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One of the major goals of the proposal is to develop methods and catalysts for the enantioselective construction of carbon-halogen bonds (C-X) through addition of halogens and nucleophiles to different substituted alkenes.

We have previously reported that alkynyl substituted olefin underwent regio- and diastereoselective syn-1,4-bromolactonization in the presence of nucleophilic catalysts. DABCO provided the highest diastereoselectivity, generally over 20:1. In the past year, we have developed a bifunctional chiral catalyst that can promote diastereo- and enantioselective syn-1,4-bromolactonization of conjugated (Z)-enynes. The bifunctional catalyst has a urea functional group and a skeleton of cinchona alkaloids. Up to 99% ee was obtained and drs were above 20:1 in most cases. Various substituted bromoallenes were prepared together with lactone heterocycles efficiently and stereoselectively. Our mechanistic studies suggested that the halogenation reagent was activated by the bifunctional catalyst through hydrogen bonding, which is a new type of activation mechanism for halogenation reactions. Further investigation may lead to novel entries for other halogen promoted enantioselective processes.

In the future, we will expand the scope of the halocyclizations to other substituted alkenes and other nucleophiles.