Short Approach to Pyrrolopyrazino-, Pyrrolodiazepino-Isoindoles and their Benzo Analogues via the IMDAF Reaction

Author(s): Fedor I. Zubkov*, Daria N. Orlova, Vladimir P. Zaytsev, Alexander A. Voronov, Eugeniya V. Nikitina, Victor N. Khrustalev, Roman A. Novikov, Mikhail Krasavin, Alexey V. Varlamov

Journal Name: Current Organic Synthesis

Volume 14 , Issue 5 , 2017

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Aim and Objective: A new approach to synthesis of isoindoles condensed with other heterocycles and revelation of their spatial structure for biochemistry purposes was the main objective of this research.

Material and Method: Starting materials for the proposed method, 1-furyl substituted pyrrolo[1,2-a]pyrazines, pyrrolo[1,2-a][1,4]diazepines and their benzoannulated analogues - 4-furyl substituted pyrrolo[1,2-a]quinoxalines and pyrrolo[1,2-a][1,4]benzodiazepines, were synthesized by known procedures. These compounds, all containing a furfurylamine moiety, were introduced into the tandem acylation/ intramolecular furan Diels-Alder (IMDAF) reaction with α,β-unsaturated acid anhydrides (maleic and itraconic anhydrides). In most cases, the key step – the IMDAF reaction – proceeds diastereospecifically with simultaneous formation of five new stereogenic centers and affording the title compounds in mild conditions with satisfactory overall yields.

Results: Consequently a broad series of 10,12a-epoxypyrrolo[2’,1’:3,4]pyrazino[2,1-a]isoindoles, 11,13a-epoxypyrrolo[ 2’,1’:3,4][1,4]diazepino[2,1-a]isoindoles, tetrahydro-14bH-12,14a-epoxyisoindolo[2,1-a]pyrrolo[2,1-c]quinoxalines, and tetrahydro-9H,15bH-13,15a-epoxyisoindolo[1,2-c]pyrrolo[1,2-a][1,4]benzodiazepines was synthesized and their space structure was elucidated by X-ray analysis.

Conclusion: New effective method for synthesis of isoindoles condensed with various heterocycles was proposed. The method is based on the IMDAF reaction and provided a broad diversity of target molecules with controlled stereochemistry.

Keywords: Furans, Diels-Alder reaction, cycloaddition, domino reaction, pyrrolopyrazine, pyrrolodiazepine, IMDAF reaction.

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Article Details

Year: 2017
Page: [733 - 746]
Pages: 14
DOI: 10.2174/1570179414666161116123221
Price: $65

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