Stereoselektive Cascade Aldol Reactions for Expeditious. Total Synthesis of Polyketide Natural Products
Final Report Abstract
In summary, we have developed the first Mukaiyama cross-aldol addition of silyl enol ethers derived from α-halogenated acetaldehydes. Furthermore, we have successfully applied this reaction in a sequential manner allowing for rapid, highly stereoselective construction of novel halogenated polyketide-like fragments. The first aldol addition of the Z-halo silyl enol ethers furnishes anti-β-siloxy-α-haloaldehydes in remarkably high diastereoselectivities. The subsequent addition is Felkin-selective and yields syn-syn-anticonfigured β,δ-bissiloxy-α,γ-bishalo-aldehydes. Moreover, by switching solvent, all-syn double aldol product was also obtained. Furthermore, we have developed a remarkably general and highly anti-stereoselective Mukaiyama aldol reaction of silyl enol ethers derived from α-halogeneted ketones. Finally, we have successfully incorporated these haloketone-derived silyl enol ethers into our onepot sequential-aldol methodology which allows for a rapid, diastereoselective, and flexible construction of syn-syn-anti-configured 3,5-bissiloxy-2,4-bishaloketones. Overall, the developed methodology allows for a rapid preparation of novel, halogenated polyketide fragments featuring up to four contiguous stereocenters. This methodology offers a step-economic access to a synthetically valuable and potentially highly pharmacophoric architectures, which are not easily accessible by other methods.
Publications
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"Rapid, One-Pot Synthesis of β- Siloxy-α-Haloaldehydes” J. Am. Chem. Soc. 2011, 133, 14248-14251
J. Saadi, M. Akakura, H. Yamamoto
