No abstract

No abstract

A simple, efficient and cost effective method for a divergent synthesis of benzoxepine derivatives using a hitherto unreported, highly regioselective, tandem iodocyclization procedure is described.A wide range of natural products possess a seven-membered oxacycle in their molecular architecture. 1 Moreover, these units serve as target molecules in numerous synthetic studies. 2 The benz[b]oxepine ring system occurs in a small number of biologically active natural products isolated mainly from plant sources. 3 Some of these compounds exhibit oral hypotensive and antiulcer properties. 4 The fungal metabolites pterulone and its analogue 5 inhibits the eukaryotic respiratory chain at the NADH site of the ubiquinone oxidoreductase, possesses potent antifungal activity and are only weakly cytotoxic ( Figure 1). On the other hand, Pterulinic acid also exhibits significant antifungal and either weak or no cytotoxic activity, and is an effective inhibitor of eukaryotic respiration. 6 Figure 1Many synthetic methods, including palladium-mediated intramolecular Heck reaction, 7 RCM 8 and transition-metal-mediated cyclizations, 9 have been utilized for the construction of medium-sized heterocycles, especially oxepines and oxocine derivatives. Recently we have successfully synthesized medium-ring heterocycles based on a sulfanyl radical addition and cyclization procedure, 10 but sometimes these methods suffer from complex reaction conditions, difficulty in separation of products and from the toxicity of thiophenol. Recent activity in the study of biologically active oxepines and oxepanes has required the search for versatile, cost effective reagents and simple reaction conditions for the synthesis of these heterocycles. During the last few years iodine has found wide utility because it is an inexpensive, non-toxic and readily available electrophilic reagent that enables iodocyclization reactions to generate compounds with synthetic and biological applications. 11 Iodocyclization of heteroatoms with tethered alkynes has been found to be an effective and high-yielding method of preparing a large number of heterocyclic compounds, e.g., furans, 12 pyrroles, 13 indoles, 14 benzo[b]furans 15 and benzo[b]thiophenes. 16 Iodonium-promoted heteroannulations are quite attractive because they offer an alternative protocol for the synthesis of complex molecules that are not always accessible using common organometallic reagents. Although many examples are available for the construction of five-and sixmembered heterocycles utilizing iodine-mediated cyclization, to our knowledge, the synthesis of medium-ring heterocycles has not been reported so far. These findings prompted us to undertake a study on iodine-mediated cyclizations for the synthesis of benzoxepine derivatives. These would provide an alternative and easy procedure for the construction of some benzoxepine skeletons, which are present as a basic structural moiety in a number of naturally occurring compounds. Herein we report the results.The required precursors 3a-d for our prese...

The synthesis of oxocines and oxepines is difficult. Two efficient protocols have been developed for the construction of naphthoxepine and naphthoxocine derivatives by sequential Wittig olefination and intramolecular Heck reaction.

No abstract