A Silica‐Supported Catalyst Containing 9‐Amino‐9‐deoxy‐9‐epi‐quinine and a Benzoic Acid Derivative for Stereoselective Batch and Flow Heterogeneous Reactions

A heterogeneous, silica‐based catalyst containing 9‐amino‐9‐deoxy‐epi‐quinine (or quinidine) and a derivative of benzoic acid was synthesized through radical thiol‐ene click reaction. The acid component allows the in situ activation of cinchona amino group, acting as a bifunctional catalyst. The het...

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Bibliographic Details
Published in:European journal of organic chemistry 2019-03, Vol.2019 (10), p.2020-2028
Main Authors: Ciogli, Alessia, Capitani, Donatella, Di Iorio, Nicola, Crotti, Simone, Bencivenni, Giorgio, Donzello, Maria Pia, Villani, Claudio
Format: Article
Language:English
Subjects:
Acids
Aminocatalysis
Asymmetric catalysis
Benzoic acid
Catalysis
Catalysts
Chemical reactions
Chemical synthesis
Continuous flow
Cyclohexanone
Enantiomers
Flow velocity
Heterogeneous reactions
Ketones
Organic chemistry
Silicon dioxide
Stereoselectivity
Supported catalysts
Warfarin
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Summary:A heterogeneous, silica‐based catalyst containing 9‐amino‐9‐deoxy‐epi‐quinine (or quinidine) and a derivative of benzoic acid was synthesized through radical thiol‐ene click reaction. The acid component allows the in situ activation of cinchona amino group, acting as a bifunctional catalyst. The heterogenized catalysts efficiently promoted the reaction of ketones with trans‐β‐nitrostyrene, with diastereo‐ and enantioselectivity comparable to those of the homogeneous counterparts (dr up to 90:10 and 90 % ee). In addition, the catalyst retained a constant activity for at least four cycles. Finally, the supported catalyst (9‐amino‐9‐deoxy‐epi‐quinine/achiral acid) was employed under continuous‐flow conditions. Two enantioselective Michael reactions were in sequence performed with the same homemade packed‐bed reactor. The addition of cyclohexanone to trans‐β‐nitrostyrene provided the evaluation of optimal residence time with high level of stereoselection (2 µL/min flow rate, 83 % ee). Furthermore, the flow reactor well performed in the preparation of warfarin (isolated yield 95 %, 78 % ee. in 16 h at room temperature). The dual (chiral amine/achiral acid) solid supported system, making an even easier work‐out, represents a valuable tool for green chemistry and is attractive for large scale applications. A silica‐supported catalyst containing both chiral primary amine cinchona alkaloid and its achiral acid co‐catalyst has been developed. The in situ activated acid/basic catalyst promoted the addition of cyclic ketones to trans‐β‐nitro‐styrene with high stereocontrol. Additionally, the versatility of catalytic machine was attested in continuous‐flow conditions.
ISSN:1434-193X
1099-0690
DOI:10.1002/ejoc.201900148