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Thesis

New developments on silyl 2-alkenyl sulfinates and their applications to the asymmetric synthesis of polypropionate fragments

Sulphur dioxide reacts with 1-oxydienes generating zwitterions which are quenched by enoxysilanes to form substituted silyl alkenylsulfinates. These intermediates are desilylated with Bu4NF and the resulting sulfinates react with MeI giving the corresponding methyl sulfones. This new SO2 reaction cascade, hetero-Diels-Alder addition of SO2/oxyallylation/alkylation, was expanded to a variety of electrophiles successfully. Several functional sulfones have been synthesized in modest to high yields. A number of chiral Lewis acids have been prepared and applied into this reaction cascade. Two common techniques were employed to analyze the enantiomeric excess in the resulted sulfones: chiral HPLC and chemical shift reagents. No interesting result was obtained. The removal of water in the reaction system indeed made the reaction better but did not lead to any increase in the enantioselectivity. Silyl sulfinate itself was found not to be able to catalyze the reaction. The formation of (E)-product was discovered in some cases. The introduction of another coordinating oxy-substitution into the dienes did not change the reaction. So the asymmetric catalytic version could not be realized. Silyl sulfinates were found to undergo the silicon/palladium transmetallation. This process could be realized by catalysis with either Pd(PPh3)4 or Pd(OAc)2. The driving force is the formation of silyl acetate. When the sulfinyl palladium complex forms, it can undergo either reductive elimination to give allyl sulfones, or elimination of SO2 in the presence of proton source, such as isopropanol or methanol, giving retro-ene products in good yields. The success of the reactions depended on the amount of the ligand, the solvent and the temperature. More ligand, such as triphenylphosphine, and THF as solvent favor the reductive elimination, while less ligand and CH3CN as solvent favor the retro-ene reaction. The reaction mechanism was studied by NMR experiments which afforded the direct proofs for transmetallation reactions. Kinetic studies on the decomposition of simple silyl alkenylsulfinate into retro-ene products indicated that the cleavage of silicon-oxygen bond could be simply realized by isopropanol. CD3CN was found to have an enormous solvent effect. The presence of Pd(II) species made the reaction somehow faster and cleaner. Related with the studies above it was discovered that trialkylsilyl 2-methylprop-2-enesulfinates are good silylation reagents. For TMS and TES sulfinates, the reactivities were the same and led to 100% conversion in a few minutes for all kinds of alcohols. But for TBS sulfinate, the reactivity decreased significantly due to steric hindrance. Silyl sulfinates were also found to undergo silyl exchange with carboxylic anhydride and acetal/ ketal. The synthetic potential of the sequence hetero-Diels-Alder of SO2, quenching of zwitterions intermediate with an enoxysilane, desilylation and retro-ene elimination of SO2 was demonstrated by the synthesis of (βR,4R,5S,6R)-β,2,2,5-tetramethyl-6-{(1R)-1-[(4S,5S)-2,2,5-trimethyl-1,3-dioxan-4-yl]ethyl}-1,3-dioxane-4-ethanol, a known synthetic intermediate in the total, asymmetric synthesis of Rifamycin S.

    Thèse École polytechnique fédérale de Lausanne EPFL, n° 2985 (2004)
    Section de chimie et génie chimique
    Faculté des sciences de base
    Institut des sciences et ingénierie chimiques
    Jury: Manfred Mutter, Reinhard Neier, Joëlle Prunet, Albert Renken

    Public defense: 2004-4-26

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    Record created on 2005-03-16, modified on 2016-08-08

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