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Abstract A new empirical electrophilicity reactivity parameter,ERB, was developed based on the rotational barriers of a series ofN‐phenylimide molecular rotors containing various electrophilic groups. In the bond rotation transition state, these electrophilic groups form close contact with an electronegative C═O oxygen. Thus, strong electrophilic groups significantly lowered the rotational barrier. As a result, the rotational barriers were inversely correlated with the strengths of the electrophiles. The rotational barriers were measured by dynamic NMR (EXSY), enabling the quantification across a wide range of types of electrophiles. Computational analysis confirmed that the observed variations arose from intramolecular interactions in the transition state, where the C═O oxygen served as a probe of both the electrophilic group's electrostatic potential and steric accessibility. By simultaneously capturing attractive and repulsive transition state interactions,ERBprovides an effective means of predicting electrophilicity and reactivity trends across a broad range of electrophiles and reaction types. The utility ofERBwas initially validated using a series of rotors containing Michael addition electrophiles, followed by broader application to a diverse array of reactions involvingsp3andsp2electrophiles, including SN2, SNAr, Pd‐oxidative addition, and Sonogashira reactions.
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Through‐Space, Lone‐Pair Promoted Aromatic Substitution: A Relay Mechanism Can Beat Out Direct Activation
Abstract We report a detailed experimental and theoretical analysis of through‐space arene activation with halogens, tetrazoles and achiral esters and amides. Contrary to previously assumed direct activation through σ‐complex stabilization, our results suggest that these reactions proceed by arelaymechanism wherein the lone pair‐containing activators form exothermic π‐complexes with electrophilic nitronium ion before transferring it to the probe ring through low barrier transition states. Noncovalent interactions (NCI) plots and Quantum Theory of Atoms in Molecules (QTAIM) analyses depict favorable interactions between the Lewis base (LB) and the nitronium ion in the precomplexes and the transition states, suggesting directing group participation throughout the mechanism. The regioselectivity of substitution also comports with a relay mechanism. In all, these data pave the way for an alternate platform of electrophilic aromatic substitution (EAS) reactions.
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- Award ID(s):
- 2102116
- PAR ID:
- 10440856
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Chemistry – A European Journal
- Volume:
- 29
- Issue:
- 52
- ISSN:
- 0947-6539
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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