Synthesis of 4-hydroxy- and 2,4-dihydroxy-homophthalates by [4þ2] cycloaddition of 1,3-bis(silyloxy)-1,3-butadienes with dimethyl allene-1,3-dicarboxylate Ibrar Hussain a , Mirza A. Yawer a , Bettina Appel a , Muhammad Sher a, b , Ahmed Mahal a , Alexander Villinger a , Christine Fischer b , Peter Langer a, b, * a Institut fu ¨r Chemie, Universita ¨t Rostock, Albert-Einstein-Strasse 3a, 18059 Rostock, Germany b Leibniz-Institut fu ¨r Katalyse e. V. an der Universita ¨t Rostock, Albert-Einstein-Strasse 29a, 18059 Rostock, Germany article info Article history: Received 13 May 2008 Received in revised form 26 May 2008 Accepted 29 May 2008 Available online 3 June 2008 abstract The reaction of 1,3-bis(trimethylsiloxy)-1,3-butadienes with dimethyl allene-1,3-dicarboxylate provides a convenient and regioselective approach to a variety of functionalized 4-hydroxy- and 2,4-dihydroxy- homophthalates. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction Allenes represent versatile synthetic building blocks in inter- and intramolecular [4þ2] cycloadditions. 1 The [4þ2] cycloaddition of 2-silyloxy-1,3-dienes with allenes has been reported to give functionalized phenols. For example, (R)-(þ)-lasiodiplodin was prepared based on the cyclization of a cyclic allenylester with 1,1- dimethoxy-3-trimethylsilyloxy-1,3-butadiene. 2 The reaction of allenylphenylsulfone with Danishefsky’s diene afforded 3-methyl- 4-(phenylsulfonyl)-phenol. 3 Roush and Murphy were the first to report the cycloaddition of 1-methoxy-1,3-bis(trimethylsilyloxy)- 1,3-butadiene with dimethyl allene-1,3-dicarboxylate. 4 Some years ago, we reported the synthesis of various homophthalates based on the cycloaddition of dimethyl allene-1,3-dicarboxylate with various 1,3-bis(silyl enol ethers). 5 Later on, this methodology was suc- cessfully applied to the synthesis of an analogue of lactonamycin, 6 of the N 7 –C 25 fragment of psymberin, 7 and of the 4-acetylisocou- marins AGI-7 and sescandelin (Scheme 1). 8 Herein, we report full details of the methodology and a study related to the preparative scope. 2. Results and discussion The reaction of 1-ethoxy-1,3-bis(trimethylsilyloxy)-1,3-butadi- ene (1a), prepared from ethyl acetoacetate in two steps, 9,10 with dimethyl allene-1,3-dicarboxylate (2), available from dimethyl acetone-1,3-dicarboxylate, 11 afforded the homophthalate 3a in up to 75% yield (Scheme 2). The best yield was obtained when a mix- ture of the starting materials (neat) was stirred for 20 h at 20  C. Subsequently, to the mixture was added an ethanol solution of triethylammonium fluoride. 12 The formation of 3a can be explained O HO O OH HO sescandelin O O O OH HO AGI-7 Scheme 1. Structure of ()-sescandelin and AGI-7. OSiMe 3 Me 3 SiO OEt + 1a CO 2 Me CO 2 Me Me 3 SiO OSiMe 3 CO 2 Me MeO 2 C H H 2 neat CO 2 Me CO 2 Me HO OH EtO A HNEt 3 F EtOH CO 2 Me CO 2 Me O OH EtO B 3a (42%) _ 2Me 3 SiF EtOH _ 20 °C 20 h Scheme 2. Possible mechanism for the formation of 3a. * Corresponding author. Tel.: þ49 381 4986410; 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/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2008.05.118 Tetrahedron 64 (2008) 8003–8009