Asymmetric Synthesis of Chromans Through Bifunctional Enamine‐Metal Lewis Acid Catalysis

Cooperative enamine‐metal Lewis acid catalysis has emerged as a powerful tool to construct carbon‐carbon and carbon‐heteroatom bond forming reactions. A concise synthetic method for asymmetric synthesis of chromans from cyclohexanones and salicylaldehydes has been developed to afford tricyclic chrom...

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Bibliographic Details
Published in:Chemistry : a European journal 2022-05, Vol.28 (27), p.e202200224-n/a
Main Authors: Davis, Jacqkis, Gharaee, Mojgan, Karunaratne, Chamini V., Cortes Vazquez, Jose, Haynes, Mikayla, Luo, Weiwei, Nesterov, Vladimir N., Cundari, Thomas, Wang, Hong
Format: Article
Language:English
Subjects:
Asymmetric synthesis
Asymmetry
bifunctional catalysis
Carbon
Catalysis
Catalysts
Chelation
Chemistry
chromans
Crystallography
Cyclohexanone
enamine catalysis
Enantiomers
Lewis acid
metal Lewis acid catalysis
Metals
Stereoselectivity
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Summary:Cooperative enamine‐metal Lewis acid catalysis has emerged as a powerful tool to construct carbon‐carbon and carbon‐heteroatom bond forming reactions. A concise synthetic method for asymmetric synthesis of chromans from cyclohexanones and salicylaldehydes has been developed to afford tricyclic chromans containing three consecutive stereogenic centers in good yields (up to 87 %) and stereoselectivity (up to 99 % ee and 11 : 1 : 1 dr). This difficult organic transformation was achieved through bifunctional enamine‐metal Lewis acid catalysis. It is believed that the strong activation of the salicylaldehydes through chelating to the metal Lewis acid and the bifunctional nature of the catalyst accounts for the high yields and enantioselectivity of the reaction. The absolute configurations of the chroman products were established through X‐ray crystallography. DFT calculations were conducted to understand the mechanism and stereoselectivity of this reaction. A concise method for the asymmetric synthesis of tricyclic chromans from salicylaldehydes and cyclic ketones was developed through bifunctional enamine‐metal Lewis acid catalysis. Mechanism of the chroman formation reaction was proposed and investigated with deuterium experiments and DFT calculations. Tricyclic chromans containing three consecutive stereogenic centers were prepared in good yields (up to 87 %) and stereoselectivity (up to 99 % ee and 11 : 1 : 1 dr).
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.202200224