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, (5 S,8 S )-5-amino-trideca-8,9-diene ( 3 ), and the aminoallene-alkene, (5 S )-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‘ ‘( t BuN)LnN(TMS) 2 (Cp‘ = η 5 -Me 5 C 5; Cp‘ ‘ = η 5 -Me 4 C 5; Ln = lanthanide; TMS = Me 3 Si). 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.