A convergent synthesis of polycyclic ethers has been achieved by the intramolecular allylation of α-acetoxy ethers and subsequent ring-closing metathesis. The carboxylic acid 2 and alcohol 3 were connected by DCC coupling to give the ester 4 in 90% yield. After deprotection of the silyloxy group, the alcohol 5 was converted to the allylic stannane 8 via the mixed acetal 7 in good yield. The ester 8 was then subjected to the Rychnovsky protocol to give the α-acetoxy ether 9 as a mixture of diastereoisomers. The cyclization precursors 10-15 were prepared in a similar manner, and the results of the cyclization are summarized in Table 1. Treatment of 9 with 4 equiv of BF_3・OEt_2 gave a 70: 30 mixture of the cyclized products 16 and 17 in 79% yield (entry 1). Similarly, the cyclization of the substrates 10-15 proceeded stereoselectively to give the desired products in good yields (entries 2-7). We next examined the ring-closing metathesis of the products 18, 20, 22, 24, 25, and 27 (Table 2). Treatment of 18 with Grubbs catalyst 29 gave the tetracyclic ether 30 in 91% yield (entry 1). Similarly, the reactions of 20, 22, and 24 proceeded smoothly to afford the corresponding polycyclic ethers 31-33 in good yields (entries 2-4). Although the reactions of 25 and 27 with 29 were unsatisfactory, the use of the more active catalyst 34 provided the desired pentacyclic ethers 35 and 36 in high yield (entries 5 and 6). Based on these results, we have started the convergent synthesis of gambierol 1 and have synthesized the ABC and FGH ring segments, 48 and 60, from 2-deoxy-D-robose as shown in Schemes 2 and 3, respectively. Further studies toward the total synthesis of gambierol are now in progress in our laboratories.
