from first principles PP-I-1

PP-III-49An Efficient Nenitzescu Indole Synthesis in the Presence of Lewis AcidCatalystsKlychnikov M.K., Kornienko A.G., Velezheva V.S.A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences,Moscow, Russiachemkli@yandex.ruOOCOR 2HOR 2 CH 2 Cl 2CH+3NHNCH 3Catalyst*R 1O R 1 1 2,3NQ or PBQNQ –1,4- naphthoquinonePBQ – 1,4-benzoquinoneR 1 : Bn, Bu, allyl, Ph, C 6 H 4 -4-Cl, C 6 H 4 -4-COOMe, C 6 H 4 -3-COOMe, C 6 H 4 -4-CH 3 , C 6 H 4 -3-CH 3 ,C 6 H 4 -2-CH 3 , C 6 H 4 -4-OMe, C 6 H 3 -3,4-di-Cl, C 6 H 3 -3-NO 2 -4-Me,R 2 : OEt, Me, Ph* Catalyst : ZnI 2 , ZnCl 2 , InCl 3 – 60-85% yield of 2,3;Cu(OTf) 2 , CuCl, CuI, Hg(OAc) 2 , CAN –17-32% yield of 2,3AlCl 3 –65% yield of 2Scheme 1The Nenitzescu indole synthesis is a chemical reaction that produces the medicinally relevanthighly functionalized 5-hydroxyindoles and 5-hydroxybenzo[g]indoles from substitutedenaminoesters or enaminoketones 1 and 1,4-benzoquinone or 1,4-naphthoquinone under nonredoxLewis acids catalyzed very mild conditions[1]. However, the yields and selectivities arestrongly dependent on the metal salt (Lewis acids) employed. Competing oxidativetransformations of intermediates are typical for the classical redox conditions (in polar solventswithout application of a catalyst). We studied which type of simple Lewis acids (from “oxophilic”to “azaphilic”) (Scheme 1) can be better than ZnCI 2 or ZnI 2 employed by us and others in nonredoxmodification of the Nenitzescu reaction [1]. The weak and hard oxophilic Lewis acids wereshown to afford the indoles in low yields. The azaphilic CAN and Cu salts proved to be unsuitableas catalysts for the indole synthesis probably due to their oxidative properties. The best yields(60-85%) of indoles 2, 3 were gained when the process was conducted in the presence of catalystswith moderate Lewis acidity and oxophilicity, such as ZnCI 2 , ZnI 2 or InCl 3 [2]. Thus, thereaction pathway is dependent on the Lewis acid catalyst applied.References:[1] V. Velezheva, A. Kornienko , S.Topilin, A. Turashev , A.Peregudov, P. Brennan. J. Heterocycl.Chem. 2006, 43, 101-107[2] S. Kobayashi, T. Busujima, S. Nagayama, Chem. Eur. J. 2000, 6, 3491-3494202