A camphor-derived chiral auxiliary for hydroxyalkyl radicals

Abstract

A new camphor-derived chiral auxiliary for hydroxyalkyl radicals is described. The auxiliary is prepared by the Baeyer–Villiger oxidation of 3-fluorocamphor 12 to give lactone 14, followed by its reduction to the lactol 16. Compound 16 is converted to the acetal–ester 17 and then on to radical precursor 18. A key feature of this auxiliary is the incorporation of a fluorine atom at C-3 (pyranoside numbering), which accelerates the Baeyer–Villiger reaction, results in complete anomeric control during auxiliary attachment, and stabilizes the resulting acetal center. The chiral radical derived from carboxylic acid 18 adds to methyl 2-trifluoroacetoxyacrylate to give adducts 22 and 23 with good diastereocontrol (ds from 3:1 at 0°C up to 4.5:1 at −78°C).