| We have discovered that organolanthanide complexes of the general type Cp′2LnCH(TMS)2 (Cp′ = η5-Me5C5; Ln = La, Sm, Y, Lu; TMS = SiMe3) serve as effective precatalysts for the rapid, regioselective, and highly diastereoselective intramolecular hydroamination/cyclization (IHC) of aminoallenes having the general formula RCH=C=CH-(CH2) n-CHR′NH2 to yield the corresponding heterocycles (R = CH3, n-C3H 7, n-C5H11; R′ = H, CH3, n-C4H9, CH 2=CHCH2CH2). The mono- and disubstituted pyrrolidines and piperidines produced bear an α-alkene functionality available for further synthetic manipulations. Kinetic and mechanistic data parallel organolanthanide-mediated intramolecular aminoalkene and aminoalkyne hydroamination/cyclization. The reaction rate is zero-order in [aminoallene] and first-order in [catalyst] over three or more half-lives. The turnover-limiting step is proposed to be the intramolecular insertion of the proximal allenic C=C bond into the Ln-N followed by rapid protonolysis of the resulting Ln-C bond.; We accomplished the total asymmetric syntheses of the pyrrolidine alkaloid (+)-197B and pyrrolizidine alkaloid (+)-Xenovenine using the aforementioned precatalysts, and the novel organolanthanide complexes Me2SiCp ″(tBuN)LnN(TMS)2 (Cp′ = η5-Me5C5; Cp″ = η5-Me4C5; Ln = Sm, Y; TMS = Me3Si). The strategy involves enantioselective syntheses of the aminoallene, (5S,8S)-5-amino-trideca-8,9-diene, and the aminoallene-alkene, (5S)-5-amino-pentadeca-1,8,9-triene, which then undergo regio- and stereoselective cyclohydroamination reaction. The rate and selectivity of the insertion process is highly sensitive to the steric demands of the substrate. |
