An organocatalytic strategy for the stereoselective synthesis of C-galactosides with fluorine at the pseudoanomeric carbon

The alpha-fluorination of alpha- and beta-C-ethanals of galactose using Jorgensen catalysts and NFSI was investigated. The crude reaction products were transformed to their primary alcohol or methylenated derivatives, which are versatile precursors to biologically interesting fluorinated glycomimetics. The alpha-C-glycoside substrate gave moderate to high yields of fluorinated alpha-C-glycosides with minor amounts of beta-C-glycoside analogues. The reactions on the beta-C-glycoside were lower yielding but gave exclusively fluorinated beta-C-glycosides. For both alpha-and beta-C-glycoside substrates (R) and (S) catalyst showed complementary stereoselectivity. The preparation of difluorinated materials required the use of racemic catalyst as enantiomerically pure catalyst gave intractable mixtures of products. These results are in line with the results for simple achiral aldehydes, and suggest that stereochemistry in the reactions of these chiral, highly substituted, carbohydrate-derived aldehydes are controlled primarily by the chirality in the catalyst.