Synthesis of a novel, bowl-like bis c-lactone Faiz Ahmed Khan, * Vineet Dwivedi and Bhimsen Rout Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India Received 2 October 2006; revised 25 October 2006; accepted 10 November 2006 Abstract—Synthesis of a compound with bowl-like, symmetrical molecular architecture, starting from a Diels–Alder adduct 7, derived from a reaction between 2,5-dihydro-2,5-dimethoxyfuran and 1,2,3,4-tetrachloro-5,5-dimethoxycyclopentadiene, is reported. Ó 2006 Elsevier Ltd. All rights reserved. Syntheses of bowl-like molecular architectures with oxy- gen atoms at the apex positions, called oxa-bowls, have attracted considerable interest. 1 Such aesthetically pleas- ing but synthetically challenging molecules, endowed with interesting physicochemical properties, are poten- tial targets for exploration into new avenues of applica- tion. One such emerging application is in the area of neuroscience where the metal binding property of an oxapentacyclic amine derivative is exploited as a neuro- protective agent in focal ischemia due to its calcium channel antagonism activity. 2 Hence, the quest for poly- cyclic cage compounds, bearing one or more hetero- cycles, through novel and efficient pathways continues. 3 Oxa-bowl Pentaoxa[5]peristylane O O O O O We have previously reported an efficient ruthenium- catalyzed methodology for the synthesis of norbornyl a-diketones, 4 serving as versatile building blocks for the construction of natural as well as unnatural prod- ucts. 5 During the course of our studies directed towards the synthesis of c-lactones from norbornyl a-diketones, 6 we demonstrated that one of the products obtained in 30% yield in the ruthenium-catalyzed oxidation of diol 1 was an interesting derivative 2. 6a We envisaged that this could serve as a potential precursor for the bowl- like molecule 4 through oxidation as indicated in Scheme 1, either at the tetracyclic hemiacetal stage 2 or at the tricyclic monolactone stage 3 obtained after cleavage of the precursor. We herein, report our efforts in this direction and provide an account of a de novo synthesis of bowl-like bis c-lactone 4. The tetracyclic hemiacetal 2 was subjected to cleavage using lead tetraacetate in methanol to give tricyclic monolactone 3 (Scheme 1). Although ruthenium-cata- lyzed oxidation of the tetrahydrofuran moiety at the a-position is generally very easy, 7 tricyclic monolactone 3, under usual reaction conditions, was recovered in 73% yield. A similar observation was also noted for the tetra- cyclic hemiacetal 2. 0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2006.11.062 * Corresponding author. Tel.: +91 512 2597864; fax: +91 512 2597436; e-mail: faiz@iitk.ac.in ref. 6a O Cl O O O O Cl OMe MeO O Cl O O Cl OMe MeO CO 2 Me Cl Cl OMe MeO Cl Cl OH OH Cl Cl OMe MeO O O O O H RuO 4 Oxidation 1 2 3 4 rt, 2 h, 63% Pb(OAc) 4 , MeOH Scheme 1. Tetrahedron Letters 48 (2007) 207–209