Tandem C-3/C-2 annulation of indole, benzofuran, and benzothiophene with 2-alkynyl benzylalcohol: an efficient approach to the diverse tetracyclic heteroazulene ring systems Soumen Sarkar, Krishnendu Bera, Umasish Jana ⇑ Department of Chemistry, Jadavpur University, Kolkata 700 032, West Bengal, India article info Article history: Received 25 June 2014 Revised 8 September 2014 Accepted 10 September 2014 Available online 20 September 2014 Keywords: Tandem Annulation Heteroazulene Atom-efficient Iodine abstract We demonstrate an efficient and flexible strategy toward the synthesis of a library of biologically and pharmaceutically important tetracyclic heteroazulene derivatives in the presence of inexpensive and less toxic molecular iodine. The present strategy involves a sequential alkylation and alkenylation of indole/ benzofuran/benzothiophene with o-alkynyl benzyl alcohols derivatives to obtain tetracyclic heteroazu- lene derivatives in moderate to good yields. Compared to other methodologies, the present strategy is more general, versatile, and environmentally friendly. Ó 2014 Elsevier Ltd. All rights reserved. Polycyclic indole derivatives have received considerable atten- tion from the science community due to their occurrence in bioactive natural products and pharmaceutically important com- pounds. 1 In particular, cyclohepta[b]indoles are very important building blocks as they are widely found in a large number of bio- logically active natural products such as silicine, 2a ervistine, 2b,2c and actinophyllic acids. 2d In addition, cyclohepta[b]indole deriva- tives are also important structural motifs in numerous pharmaceu- tical agents with a broad spectrum of pharmacological activities ranging from anti-inflammation, 3 anti-cancer, 4 and anti-aging 5 to anti-tuberculosis activities. 6 For instance, carboxamide A acts as a potent and selective inhibitor of the deacetylase SIRT1 (Scheme 1). 3b Compound B, inhibits the adipocyte fatty-acid bind- ing protein (A-FABP) (Scheme 1). 7 Tricyclic compound C is an antitubercular agent (Scheme 1), 8 and many tetracyclic indole derivatives with seven-membered ring have shown promising bioactivity such as compounds D, E, and F 9 are useful anticancer agents (Scheme 1). Similarly, seven-membered- ring-fused benzofuran derivatives are a class of natural or synthetic polycycles that display a wide range of biological activities 10a,b such as antimicrobial, 10c cytotoxic, 10d antiulcer, 10e and anti-inflamma- tory activities. 10f Moreover, numerous polycyclic benzothiophene based compounds have also received attention from organic chemists. 11 Consequently, synthesis of cyclohepta[b]heterocycles received much attention from the organic chemist. Sequential reactions have received great attention in terms of reaction efficiency because several bonds can be formed in a single step. Very recently, a few elegant strategy have been developed for the synthesis of tricyclic cyclohepta[b]indole derivatives via sequential reactions such as, gallium(III)-catalyzed three- component coupling of indole, aldehydes and dienes, 12a Rh- and Pt-catalyzed [4+3] cycloaddition of dienes with concomi tant http://dx.doi.org/10.1016/j.tetlet.2014.09.050 0040-4039/Ó 2014 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. Tel.: +91 03324146666x2535; fax: +91 33 2414 6584. E-mail address: jumasish2004@yahoo.co.in (U. Jana). N N N R O anticancer agent antitumor N CONH 2 A-FABP inhibitor CO 2 H N H CONH 2 SIRT1 inhibitor N H anti-tubercular agent Cl N O Cl N N HN N anticancer agent C A B E D F Scheme 1. Few biologically active cyclohepta[b]indoles. Tetrahedron Letters 55 (2014) 6188–6192 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet