A Modified Williamson Synthesis And Its Application In Organic Synthesis

This dissertation focused on providing an eiffcient method for construction ofcyclic ether via a modified Williamson ether synthesis. Using monoprotected diols asstarting mateiral, the naked hydroxyl was activated to attack the protected hydroxyl toconstruct a cyclic ether in one step. This method has the benefit of highly selectivityof protecting group strategy and avoids the removal of the protecting group.This strategy provided an effective method for diversity oriented synthesis ofandrostane with6，19-O-bridge. These compounds can supply meterials for furtherbioactivity test.In the first part, we prepared reaction substance from easily available rawmaterial. We screened activating agents, reaction solvents and bases to find out bestreaction condition： RfSC^F as activating agent,MeCN as solvent and DBU asbase,and the yield is up to98%.In the second part, using our method, we synthesis(R)-19-methyl-6(3,19-epoxyandrost-4-ene-3,17-dione in41%atfer9steps from6p-methoxymethoxy-19-hydroxyl-4-androstene-3,17-dione, and we found that thisreaction has excellent selectivity to provide stereospecifically(R)-19-methyl-6p,19-epoxyandrost-4-ene-3,17-dione.