American Chemical Society
jo0623890_si_003.pdf (3.9 MB)

Nickel-Catalyzed Coupling Producing (2Z)-2,4-Alkadien-1-ols, Conversion to (E)-3-Alkene-1,2,5-triol Derivatives, and Synthesis of Decarestrictine D

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journal contribution
posted on 2007-03-02, 00:00 authored by Yuichi Kobayashi, Shinya Yoshida, Moriteru Asano, Akira Takeuchi, Hukum P. Acharya
The 3-alkene-1,2,5-triol structure is not only a major framework of biologically important molecules but also a new functional-group-rich unit for synthesis of polyols and sugars. A method furnishing such triol derivatives 8 was developed and successfully applied to synthesis of decarestrictine D (18). First, coupling reaction of the unprotected alcohols 2 with borates 4 was investigated to produce the dienyl alcohols 6 with NiCl2(dppf) in Et2O/THF (5:1) at room temperature. The hydroxyl-group-directed epoxidation of 6 followed by palladium-catalyzed reaction with AcOH (Scheme ) furnished 3-alkene-1,2,5-triol derivatives 8. Since each step proceeded with high stereo- and regioselectivities, the stereochemistry of 8 has been correlated with the olefin geometry of 6. With the above transformation in mind, synthesis of the full carbon skeleton of decarestrictine D (18) could be designed easily and was completed successfully. Furthermore, a new seco acid 19b with the MOM protective group for the three hydroxyl groups was found to afford macrolide 48 in a yield higher than those reported previously.