Formal Total Synthesis of Palmerolide A

Abstract

A concise route to macrolactone 38, an advanced intermediate of the Nicolaou/Chen synthesis of palmerolide A, is described. Key steps in our synthesis include a Noyori transfer hydrogenation of an alkynone, chain extension via Claisen rearrangement, and an ADH reaction on an enyne. After reduction of the triple bond, a selective silylation served to differentiate the hydroxy­ groups of the diol, which allowed for the preparation of aldehyde 30 containing already the carbamate function. A HWE reaction produced the substrate for an intramolecular Heck coupling. In contrast to the Stille cyclization, the Heck cyclization produced only the desired 14E,16E-diene. Elaboration of the C-19 side chain led to the key lactone 38.

Key words

asymmetric synthesis - dihydroxylations - Heck reaction - macrocycles - natural products

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