Brian Connell and colleagues at Texas A&M University observed that reactive nitrones can be generated in situ by an unusual reaction of nitrosobenzene with styrene. The nitrone formed then undergoes a 1,3-dipolar cycloaddition with the excess styrene as the dipolarophile to provide the desired isoxazolidine in moderate to good yields.
Connell also demonstrated the versatility of the reaction by trapping the reactive in situ nitrone with dipolarophiles that are more reactive than styrene to generate a library of isoazolidines containing different substituents at the 2- and 5-positions. Isoxazolidine moieties are often used in the synthesis of complex molecules and/or present in biologically active compounds.
In the future, Connell hopes to develop an enantioselective version of this reaction which would have many potentially useful applications.
Original publication: Jun Yong Kang, Alejandro Bugarin and Brian T. Connell, Chem. Commun., 2008