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, (SS,8S)-5-amino-trideca-8,9-diene (3), and the aminoallene-alkene, (SS)-5-amino-pentadeca-1,8,9-triene (4), which then undergo regio- and stereoselective cyclohydroamination catalyzed by the organolanthanide precatalysts Cp'(2)LnCH(TMS)(2) and Me(2)SiCp "('BuN)LnN(TMS)(2) (Cp' = eta(5)-Me(5)C(5); Cp " = eta(5)-Me(4)C(5), Ln = lanthanide; TMS = Me(3)Si). These reactive organolanthanide complexes efficiently mediate highly diastereoselective intramolecular hydroamination/cyclization (MC) 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.