Asymmetrie Electrophilic Fluorocyclization with Carbon Nucleophiles

摘要

The electrophilic halogenation reaction of olefins coupled with cascade carbocyclization is an iconic biomimetic process for the construction of complex molecules. In 2007, Ishihara and co-workers reported the first example of enantioselective iodocarbocyclization of polyenes with N-iodosuccinimide, a reaction promoted by stoichiometric quantities of a chiral phosphoramidite nucleophile. This system was less effective for bromo- and chlorocarbocyclizations. Indeed, the enantio-purity of the products was significantly lower with N-bromosuccinimide, and the reaction did not proceed in the presence of N-chlorosuccinimide. As a matter of fact, the identification of competent electrophilic halogen sources which allow high-yielding product formation is not trivial, and conceptual advances to control enantioselectivity of these complex processes are in high demand. Since 2007, progress has been slow and in line with the well-recognized challenges associated with halocyclizations involving carbon nucleophiles.