Facile synthesis of pyrrolo[2,1- a ]isoquinolines by domino reaction of 1-aroyl-3,4-dihydroisoquinolines with conjugated
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ORIGINAL ARTICLE
Facile synthesis of pyrrolo[2,1‑a]isoquinolines by domino reaction of 1‑aroyl‑3,4‑dihydroisoquinolines with conjugated ketones, nitroalkenes and nitriles Grigorii S. Astakhov1,2 · Rinat R. Shigaev1 · Tatiana N. Borisova1 · Anastasia A. Ershova1 · Alexander A. Titov1 · Alexey V. Varlamov1 · Leonid G. Voskressensky1 · Maria D. Matveeva1 Received: 9 September 2020 / Accepted: 26 September 2020 © Springer Nature Switzerland AG 2020
Abstract A convenient protocol for the synthesis of 5,6-dihydropyrrolo[2,1-a]isoquinolines with various electron-withdrawing substituents at C-2 atom is described. This approach is based on the two-component domino reaction of 1-aroyl-3,4-dihydroisoquinolines with α,β-unsaturated ketones, nitroalkenes and acrylonitrile. Depending on the selected substrates, the reaction was performed in TFE under reflux or under microwave irradiation. Only for the two examples, a transition metal catalyst was used. Graphic abstract
Keywords Domino reaction · Pyrroloisoquinolines · Unsaturated ketones · Nitriles · Nitroalkenes
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11030-020-10146-7) contains supplementary material, which is available to authorized users. * Maria D. Matveeva [email protected] 1
Department of Organic Chemistry, Peoples’ Friendship, University of Russia (RUDN University), Miklukho‑Maklaya st 6, Moscow, Russia 117198
Laboratory of Metal Hydrides (MHLab), A. N. Nesmeyanov Institute of Organoelement Compounds (INEOS), Russian Academy of Sciences, Vavilov St. 28, GSP‑1, B‑334, Moscow, Russia 119991
2
Pyrrolo[2,1-a]isoquinoline ring represents a key structural fragment of different alkaloids such as Erythrina-type alkaloids or compounds isolated from Carduus crispus L. The alkaloids of the Erythrina L. genus (Fabaceae) belong to the one of the most important series of pyrroloisoquinolines exhibiting various pharmacological properties including hypotensive, sedative, anticonvulsive, curare-like and anti-HIV-1 properties [1–5]. Also, the Erythrina extracts and isolated alkaloids demonstrate anxiolytic properties [6–13]. Moreover, Erythrina alkaloids activate G ABAA receptors [14] and selectively inhibit nicotinic acetylcholine receptors, especially the receptors of α4β2 subtype [6, 15, 16]. The alkaloids Crispine A ( +) and Crispine B isolated from
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Molecular Diversity
pyrrole core [31–36]. Recently, our group has demonstrated the preparation of functionally substituted on the pyrrole ring pyrrolo[2,1-a]isoquinolines based on domino reactions of 3,4-dihydro-1-aroylisoquinolines with electron-deficient alkynes, α,β-unsaturated aldehydes and cross-conjugated vinyl ethynyl ketones [37–40]. Thus, continuing our research of the domino reactions with 3,4-dihydro-1-aroylisoquinolines, we tested conjugated ketones, nitroalkenes and nitriles as substrates. To the best of knowledge, the construction of annulated pyrrole cycle based on the reaction of iminoketone
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