Asymmetric Cascade Aza-Henry/Lactamization Reaction in the Highly Enantioselective Organocatalytic Synthesis of 3‑(Nitromethyl)isoindolin-1-ones from α‑Amido Sulfones

The asymmetric synthesis of novel 3-substituted isoindolinones is herein reported. A new cascade reaction was developed that consisted of the asymmetric nitro-Mannich reaction of suitable α-amido sulfones designed from 2-formyl benzoates, followed by the in situ cyclization of the adducts. Very high...

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Bibliographic Details
Published in:Journal of organic chemistry 2022-07, Vol.87 (13), p.8420-8428
Main Authors: Serusi, Lorenzo, Palombi, Laura, Pierri, Giovanni, Mola, Antonia Di, Massa, Antonio
Format: Article
Language:English
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Summary:The asymmetric synthesis of novel 3-substituted isoindolinones is herein reported. A new cascade reaction was developed that consisted of the asymmetric nitro-Mannich reaction of suitable α-amido sulfones designed from 2-formyl benzoates, followed by the in situ cyclization of the adducts. Very high enantioselectivities, up to 98% ee, and very good yields were obtained in the presence of the readily available neutral bifunctional organocatalyst derived from trans-1,2-diaminocyclohexane, which is known as Takemoto’s catalyst. The investigation of the reactivity of the obtained products allowed either the selective Boc-deprotection or reduction of the nitro group, leading to further functionalized 3-substituted isoindolinones without affecting the enantiomeric purity.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.2c00518