ИСТИНА

Recent studies in chemistry of indole and its derivatives are focused on development of robust, effective and convenient chemical technology for the synthesis of natural products and their analogs. These compounds can be powerful tools for impacting biology and medicine. One of the urgent directions in synthetic chemistry is the creating of new pathways leading to substances possessing 4,5,6,7-tetrahydro-1H-indole scaffold. This structural motif is present in two members of Stemona alkaloid family1 making this ring privileged for library design and drug discovery. Moreover, tetrahydroindole derivatives display a wide spectrum of biological activity such as anti-implantation, hypoglycemic, anti-inflammatory and analgesic, potent neuroleptic (e.g. molindone), anti-tumor, etc. On the other hand, tetrahydroindoles are valuable intermediates applied in the synthesis of natural alkaloids such as goniomitine, arcyriacyanin A, 6,7-secoagroclavine, chuangxinmycin, synthetic drugs like pindolol and highly functionalised indoles. Palladium-mediated cyclization of amino propargylic alcohols to pyrroles had been initially disclosed by Utimoto2 et al. In our previous work we have accomplished synthesis of various tetrahydroindoles featuring this methodology3. In our present work we have developed one-pot sequence based on Sonogashira cross-coupling/Pd-mediated 5-endo-dig cyclization and applied this methodology for the gram-scale synthesis of 2-aryl-4,5,6,7-tetrahydroindoles (5 examples). We have estimated that reaction conditions tolerate a wide range of functional groups including nitro and amino moieties. The yield of requisite tetrahydroindoles substantially depends on substituents in aromatic ring and at nitrogen atom. References: 1) Pilli, R.A.; Rosso, G.B.; Ferreira de Oliveira, M.d.C. Nat. Prod. Rep. 2010, 27, 1908. 2) Utimoto, K.; Miwa, H.; Nozaki, H. Tetrahedron Lett. 1981, 22, 4277. 3) Andreev, I.A.; Ryzhkov, I.O., Kurkin, A.V., Yurovskaya M.A. Khim. Geterotsikl. Soedin., 2012, 5 (539), 769.