Enhanced Reactivity for Aromatic Bromination via Halogen Bonding with Lactic Acid Derivatives

We report a new method for regioselective aromatic bromination using lactic acid derivatives as halogen bond acceptors with N-bromosuccinimide (NBS). Several structural analogues of lactic acid affect the efficiency of aromatic brominations, presumably via Lewis acid/base halogen-bonding interaction...

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Bibliographic Details
Published in:Journal of organic chemistry 2022-07, Vol.87 (13), p.8492-8502
Main Authors: Baker, Sarah I., Yaghoubi, Mahshid, Bidwell, Samantha L., Pierce, Savannah L., Hratchian, Hrant P., Baxter, Ryan D.
Format: Article
Language:English
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Summary:We report a new method for regioselective aromatic bromination using lactic acid derivatives as halogen bond acceptors with N-bromosuccinimide (NBS). Several structural analogues of lactic acid affect the efficiency of aromatic brominations, presumably via Lewis acid/base halogen-bonding interactions. Rate comparisons of aromatic brominations demonstrate the reactivity enhancement available via catalytic additives capable of halogen bonding. Computational results demonstrate that Lewis basic additives interact with NBS to increase the electropositive character of bromine prior to electrophilic transfer. An optimized procedure using catalytic mandelic acid under aqueous conditions at room temperature was developed to promote aromatic bromination on a variety of arene substrates with complete regioselectivity.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.2c00611