Synthesis of Dibenzo[b,d]pyran-6-ones Based on [3 + 3] Cyclizations of 1,3-Bis(silyl enol ethers) with 3-Silyloxy-2-en-1-ones Ibrar Hussain, † Van Thi Hong Nguyen, † Mirza Arfan Yawer, † Tuan Thanh Dang, † Christine Fischer, ‡ Helmut Reinke, † and Peter Langer* ,†,‡ Institut fu ¨r Chemie, UniVersita ¨t Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany, and Leibniz-Institut fu ¨r Katalyse e.V. an der UniVersita ¨t Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany peter.langer@uni-rostock.de ReceiVed March 23, 2007 Functionalized dibenzo[b,d]pyran-6-ones were prepared by formal [3 + 3] cyclization of 1,3-bis(silyl enol ethers) with 3-silyloxy-2-en-1-ones or 1,1-diacetylcyclopropane to give functionalized salicylates, Suzuki cross-coupling reactions of the corresponding triflates, and subsequent BBr 3 -mediated lactonization. A second approach to dibenzo[b,d]pyran-6- ones relies on the [3 + 3] cyclization of 1,3-bis(silyl enol ethers) with 1-(2-methoxyphenyl)-1-(trimethylsilyloxy)alk- 1-en-3-ones and subsequent BBr 3 -mediated lactonization. Functionalized dibenzo[b,d]pyran-6-ones and related lactones are of pharmacological relevance and occur in a number of natural products, such as alternariol, 1 autumnariol, autum- nariniol 2 and altenuisol, 3 ellagic or coruleoellagic acid, 4 de- fucogilvocarcin V, gilvocarcins, chrysomycins, and ravidomy- cins. Known syntheses of dibenzo[b,d]pyran-6-ones rely on the cyclization of o-bromobenzoic acid with phenols, 5 intramolecu- lar Pd(II)-catalyzed coupling reactions, 6 and directed ortho- metalations (DOM) with subsequent Suzuki cross-coupling reactions. 7 Some years ago, Chan et al. reported an elegant approach to salicylates based on formal [3 + 3] cyclizations of 1,3-bis(silyl enol ethers) with 3-silyloxy-2-en-1-ones (Scheme 1). 8 Recently, we reported 9 the synthesis of dibenzo[b,d]pyran- 6-ones based on [3 + 3] cyclizations 10 of 1,3-bis(silyl enol ethers) 11 with 3-silyloxyalk-2-en-1-ones to give salicylates, Suzuki coupling of their triflates with o-methoxyboronic acids, and subsequent BBr 3 -mediated lactonization. Herein, we report full details of this work. In addition to our preliminary communication, 9 we also report a related approach to dibenzo- [b,d]pyran-6-ones based on what are, to the best of our knowledge, the first [3 + 3] cyclizations of 1,3-bis(silyl enol ethers) with 1-(2-methoxyphenyl)-1-(trimethylsilyloxy)alk-1-en- 3-ones. The chemistry reported complements known methods for the synthesis of dibenzo[b,d]pyran-6-ones. 1,3-Bis(silyl enol ethers) 1a-c were prepared, as previously reported, from methyl acetoacetate, ethyl acetoacetate, and methyl 4-methoxyacetoacetate, respectively. 8 4-(Silyloxy)pent- 3-en-2-ones 2a-g were prepared from acetylacetone, 3-methy- lacetylacetone, 3-ethylacetylacetone, benzoylacetone, 2-formyl- cyclohexanone, 2-acetylcyclohexanone, and 2-acetyltetralone, respectively. The TiCl 4 -mediated [3 + 3] cyclization of 1a-c with 2a-g afforded the salicylates 3a-h which were trans- formed into their triflates 4a-h (Scheme 2 and Table 1). The Suzuki reaction 12 of 4a-h with (2-methoxyphenyl)boronic acids 5a-c afforded biaryls 6a-k which were transformed into dibenzo[b,d]pyran-6-ones 7a-k (Scheme 3 and Table 2) by BBr 3 -mediated lactonization. 13 The [3 + 3] cyclizations pro- ceeded in moderate to good yields. The following steps (triflate formation, Suzuki reaction, and lactonization) proceeded, in most cases, in good to excellent yield. Recently, we reported the domino [3 + 3] cyclization/homo- Michael reaction of 1,3-bis(silyl enol ethers) with 1,1-diacyl- cyclopropanes. 14 These reactions proceed by cyclization and subsequent TiX 4 (X ) Cl, Br)-mediated cleavage of the cyclopropane moiety to give salicylates with a chlorinated or brominated side chain. The TiCl 4 -mediated cyclization of 1,3- bis(silyl enol ether) 1b with 1,1-diacetylcyclopropane (8) afforded, as previously reported, chloroethyl-substituted sali- cylate 3i which was transformed into triflate 4i. The Suzuki reaction of 4i with boronic acid 5a afforded 6l which was transformed into chloroethyl-substituted dibenzo[b,d]pyran-6- one 7l. The TiBr 4 -mediated cyclization of 1b with 8 afforded * To whom correspondence should be addressed. Fax: +381 4986412. † Institut fu ¨r Chemie. ‡ Leibniz-Institut fu ¨r Katalyse. (1) Raistrick, H.; Stilkings, C. E.; Thomas, R. Biochemistry 1953, 55, 421. (2) Tamm, C. Arzneim.-Forsch. 1972, 22, 1776. (3) Pero, R. W.; Harvan, D.; Blois, M. C. Tetrahedron Lett. 1973, 14, 945. (4) (a) Sayer, J. M.; Haruhiko, Y.; Wood, A. W.; Conney, A. H.; Jerina, D. M. J. Am. Chem. Soc. 1982, 104, 5562. (b) Gunawardana, Y. A. G. P.; Kumar, N. S.; Sultanbawa, M. U. S. Phytochemistry 1979, 18, 1017. (5) Hurtley, W. R. H. J. Chem. Soc. 1929, 1870. (6) Bringmann, G.; Reuscher, H. Tetrahedron Lett. 1989, 30, 5249. (7) Alo, B. I.; Kandil, A.; Patil, P. A.; Sharp, M. J.; Siddiqui, M. A.; Snieckus, V. J. Org. Chem. 1991, 56, 3763. (8) (a) Chan, T.-H.; Brownbridge, P. J. Am. 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