Oxepane

Abstract: The total synthesis of hemibrevetoxin B (1) and (7aα)-epi-hemibrevetoxin B (2) is described. The synthesis of the epimer (2) was achieved through a convergent approach involving coupling of the carboxylic acid 17 carrying the bicyclic pyran system with the hydroxy compound 31 containing the monocyclic pyran system, thionation of the resulting diester 32 to the dithionoester 33, photolytic closure to the oxepane enol ether 34, and hydroxy ketone cyclization to the dioxepane system 40. The Z-diene system was established using a selenyl-Wittig reaction followed by syn elimination of the selenoxide to the diene. The α-vinyl functionality was installed using the Eschenmoser's salt methodology. The synthesis of hemibrevetoxin B (1) was achieved through a linear approach involving sequential formation of the oxepane rings (65 → 67 → 73) using the method of thionolactone formation followed by nucleophilic addition and regio/stereoselective hydroboration (67 → 68, 75 → 76). Elaboration of the side chains was carried out in a similar fashion as described for the epimer. The streochemistry of the ring junctures in 1 and 2 and intermediates leading to them was established by X-ray cristallographic analysis carried out on compounds 45 and 54

Abstract: Strategies for the synthesis of polycyclic ethers based on intramolecular allylations are overviewed. The intramolecular condensation of allylic stannanes and aldehydes is a powerful tool for the synthesis of oxepane derivatives. The reaction is successfully applied to the iterative total synthesis of hemibrevetoxin B (2). Further, the intramolecular allylation of alpha-acetoxy ethers provides an efficient method for the convergent synthesis of polycyclic ethers. The usefulness of the latter strategy is demonstrated in the convergent total synthesis of gambierol (4).