A Facile Anti-selective Synthesis of 3-Nitropyridin-2-ones Using Morita- Baylis Hillman Adduct of Nitroalkene

Author(s): Vijai K. Rai, Ganeshwar P. Sahu, Manorama Singh, Ankita Rai

Journal Name: Letters in Organic Chemistry

Volume 13 , Issue 8 , 2016

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Graphical Abstract:


Background: Amide functionality is an important in many areas of chemistry, including peptide, polymer, and complex molecule synthesis. Furthermore, Morita-Baylis-Hillman (MBH) reaction is well known efficient and economical carbon-carbon bond forming reaction which affords densely functionalized scaffolds. δ-Lactams are important constituents of natural products and have widespread applications from pharmaceuticals to synthetic organic chemistry. To the best of our knowledge, MBH adducts of nitro alkenes and their further oxidized products have not been utilized to construct the target molecule of present investigation. With aim to incorporate nitro group in pyridin-2-ones, we wished to prepare MBH adduct of nitroalkenes, which would be a novel scaffold that can be utilized for synthesis of diverse molecules.

Methods: A flame-dried round bottom flask was charged with benzimidazolium salt, α- nitrocinnamaldehyde, phenacyl bromide, and amine in THF/ButOH under positive pressure of nitrogen followed by addition of DBU. The resulting pale yellow solution was stirred for 12-14 h at room temperature and finally after work-up we isolated the desired amide. Then, a mixture of prepared amide and molecular iodine in dichloromethane was stirred at room temperature for 4.5-6 h yields the target lactams.

Results: [E]-α-Nitrocinnamaldehydes, prepared from Morita-Baylis-Hillman adduct of nitoalkenes, were converted into functionalized amides (81-95%) under the catalysis of N-heterocyclic carbenes. The reaction proceeds via d3 nucleophile of homoenolate and involves three components coupling strategy. A probe to utilized the prepared amide scaffold for construction of pyridin-2-one was also performed and the reactions gave excellent yields (82-93%) of pure products with highly diastereoselective (>92%) in favor of trans isomer.

Conclusion: We have documented an original NHC-catalyzed direct synthesis of α-nitro amides with diverse functionalities, which opens up a new aspect for the utility of MBH adducts of nitroalkenes in organic synthesis. We have also disclosed a new anti-selective synthesis of 3-nitropyridin-2-ones from the prepared amide scaffold. Thus, the envisaged atom-economic strategy for the synthetically important functionalized amides and pharmaceutically important 2-pyridones would be a practical alternative to the existing procedures for their preparations.

Keywords: Nitroalkene, Baylis-Hillman adduct, N-heterocyclic carbene, pyridin-2-one, stereoselectivity.

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Article Details

Year: 2016
Published on: 28 November, 2016
Page: [547 - 553]
Pages: 7
DOI: 10.2174/1570178613666160930122047
Price: $65

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