Theoretical Insight into the Reversal of Chemoselectivity in Diels-Alder Reactions of α,β-Unsaturated Aldehydes and Ketones Catalyzed by Brønsted and Lewis Acids

Abstract

Experimentally, a reversal of chemoselectivity has been observed in catalyzed Diels–Alder reactions of α,β-unsaturated aldehydes (e.g., (2E)-but-2-enal) and ketones (e.g., 2-hexen-4-one) with cyclopentadiene. Indeed, using the triflimidic Brønsted acid Tf2NH as catalyst, the reaction gave a Diels–Alder adduct derived from α,β-unsaturated ketone as a major product. On the other hand, the use of tris(pentafluorophenyl)borane B(C6F5)3 bulky Lewis acid as catalyst gave mainly the cycloadduct of α,β-unsaturated aldehyde as a major product. Our aim in the present work is to put in evidence the role of the catalyst in the reversal of the chemoselectivity of the catalyzed Diels–Alder reactions of (2E)-but-2-enal and 2-Hexen-4-one with cyclopentadiene. The calculations were performed at the ωB97XD/6-311G(d,p) level of theory and the solvent effects of dichloromethane were taken into account using the PCM solvation model. The obtained results are in good agreement with experimental outcomes.

On the Question of Stepwise [4+2] Cycloaddition Reactions and Their Stereochemical Aspects

“…These studies were performed in two ways, studying the kinetics of the reaction and monitoring the cycloaddition environment with spectroscopic methods. Both of these techniques confirmed the formation of the zwitterionic intermediate product, which, according to the authors, undergoes competitive cyclisation to the cyclohexene analogue(52) or to the HDA-type adduct(54). Later DFT studies showed that, in fact, the course of this reaction is even more complex[66].…”

“…This is a consequence of the interaction of the ionic liquid cations with the 2-π-component of the analysed reaction [53]. It should be noted that, for analogous reactions involving the less β-deficient 2-π-components, a similar catalytic effect accelerates the cycloaddition but does not promote the stepwise mechanism [54]. The cycloaddition reactions of cyclopentadiene 1 with fumaric acid esters 26 (Scheme 9) have been the subject of detailed studies by many research groups.…”