Naturally occurring cinchona alkaloids include quinine, quinidine, cinchonine, and cinchonidine. Many of their derivatives are also readily available. This Focus Review summarizes recent applications of cinchona alkaloid derivatives, an important class of organocatalysts, in enantioselective halofunctionalization of alkenes and alkynes. Most successful examples in this area are intramolecular halofunctionalizations, where the nucleophile is tethered with the alkene or alkyne substrate. Only a few catalytic enantioselective intermolecular halofunctionalization of alkenes have been realized. Dimeric cinchona alkaloids are the most frequently used catalysts in asymmetric halofunctionalizations. Most other catalysts have an appended functional group on the C9 position of the cinchona alkaloids. These functional groups include (thio)urea, thiocarbamate, and sulfonamides.

Halocyclization of alkenes was realized using N-acylhemiaminal nucleophiles. High diastereoselectivity could be achieved for the formation of three stereogenic centers in this halogen-mediated cyclization reaction. We also demonstrated that enantioselective bromocyclization of alkenes using N-acylhemiaminal nucleophiles was possible. Chirality 25:805–809, 2013. © 2013 Wiley Periodicals, Inc.

New organocatalysts have been developed for the enantioselective halolactonization of (Z)-1,3-enynes and 1,1-disubstituted alkenes. In the case of 1,3-enynes, the carboxylate nucleophile and halogen electrophile were added to the conjugated π-system from the same face. Up to 99 % ee was achieved for the 1,4-syn-bromolactonization of conjugated (Z)-1,3-enynes. Based on the results from the enyne halolactonization, a second generation of catalysts was designed for simple olefins. Up to 91 % ee was observed for chlorolactonization of 1,1-disubstituted alkenes. The catalysts developed for the enantioselective halolactonization of both enynes and alkenes are composed of a cinchona alkaloid skeleton tethered to a urea group.