Synthesis and Herbicidal Activity of [3R,5S,6S]-3-Benzyloxy-5- methoxy-1,7-dioxaspiro[5.5]undecane and...

The synthesis of spiroacetals [3R,5S,6S]-3-benzyloxy-5-methoxy-1,7-dioaxaspiro[5.5]undecane 3 and [3R,5S,6S]-3-methoxy-5-benzyloxy-1,7-dioaxaspiro[5.5]undecane4, where the substituents on the spiroacetal assembly are in a 1,3-diaxial orientation, is described. Epoxidation of unsaturated spiroacetal 5 using dimethyldioxirane showed greater preference for the alpha-epoxide 11 over the beta-epoxide 12. Treatment of the alpha-epoxide 11 with lithium diethylamide in tetrahydrofuran afforded both the allylic alcohol 7 and the homoallylic alcohol 13 in approximately equal amounts. Use of a nonpolar solvent (hexane) suppressed the isomerization of the allylic alcohol 7 to the homoallylic alcohol 13, affording a 21:1 ratio of 7:13. Coordination of an oxygen lone pair with the electron-deficient lithium center of the reagent sets up a transition state in which abstraction of a syn-proton and opening of the epoxide leads to stereoselective formation of allylic alcohol 7 with a pseudoaxial hydroxyl group at C-5. The hydroxyl group liberated in the epoxide rearrangement step was then used to direct a second epoxidation to the lower face of the alkene. Thus, treatment of alcohol 7 with m-CPBA buffered with sodium acetate afforded alpha-syn-epoxy alcohol 9. Subsequent epoxide opening using lithium aluminum hydride proceeded smoothly, affording syn-3,5-diaxial diol 10 and 4,5-diol 22. Epoxy alcohol 9 was then treated with sodium hydride and methyl iodide or benzyl bromide, affording methyl ether 23 or benzyl ether 24, respectively. Reduction of methoxy epoxide 23 with lithium aluminum hydride then afforded alcohol 25 together with the regioisomeric alcohol 27. Benzyloxy epoxide 24 afforded alcohols 29 and 31. Finally benzylation of alcohol 25 afforded bis-ether 3 whereas methylation of alcohol 29 afforded bis-ether 4. Spiroacetals 3 and 4were screened for herbicidal activity and exhibited significant activity against the weeds Avena fatua, Setaria viridis, Amaranthus retroflexus, and Chenopodium album when applied preemergence. Bis-ethers 3 and 4, which contain alkoxy groups anchored in a 1,3-diaxial orientation on a spiroacetal ring, represent the first examples of herbicides based on a spiroacetal ring system.