Synthesis of carbazoles and 1,2-dihydrocarbazoles by domino ‘twofold Heck/6p-electrocyclization’ reactions of di-, tri- and tetrabromoindoles Munawar Hussain a , Serge-Mith  erand Tengho Toguem a , Rasheed Ahmad a, b ,Ðặng Thanh T  ung a , Ingo Knepper a , Alexander Villinger a , Peter Langer a, c, * a Institut f€ ur Chemie, Universit€ at Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany b Department of Petroleum Technology, University of Karachi, University Road, Karachi 75270, Pakistan c Leibniz-Institut f€ ur Katalyse e. V. an der Universit€ at Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany article info Article history: Received 18 March 2011 Received in revised form 3 May 2011 Accepted 5 May 2011 Available online 14 May 2011 Keywords: Carbazoles Catalysis Cyclizations Indoles Heck reaction Palladium abstract Di-, tri- and tetra-alkenylindoles were prepared by palladium(0)-catalyzed Heck cross-coupling reactions of di-, tri- and tetrabromo-N-methylindoles. The reactions were carried out at 90  C using a novel biaryl monophosphine ligand developed by Buchwald and co-workers. 1,2-Dihydrocarbazoles were formed by a domino ‘twofold Heck/6p-electrocyclization’ when the reaction was carried out at higher temperature. The regioselectivity of the Heck reaction of 2,3,6-tribromo-N-methylindoles was in favour of carbon atoms C-2 and C-3. The 1,2-dihydrocarbazoles were transformed, by Pd/C-catalyzed dehydrogenation, into the corresponding carbazoles in high yield. Ó 2011 Elsevier Ltd. All rights reserved. 1. Introduction Carbazole is a natural product isolated for the first time from coal tar in 1872 by Graebe and Glaser. Carbazole derivatives are of significant pharmacological relevance because of their antifungal, antibiotic and antitumour activities. Simple carbazole alkaloids were isolated in the 1960s as natural products from plant sources. Murrayafoline A and murrayaquinone B are examples of naturally occurring carbazoles and carbazolequinones isolated from the root bark of Murraya euchrestifolia Hayata (Fig. 1). 1,2 A number of synthetic approaches to carbazoles have been reported. In recent years, transition metal catalyzed reactions have been extensively used for the synthesis of carbazoles. For example, a general approach to carbazoles relies on iron-mediated cycliza- tion reactions (stoichiometric use of iron complexes). 1d Later, a catalytic approach to carbazoles has been developed, which is based on BuchwaldeHartwig reactions of aryl halides with anilines and subsequent oxidative cyclizations. 3 Carbazoles have been also prepared by palladium-catalyzed cyclization of anilines with 1,2-dihaloalkenes, a domino reactions recently developed by Ackermann and Althammer. 4 Classic syntheses of carbazoles in- clude, for example, DielseAlder reactions of 2- or 3-vinylindoles with various dienophiles. 5 Carbazoles have also been prepared by thermal 6p-electrocyclization reactions of 2,3-di(alkenyl)in- doles. 6,7 The scope of this method was severely limited by the fact that the synthesis of the precursors, 2,3-di(alkenyl)indoles, was complicated and required many steps. Acceptor-substituted 2,3- di(alkenyl)indoles were prepared by Pd(II)-catalyzed reactions of carbon atom C-3 of 2-formylindoles with alkenes to form 2-formyl- 3-vinylindoles. The aldehyde group was subsequently transformed into an alkenyl group by means of a Wittig reaction. Attempts to prepare 2,3-di(alkenyl)indoles by double Wittig reaction of 2,3- diformyl-N-methylindole proved to be unsuccessful, due to the unstable nature of the bis-aldehyde and low yields. N H MeO Me O O N H Me OMe Murrayafoline A Murrayaquinone B Fig. 1. Carbazoles isolated from the root bark of Murraya euchrestifolia Hayata. * Corresponding author. Fax: þ49 381 4986412; e-mail address: peter.langer@ uni-rostock.de (P. Langer). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2011.05.014 Tetrahedron 67 (2011) 5304e5318