An appraisal of oxoketene cycloaddition methodology for the synthesis of 2,6-dideoxysugars and fluorinated 2,6-dideoxysugars.
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.
Audouard
Christophe
C
Department of Chemistry, University of Leicester, University Road, Leicester, UK LE1 7RH.
Bettaney
Kim
K
Doan
Châu T
CT
Rinaudo
Giuseppe
G
Jervis
Peter J
PJ
Percy
Jonathan M
JM