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 pyrrolizid ine alkaloid (+)-xenovenine (2) are described. The strategy involves enanti oselective syntheses of the aminoallene, (SS,8S)-5-amino-trideca-8,9-diene (3), and the aminoallene-alkene, (SS)-5-amino-pentadeca-1,8,9-triene (4), w hich then undergo regio- and stereoselective cyclohydroamination catalyzed by the organolanthanide precatalysts Cp'(2)LnCH(TMS)(2) and Me2SiCp "('BuN) LnN(TMS)(2) (Cp' = eta(5)-Me5C5; Cp " = eta(5)-Me4C5, Ln = lanthanide; TMS = Me3Si). These reactive organolanthanide complexes efficiently mediate hig hly diastereoselective intramolecular hydroamination/cyclization (MC) react ions under mild conditions. The turnover-limiting step in these catalytic c ycles is proposed to be intramolecular insertion into the Ln-N bond of the proximal allenic C=C linkage, followed by rapid protonolytic cleavage of th e resulting Ln-C bond. The rate and selectivity of the insertion process is highly sensitive to the steric demands of the substrate.