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Updated: Mar 21, 2026

Preparation of a Corannulene-functionalized Hexahelicene by CopperI-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units
Published on: September 18, 2016
Computational Methods to Predict the Regioselectivity of Electrophilic Aromatic Substitution Reactions of
Monika Kruszyk1,2, Mikkel Jessing1, Jesper Langgaard Kristensen2
1Discovery Chemistry and DMPK, Neuroscience Drug Discovery, H. Lundbeck A/S , Ottiliavej 9, 2500 Valby, Denmark.
Abstract:
The validity of calculated NMR shifts to predict the outcome of electrophilic aromatic substitution reactions on different heterocyclic compounds has been examined. Based on an analysis of >130 literature examples, it was found that the lowest predicted (13)C and/or (1)H chemical shift of a heterocycle correlates qualitatively with the regiochemical outcome of halogenation reactions in >80% of the investigated cases. In the remaining cases, the site of electrophilic aromatic substitution can be explained by the calculated HOMO orbitals obtained using density functional theory. Using a combination of these two methods, the accuracy increases to >95%.
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