Studies Toward the Synthesis of Leiodolide A

Studies have described a highly convergent plan toward the synthesis of leiodolide A (1), a potent cytotoxic sponge metabolite. The enantiocontrolled preparation of aldehyde 6 is achieved with the application of several advances in methodology for the synthesis of substituted 1,3-oxazoles. Efforts have examined the halogen dance reaction, the selectivity of Stille cross coupling reactions of 4-bromo-1,3-oxazoles, and nucleophilic displacement of the 2-phenylsulfonyl substituent with organolithium reagents as preparatively useful reactions. These techniques have facilitated the efficient synthesis of 6 from the starting bromide 12, alkenylstannane 16, and the primary nonracemic alcohol 25.