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Application of the Silicon-Tether Strategy for Controlling the Regioselectivity and Diastereoselectivity of Intramolecular Nitrone Cycloadditions for Aminopolyol Synthesis

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journal contribution
posted on 29.07.2000, 00:00 by Teruhiko Ishikawa, Takayuki Kudo, Kazunori Shigemori, Seiki Saito
Highly regioselective and diastereoselective intramolecular chiral nitrone cycloaddition reactions with a vinyl group tethered by a silicon atom have been developed as a general method for the synthesis of stereodefined amino polyols. This strategy features a series of one-pot reactions involving (1) DIBAH reduction of the carbonyl groups of chiral α- or β-hydroxy carbonyl compounds, in which the hydroxy group is protected as diphenylvinylsilyl ethers, at −78 °C to give an aldehyde, (2) condensation of the aldehyde with N-benzylhydroxylamine to furnish nitrone (−78 °C → rt), and (3) intramolecular [3 + 2] dipolar cycloaddition reaction between the nitrone and the silicon-tethered vinyl group (rt → 70 °C, 3−15 h) to give isoxazolidine derivatives as direct precursors for amino polyols. Since the cycloaddition reaction is concerted in nature and passes through a fused-bicyclic transition state, the substituents, the nitrone substrate, and the silicon atom bias the stereochemical course of this addition, resulting in highly diastereoselective and synthetically useful transformations.