Regioselection in the synthesis of 4-benzyltetral-1-ones and the new 4-arylbenzosuber-1-ones

The intramolecular Friedel-Crafts acylation of 4,5-diarylpentanoic acids has the possibility to cyclise to either a 6-membered ring to give 4-benzyltetral-1-one or a 7-membered ring to give 4-arylbenzosuber-1-one. Of these, only the former compound class has previously been reported. The impact of the substituents positioning on the outcome of the cyclisation has been investigated. The complete formation of either the tetralone or the benzosuberone regioisomer was possible under the same reaction conditions, dependent upon the ring activation and/or deactivation of the chosen substituents. Selected bromo or methoxy substituents could be used as auxiliaries, included in precursors to afford the desired regioisomer and then subsequently removed. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

The intramolecular Friedel-Crafts acylation of 4,5-diarylpentanoic acids can lead to the formation of either 4-benzyltetral-1-one or 4-arylbenzosuber-1-one. The positioning of the substituents on the aromatic rings has been found to significantly impact the outcome of the cyclisation reaction. By using selected bromo or methoxy substituents as auxiliaries, it is possible to control the formation of the desired regioisomer.