Organolanthanide-catalyzed hydroamination/cyclization. Efficient allene- based transformations for the syntheses of naturally occurring alkaloids

The total syntheses of the pyrrolidine alkaloid (+)-197B (1) and pyrrolizidine alkaloid (+)-xenovenine (2) are described. The strategy involves enantioselective syntheses of the aminoallene, (5S,8S)-5-amino- trideca-8,9-diene (3), and the aminoallene-alkene, (5S)-5-amino-pentadeca- 1,8,9-triene (4), which then undergo regio- and stereoselective cyclohydroamination catalyzed by the organolanthanide precatalysts Cp'₂LnCH(TMS)₂ and Me₂SiCp''((t)BuN)LnN(TMS)₂ (Cp' = η⁵-Me₅C₅; Cp'' = η⁵-Me₄C₅; Ln = lanthanide; TMS = Me₃Si). These reactive organolanthanide complexes efficiently mediate highly diastereoselective intramolecular hydroamination/cyclization (IHC) reactions under mild conditions. The turnover-limiting step in these catalytic cycles is proposed to be intramolecular insertion into the Ln-N bond of the proximal allenic C=C linkage, followed by rapid protonolytic cleavage of the resulting Ln-C bond. The rate and selectivity of the insertion process is highly sensitive to the steric demands of the substrate.