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A convergent strategy for synthesis of asimicin that features two highly stereoselective chelate-controlled [3+2] annulation reactions that set all the stereo-chemistry of the bis-tetrahydrofuran unit are developed. Efforts are made to extend this strategy to other members of the acetogenin family.

Double asymmetric [3 + 2]-annulation reactions of chiral β-silyloxyallylsilanes with chiral 2-tetrahydrofuranyl carboxaldehydes have been studied, leading to the stereocontrolled synthesis of six diastereomeric bis-tetrahydrofuran structures corresponding to the core subunits of members of the Annonaceous acetogenin family of natural products. Transition-state models are proposed to account for the stereoselectivity of the double-stereodifferentiating [3 + 2]-annulation reactions. [ABSTRACT FROM AUTHOR]

The article reports that Annonaceous acetogenins are a structurally diverse group of natural products isolated from the Annonaceae family. The acetogenins contain a long aliphatic backbone bearing a terminal butenolide unit and one or more tetrahydrofuran rings at internal positions of the aliphatic chain. The annulation reaction of allylsilanes and aldehydes in the presence of Lewis acids is an important method for the synthesis of substituted tetrahydrofuran and other five-membered heterocycles. Here the authors develop a convergent strategy for synthesis of asimicin that features two highly stereoselective chelate- controlled annulation reactions that set all of the stereochemistry of the bis-tetrahydrofuran unit.

[reaction: see text] A total synthesis of (+)-bullatacin has been accomplished via a diastereoselective [3+2] annulation reaction of the highly enantiomerically enriched allylsilane 3 and racemic aldehyde 4, which provides the key bis-tetrahydrofuran fragment 15 with > or = 20:1 ds.

[reaction: see text] The protiodesilylation of unactivated C(sp3)-SiMe2Ph bonds proceeds efficiently by treatment with tetrabutylammonium fluoride in wet DMF or THF via isolable dimethylsilanol intermediates.