Cycloadditions of Nonstabilized 2-Azaallyllithiums (2-Azaallyl Anions) and Azomethine Ylides with Alkenes: [3+2] Approaches to Pyrrolidines and Application to Alkaloid Total Synthesis

The [3+2] cycloaddition of 2-azaallyl anions with alkenes represents an attractive strategy for the synthesis of substituted pyrrolidines. Although cycloadditions of 2-azaallyl anions stabilized by aryl and ester groups have been known for more than three decades, only recently have versions bearing simply hydrogen or alkyl groups been discovered. These nonstabilized 2-azaallyl anions are generated by the low temperature transmetalation of (2-azaallyl)stannanes with alkyllithiums. The resulting nonstabilized 2-azaallyllithiums undergo cycloaddition with certain alkenes and alkynes in both intra- and intermolecular modes to yield pyrrolidine or pyrroline cycloadducts. The methodology has been extended to 2-azapentadienyllithiums, heteroatom-substituted 2-azaallyllithiums, and polymer-supported 2-azaallyllithiums. Asymmetric 2-azaallyl anion cycloadditions have also been investigated. Nonstabilized azomethine ylides may also be generated from (2-azaallyl)stannanes via an N-alkylation/destannylation or N-protonation/ destannylation sequence. Together, the cycloaddition of nonstabilized 2-azaallyllithiums and azomethine ylides with alkenes allows access to a broader range of pyrrolidines, since these species have complimentary reactivity profiles.