and is correspondingly accompanied by higher barriers, even in the excited state. However, provided these barriers can be overcome, the remaining steps in the PEDA sequence are predicted to be facile. The Diels−Alder reaction is predicted to be of much broader scope than reported synthetic literature: while electron poor dienophiles are expected to be the most reactive partners, ethylene and electron rich alkenes should react at a synthetically useful rate. CO is predicted to undergo a facile (4 + 1)cheletropic addition instead of the normal [4 + 2]cycloaddition pathway. This unique photoenolization/cheletropic addition (PECA) sequence could provide metal-free access to benzannelated cyclopentanones.

Mechanism of the Aza-Piancatelli Reaction: Scope and Limitations of Furan Substitution in Donor–Acceptor Stenhouse Adduct Synthesis

“…The combination of M06-2X and SMD models has been demonstrated to be accurate for organic reactions in polar solvents. 23 3D structures were prepared using the CYLview 1.0 program. 24…”

“…Solvation was included using the SMD implicit solvation model and THF as a solvent, which is used experimentally in the aza-Piancatelli reaction. The combination of M06-2X and SMD models has been demonstrated to be accurate for organic reactions in polar solvents . 3D structures were prepared using the CYLview 1.0 program…”

Fluorescent and Catalytically Active Single Chain Nanoparticles

“…Photochemically induced [4 + 2] cycloadditions can be achieved by photoenolization of o MBA and subsequent Diels–Alder reaction with electron-deficient dienophiles. Mechanistically, the 1,5-hydrogen atom transfer taking place on the triplet manifold leads to a ( Z )-enol, constituting a highly reactive diene. − When alkynes are used as dienophiles, the initially formed non-fluorescent 1,4-dihydro-1-naphthole cycloadduct can be quantitatively converted to the respective fluorescent naphthalene via E1-elimination in the presence of catalytic amounts of acid.…”

Regioisomerism in Symmetric Dimethyl Dialdehydes Dictates their Photochemical Reactivity

“…A recent study by Coote and co-workers theoretically investigated the role of substituents and dienophiles and found that the reaction is tolerant of most substitutions, critically broadening the potential synthetic toolbox. 27 PEDA reactions where each enolization system can be accessed with a unique wavelength are fascinating enities, opening the door to modify and implement this efficient reaction into complex molecular structures. Indeed, we recently introduced unsymmetric methylisophthalaldehydes (MIAs), which undergo two wavelength-gated PEDA reactions to form heterobifunctional adducts.…”