Cycloadditive Reactions

Heterocycles are routinely encountered as structural units of biologically active unnatural and natural organic compounds. The contemporary chemist has at his or her disposal myriad modern methods to synthesize heterocyclic structures, yet the time-honored cycloaddition reaction between an olefin and reactive 1,3-dipoles is central because of its chemical efficiency and the breadth of structures accessible.

Researchers in the Johnson Group, in collaboration with scientists from the Synthetic Organic Chemistry Laboratory, RIKEN Center for Sustainable Resource Science, and RIKEN Center for Emergent Matter Science, as published in JACS, have developed an enantioselective [3 + 2] cycloaddition reaction between nitrile oxides and transiently generated enolates of α-keto esters. The catalyst system was found to be compatible with in situ nitrile oxide-generation conditions.

A versatile array of nitrile oxides and α-keto esters could participate in the cycloaddition, providing novel 5-hydroxy-2-isoxazolines in high chemical yield with high levels of diastereo- and enantioselectivity. Notably, the optimal reaction conditions circumvented concurrent reactions via O-imidoylation and hetero-[3 + 2] pathways.

With the above data in hand, the Johnson Group researchers are currently assessing the reactivity of the 5-hydroxy-2-isoxazolines in other downstream transformations in addition to studying the mechanism of this transformation in detail. These results will be highlighted here in due course.