HYDROXYMETHYLATION OF ALDONOLACTONES AND A CHEMICAL SYNTHESIS OF 3-DEOXY-3-FLUORO-D-FRUCTOSE

(Benzyloxymethyl)lithium, generated in situ from butyllithium and (benzyloxymethyl)tri-n-butylstannane, was found to be an efficient reagent for the monohydroxymethylation of aldono-1,4-lactones to form ketoses. Thus, 4-hydroxy butanoic-1,4-lactone, 2-deoxy-2-fluoro-3,5-di-O-(methoxymethyl)-D- arabinono-1,4-lactone, 2,3,5-tri-O-(methoxymethyl)-D-arabinono-1,4-lactone 5-O-(methoxymethyl)-2,3-O-methylidene-D-ribono-1,4-lactone, 2,3,5,6-tetra-O-(methoxymethyl)-D-altrono-1,4-lactone, 2,3:5,6-di-O-isopropylidene-D-gulono-1,4-lactone and 2,3-O-isopropylidene-L-erythrono-1,4-lactone were respectively converted to 1-benzyloxy-5-hydroxy-2-pentanone, 1-O-benzyl-3-deoxy-3-fluoro-4,6-di-O-(methoxymethyl)-D-fructofuranose, 1-O-benzyl-3,4,6-tri-O-(methoxymethyl)-D-fructofuranose, 1-O-benzyl-6-O-(methoxymethyl)-2,3-O-methylidene-D-psicofuranose, 1-O-benzyl-3,4,6,7-tetra-O-(methoxymethyl)-D- altro-heptulofuranose, 1-O-benzyl-3,4:6, 7-di-O-isopropylidene-D-gulo-heptulofuranose, and 1-O-benzyl-3,4-O-isopropylidene-L-erythro-pentulofuranose in 63-81% yields. By deprotection of 1-O-benzyl-3-deoxy-3-fluoro-4,6-di-O-(methoxymethyl)-D-fructose, 3-deoxy-3-fluoro-D-fructose was prepared for the first time.