C _3-symmetric trisimidazoline-catalyzed enantioselective bromolactonization of internal alkenoic acids

摘要

A method for conducting enantioselective bromolactonization reactions of trisubstituted alkenoic acids, using the C _3-symmetric trisimidazoline 1 and 1,3-dibromo-5,5-dimethyl hydantoin as a bromine source, has been developed. The process generates chiral δ-lactones that contain a quaternary carbon. The results of studies probing geometrically different olefins show that (Z)-olefins rather than (E)-olefins are favorable substrates for the process. The method is not only applicable to acyclic olefin reactants but can also be employed to transform cyclic trisubstituted olefins into chiral spirocyclic lactones. Finally, the synthetic utility of the newly developed process is demonstrated by its application to a concise synthesis of tanikolide, an antifungal marine natural product. A catalytic, enantioselective bromolactonization of internal alkenoic acids has been developed by using C _3-symmetric trisimidazoline (see scheme; DBDMH=1,3-dibromo-5,5- dimethyl hydantoin). Tri- and tetrasubstituted olefinic acids could be applied to give quaternary carbon containing δ-lactones as well as spiro lactones. The synthetic utility of the newly developed process is demonstrated by its application to a concise synthesis of tanikolide.