Taming Keteniminium Reactivity by Steering Reaction Pathways: Computational Predictions and Experimental Validations

Abstract

Keteniminium ions, the nitrogen analogues of ketenes, exhibit high reactivity toward olefins and π-systems. Previous results from the Maulide group demonstrated an unexpected propensity for an alternative intramolecular Bellus− Claisen-type rearrangement rather than an expected intramolecular (2 + 2) cycloaddition. We have conducted a cooperative density functional theory/experimental investigation of this process, seeking insights into the competition between the observed Claisen-type reaction and the historically expected (2 + 2) cyclization. Our calculations revealed a surprisingly small difference in the free energy barrier between these two intramolecular reactions. Further theoretical and experimental investigations probe the electronics of the substrate, rationalize a competing deallylation side reaction, and demonstrate the proof-of-concept for an enantioselective (2 + 2) variant.

Kinetic, Thermodynamic, and Dynamic Control in Normal vs. Cross [2 + 2] Cycloadditions of Ene-Keteniminium Ions: Computational Understanding, Prediction, and Experimental Verification

“…We point out that during our preparation of this manuscript, Maulide and Houk reported their insightful mechanism of the [2 + 2] reaction of ene-keteniminium ions, which was found to be kinetically controlled for their substrates. 7,8 In our study reported here, the intramolecular [2 + 2] reactions of eneketeniminiums, with more examples compared to those in Maulide and Houk's paper, are very complex. We found that the regiochemistry 9 in some cases is kinetically controlled.…”

Axially chiral styrene-based organocatalysts and their application in asymmetric cascade Michael/cyclization reaction

“…In order to reveal the key role of the catalyst in the enantioselectivity control of the cascade Michael/cyclization reaction, we performed density functional theory (DFT) calculations at the M06-2X/6-311++G(d,p) (solvent = DCE, SMD)//M06-2X/6-31G(d,p) (vacuum) level to investigate the reaction pathway 12 (see ESI, Fig. S4 † ).…”

Recent advances in the application of [2 + 2] cycloaddition in the chemical synthesis of cyclobutane-containing natural products

“…Currently, substituted cyclobutane motifs can be synthesized through two main methods in this condition. One is the addition of olefinic substrates to ketene [ 19 , 32 – 40 ] or keteniminium ions [ 41 – 49 ] to produce cyclobutanone, followed by multi-stage functional group transformations. This approach has been proven to be highly effective and reliable.…”