Iodine as a mild and efficient catalyst for the diastereoselective synthesis of d-silyloxy-c-lactones J. S. Yadav * , B. V. Subba Reddy, G. Narasimhulu, G. Satheesh Division of Organic Chemistry, Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad 500 007, India article info Article history: Received 24 January 2008 Revised 12 July 2008 Accepted 16 July 2008 Available online 19 July 2008 Keywords: Mukaiyama aldol Molecular iodine Aldehydes c-Lactones Silyloxyfuran abstract Aldehydes undergo smooth nucleophilic addition with 2-trimethylsilyloxyfuran in the presence of 10 mol % of iodine under mild and neutral conditions to produce the corresponding d-silyloxy-a,b-unsat- urated-c-lactones in high yields and with moderate diastereoselectivity. ortho-Substituted benzalde- hydes afford the syn-isomer predominantly. The use of iodine makes this procedure quite simple, more convenient and cost-effective. Ó 2008 Published by Elsevier Ltd. Lewis acid-catalyzed carbon–carbon bond forming reactions are of prime importance in organic synthesis because of their mild reaction conditions, unique reactivity and improved selectivities. 1 Butenolides (a,b-unsaturated-c-lactones) are versatile building blocks for the synthesis of several biologically active natural prod- ucts such as cavernosine, 2 A26771B 3 and many others. 4 The cata- lytic coupling of 2-(trimethylsilyloxy)furan with aldehydes in the presence of Lewis acids is one of the most efficient methods for the synthesis of d-hydroxy-a,b-unsaturated-c-lactones. 5 Lewis acids such as BF 3 ÁOEt 2 , TMSOTf, ZnCl 2 , TiCl 4 , SnCl 4 , SiCl 4 and silyl triflates have been known to catalyze this reaction under strictly anhydrous conditions. 6,7 The presence of even a small amount of water results in lower yields probably due to the rapid decomposi- tion or deactivation of the promoters. Recently, bismuth triflate was found to catalyze this reaction at low temperature (À78 °C). 8 However, the high cost, stringent conditions and moisture sensitiv- ity of some of these reagents limit their use in large scale synthesis. Therefore, the development of new reagents that are more efficient leading to convenient procedures with improved yields and selec- tivity is desirable. Recently, molecular iodine has received considerable attention as an inexpensive, non-toxic and readily available catalyst for var- ious organic transformations affording the corresponding products with high selectivity and in excellent yields. The mild Lewis acidity associated with iodine has enhanced its use in organic synthesis to perform several organic transformations using stoichiometric levels to catalytic amounts. 9 In continuation of our interest on catalytic applications of molecular iodine, 10 we herein report a simple, convenient and metal free synthesis of d-silyloxy-a,b-unsaturated-c-lactones by means of coupling of 2-(trimethylsilyloxy)furan with various alde- hydes under mild conditions. Thus, treatment of 2-(trimethylsilyl- oxy)furan (1) with benzaldehyde (2) in the presence of 10 mol % of I 2 afforded the corresponding d-silyloxy-a,b-unsaturated-c-lactone in 89% yield as a mixture of syn:anti-isomers (3a/4a, 70:30; Scheme 1). This result provided the incentive for further study with aldehydes such as 2-methoxy-, 2,5-dimethoxy-, 2,4-dimethoxy-, 3,4,5-trimethoxy-, 4-methyl-, 4-nitro-, 4-chloro- and 3,4-methyl- enedioxy-benzaldehyde. Interestingly, these substituted aryl 0040-4039/$ - see front matter Ó 2008 Published by Elsevier Ltd. doi:10.1016/j.tetlet.2008.07.085 * Corresponding author. Tel.: +91 40 27193434; fax: +91 40 27160512. E-mail address: yadav@iict.res.in (J. S. Yadav). 10 mol% I 2 CH 2 Cl 2, r.t. syn (major) anti (minor) O OTMS Ph-CHO + O O OTMS Ph O O OTMS Ph 1 2 3a 4a + Scheme 1. Reaction of benzaldehyde with 2-(trimethylsilyloxy)furan. Tetrahedron Letters 49 (2008) 5683–5686 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet