抄録
Welwitindolinone A isonitrile (1), isolated from the cyanobacteria Hapalosiphon welwitschii by Moore in 1994, has a unique structure in which an oxindole is spiro-fused to a functionalized bicyclo[4.2.0]octene core, and Baran and Wood have reported total synthesis of 1, independently . We recently demonstrated ruthenium(II)-catalyzed [2+2] cyclization of 1,7-allenynes leading to a bicyclo[4.2.0]octadiene skeleton. Here, we report synthetic study of Wood's synthetic intermediate 8 by using the ruthenium-catalyzed [2+2] cyclization as a key step. Allenynes 15a and 15b, which is a diastereomer of 15a with respect to propargylic hydroxy group, were prepared through coupling of diethyl malonate derivative 18 and allenylacetate 16 as a racemic form. Cyclization reactions of 15a and 15b were carried out in the presence of 10 mol% of Cp*RuCl(cod) in methanol at 50℃, and the corresponding bicyclic compounds 31a and 31b were obtained in good yields, respectively. After protection of propargylic hydroxy group of 31a and 31b, allylic oxidation of 32a and 32b under various conditions was investigated. However, no desired enone derivative 33 was obtained. Next, we examined hydroboration of 32a and 32b. As a result, reaction of 32b and BH_3.THF gave the alcohol derivative 37a, which had desired stereochemistry at the ring junction, along with its stereoisomer 37b. The alcohol 37a was oxidized by TPAP to give the corresponding ketone 34, from which transformation into the target compound 8 is currently in progress.
