The cycloaddition reaction of acylketenes with vinyl ethers affords an extremely direct route to 2,6-dideoxysugars and their methyl ethers. The lithium enolate of commercial 2,6,6-trimethyldioxinone 3 was fluorinated in good yield to afford fluorinated dioxinone 8. An illustrative range of fluorinated 2,6-dideoxysugar derivatives was prepared via the acetyl ketene-vinyl ether cycloadduct. Electronic structure calculations were carried out to investigate the effect of the fluorine atom on ease of formation and subsequent reaction of the (fluoroacetyl) ketene reactive intermediate. A single fluorine atom lowers the barrier to fragmentation by ca. 7.5 kJ mol(-1), consistent with experimental findings, but has almost no effect on the barrier to rate determining vinyl ether addition, or to oxoketene dimerisation.
- conjugated ketenes
- deoxy sugars
Audouard, C., Bettaney, K., Doan, C. T., Rinaudo, G., Jervis, P. J., & Percy, J. M. (2009). An appraisal of oxoketene cycloaddition methodology for the synthesis of 2,6-dideoxysugars and fluorinated 2,6-dideoxysugars. Organic and Biomolecular Chemistry, 7(8), 1573-1582. https://doi.org/10.1039/b817672h