Iterative Organometallic Addition to Chiral Hydroxylated Cyclic Nitrones: Highly Stereoselective Syntheses of α,α'- and α,α-Substituted Hydroxypyrrolidines

Iteration of organometallic addition to chiral hydroxylated pyrroline N-oxides through an addition-oxidation-addition synthetic sequence allowed highly stereoselective double alkylation of pyrrolidine at C-2 or at C-2 and C-5 depending on the regioselectivity of the oxidation step. Application of this methodology has been exemplified by the synthesis of the all-substituted pyrrolidine alkaloid (-)-codonopsinine and of proline-type amino acid precursors possessing a quaternary stereogenic center, whose configuration can be controlled.