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Efficient Stereoselective Synthesis of a Key Chiral Aldehyde Intermediate in the Synthesis of Picolinamide Fungicides

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journal contribution
posted on 19.09.2019, 18:37 by Fangzheng Li, Steffen Good, Michael L. Tulchinsky, Gregory T. Whiteker
A highly stereoselective and efficient synthesis of (4S,5S,6S)-6-(benzyloxy)-5-phenoxy-4-propoxyheptanal, a key intermediate for syntheses of picolinamide fungicides, is described in this report. The synthesis features a scalable allylpropyl ether preparation, an efficient synthesis of the C1–C3 anti,syn-(S,S,S) stereotriad via a highly diastereoselective allylboration, and Cu-catalyzed phenylation of a sterically hindered secondary alcohol with BiPh3(OAc)2 followed by highly regioselective hydroformylation with the formation of a linear aldehyde. Excellent overall route efficiency was achieved (six steps and 39% yield) starting from readily available and inexpensive (S)-ethyl lactate.