Synthesis of 6H-benzo[c]chromen-6-ones by cyclocondensation of 1,3-dicarbonyl compounds with 4-chloro-3-formylcoumarin Viktor O. Iaroshenko a,b,⇑ , Muhammad S.A. Abbasi a , Alexander Villinger a , Peter Langer a,c,⇑ a Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany b National Taras Shevchenko University, 62 Volodymyrska Str., 01033 Kyiv-33, Ukraine c Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany article info Article history: Received 8 June 2011 Revised 27 July 2011 Accepted 29 July 2011 Available online 16 August 2011 Keywords: Cyclizations, Domino reaction Coumarins Benzo[c]chromen-6-ones Heterocycles abstract 6H-benzo[c]chromen-6-ones were prepared by base mediated cyclocondensation of 1,3-dicarbonyl com- pounds with 4-chloro-3-formylcoumarin. Ó 2011 Elsevier Ltd. All rights reserved. Benzo[c]chromen-6-ones (biaryl lactones) are of considerable pharmacological relevance and occur in various natural products, such as autumnariol, autumnariniol, alternariol, altenuisol, ellagic acid, or coruleoellagic acid ( Fig. 1). 1,2 Benzo[d]naphthopyran-6- ones, such as defucogilvocarcin V, gilvocarcins, chrysomycins, and ravidomycins, 3 also occur in nature and exhibit a wide range of pharmacological activities, such as antimicrobial and antitumor activity. Other pharmacological activities include inhibition of endothelic cells 4 and oestrogene receptor 5 growth. H-Benzo[c]chromen-6-ones are available by intramolecular Pd(II)-catalyzed coupling reactions of aryl benzoates. 6 Snieckus et al. developed an efficient approach to 6H-benzo[c]chromen-6- ones by directed ortho-metalation (DoM) and subsequent Suzuki reaction. 3 In addition, 6H-benzo[c]chromen-6-ones have been prepared by palladium-catalyzed reaction of CO with boroxarenes derived from ortho-hydroxybiaryls. 7 6H-Benzo[c]chromen-6-ones were also prepared by cyclization reactions of 1,3-bis(silyloxy)- 1,3-butadienes. 8,9 Recently, we have reported 10 the synthesis of functionalized 9-hydroxy-6H-benzo[c]chromen-6-ones by cycliza- tion of 1,3-bis(silyloxy)-1,3-butadienes with readily available 11 4- chloro-3-formylcoumarin (4-chloro-2-oxo-2H-chromene-3-carbal- dehyde). Herein, we report a convenient synthesis of 6H- benzo[c]chromen-6-ones by base mediated cyclocondensations of 1,3-dicarbonyl compounds with 4-chloro-3-formylcoumarin. In contrast to the reactions mentioned above, the reactions reported herein follow a 2:1 instead of a 1:1 stoichiometry and proceed by double nucleophilic attack of the dicarbonyl compound to the coumarin and subsequent cyclization. 12 The K 2 CO 3 mediated reaction of b-ketoester 2a (1.0 equiv) with 4-chloro-3-formylcoumarin (1) afforded 6H-benzo[c]chromen-6- one 3a, albeit, in only approx. 10% yield. The yield of 3a was dramatically increased (75%) when 2.0 equiv of 2a was employed 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.07.140 ⇑ Corresponding authors. Fax: +49 381 4986412. E-mail addresses: viktor.iaroshenko@uni-rostock.de (V.O. Iaroshenko), peter.- langer@uni-rostock.de (P. Langer). O O OH HO OH OH O O Ellagic acid O O Gilvocarcin M H 3 CO HO CH 3 H 3 CO O HO HO H 3 C H OH O O OH OH CH 3 HO Alternariol Figure 1. Natural products with benzo[c]chromen-6-one subunit. Tetrahedron Letters 52 (2011) 5910–5912 Contents lists available at SciVerse ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet