Dinuclear Asymmetric Zn Aldol Additions: Formal Asymmetric Synthesis of Fostriecin

Abstract
Direct asymmetric aldol reactions constitute a powerful methodology for the efficient synthesis of complex natural products. Herein we report the first application of our recently reported dinuclear Zn-catalyzed direct aldol addition of alkynyl ketones to aldehydes in a short and efficient formal asymmetric synthesis of fostriecin, a potent cyctotoxic natural product. This work highlights not only the power of the aldol methodology but also the utility of the akynyl silane aldol adducts, as it is subsequently utilized in a vinyl silane cross-coupling reaction which affords the target molecule in 14 steps for the longest linear sequence in 8.5% overall yield.

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