The synthesis of (R)- and (S)-spirobi-1,4-dioxane and related spirobicycles from D-fructose

Abstract

Stereospecific syntheses of (R)- and (S)-spirobi-1,4-dioxane[(19) and (23) respectively] have been achieved starting from 1,2-O-ethylene-β-D-fructopyranose (6) and 2-(β-D-fructopyranosyloxy)ethanol (24) respectively, which are both readily available from 2′-chloroethyl β-D-fructopyranoside. In the former case the triol grouping was cleaved by sodium periodate, and the dialdehyde (7) reduced with sodium borohydride to give the diol (8), which was ring closed to give the (S)-isomer. In the latter case the triol grouping of compound (24) was also cleaved by periodate to give 1,4,7,10-tetraoxaspiro-[5.5]undecane-3,11 -diol which existed as a mixture of 3,11 -epimers (26). Sequential acetylation, treatment with hydrogen bromide–acetic acid, and reduction with lithium aluminium hydride afforded the (R)-isomer. Conversion of the diol (8) into the dimesylate, followed by selective displacement with thioacetate, afforded the monomesylate (18) which on reaction with base afforded (R)-1,7,10-trioxa-4-thiaspiro[5.5]undecane (22). The aza-analogue (20) has been made by a related sequence of reactions.