Stereocontrolled Synthesis of Highly Substituted Proline Esters via [3 + 2] Cycloaddition between N-Metalated Azomethine Ylides and Nitroalkenes. Origins of the Metal Effect on the Stereochemical Outcome

The [3 + 2] cycloaddition reaction between several N -metalated azomethine ylides and nitroalkenes has been studied using AgOAc and LiClO 4 as metalating reagents in the presence of triethylamine. The reaction is found to be very versatile and can be extended to homochiral nitroalkenes. In general, lithium and silver salts promote preferential formation of the endo and exo cycloadducts, respectively. The presence of a phenol moiety induces a shift toward the exo -cycloadduct even when lithium is used. A model based upon the experimental results obtained and SCF-MO calculations is proposed to explain the variable stereochemical outcome of these reactions.