Title: Iodine-Catalyzed One-Pot Synthesis of 2H-Pyrans by Domino Knoevenagel/6π-Electrocylization
Abstract: 2H-Pyrans are important core units in a number of natural products1 and also in photochromic materials.2The molecules bearing 2H-pyrans have a variety of interesting biological ac tivities and potential medical applications.32H-Pyrans were prepared earlier using piperidine or BF3-Et2O as a catalyst.4We have been developed the methodologies for the synthesis of 2Hpyrans through indium(III) chloride-or EDDA-catalyzed formal [3+3] cycloaddition as a Lewis acid5 or a Bronsted acid and base catalyst.6Later, novel approaches for the synthesis of 2H-pyrans were also developed by other groups using TiCl% and In(OTf)3 Lewis acids as a catalyst7 and phosphoric acid as a Bronsted acid catalyst.8Although several synthetic approaches for construc ting 2H-pyrans derivatives have been reported by us5,6 and other groups,7,8 more simple and cost-effective approaches are still demand because of their importance.Recently, iodine has been received considerable attention as an inexpensive and readily available catalyst for various orga nic reactions.9Iodine-catalyzed Suzuki-Miyaura coupling reac tion,10 dehydration of tertiary alcohols to alkenes,11 esterifica tions,12 transesterification,13 acetylation,14 protection15 or depro tection16 of acetals, N-Boc protection of amines,17 and Michael addition18 were described by many groups.Iodine-catalyzed and -mediated syntheses of benzyl alkyl ethers,19 benzothiophenes,20 bis-indols,21 卩-keto enol ethers,22 chalcones,23 quinolines,24 and isoquinolines25 were already reported.However, iodine-cataly zed formal [3+3] cycloadditon of 1,3-carbonyls to a*-unsaturated aldehydes to afford 2H-pyrans has not been examined.We report herein a convenient and efficient one-pot synthesis of 2H-pyrans by a domino Knoevenagel/6n-electrocyclic reaction.As shown in Scheme 1, the crucial strategy that we have de veloped begins with reactions of cyclic 1,3-dicarbonyls to a,卩unsaturated aldehydes in the presence of iodine as an inexpen sive and readily available mild catalyst.Reaction of dimedone (1) with 3-methyl-2-butenal in the pre sence of 20 mol% of iodine using several solvents first investi gated (Table 1).The best yield (94%) was obtained in refluxing