Synthesis of exo-methylenedifluorocyclopentanes as precursors of fluorinated carbasugars by 5-exo-dig radical cyclization

The synthesis of polyhydroxylated 1,1-difluoro-5-methylenecyclopentanes is described. The sequence involves an addition of PhSeCF2TMS to a tartrate-derived aldehyde or its corresponding tert-butanesulfinylimines followed by a radical cyclization. The use of a benzyl protected substrate led to an unproductive 1,5-hydrogen transfer after cyclization but the desired compound was eventually obtained from the unprotected substrate. A hydroboration/oxidation sequence was investigated on these 1,1-difluoro-5-methylenecyclopentanes as it would provide fluorinated carbasugars, a new and promising class of glycomimetics. Unfortunately, this reaction was poorly efficient and its regioselectivity not the expected one.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► An addition of PhSeCF2TMS to ynals or ynimines provides a radical precursor. ► The 5-exo-dig cyclization affords precursors of fluorinated carbasugars. ► The hydroboration of the methylenecyclopentane is unproductive.