Highly stereoselective intramolecular hydroamination/cyclization of conjugated aminodienes catalyzed by organolanthanides

Efficient intramolecular hydroamination/cyclization of primary and secondary conjugated aminodienes can be effected by using organolanthanide precatalysts of the type Cp-₂LnCH(TMS)₂ (Cp- = η⁵-Me₅C₅; Ln = La, Sm, Y; TMS = SiMe₃) and CGCSmN(TMS)₂ (CGC = Me₂Si(η⁵-Me₄C₅)(^tBuN)). The transformation proceeds cleanly (≥ 90% conversion) at 25-60 °C with good rates and high regioselectivities, and with electronic effects leading to significant rate enhancements. Some features of the reaction parallel monosubstituted aminoalkene hydroamination/cyclization, including rate law (zero order in [aminodiene]), and rate enhancements observed with larger lanthanide ionic radii and/or more open catalyst ligation structures. Good to excellent diastereoselectivity is obtained in the synthesis of 2,5-trans-disubstituted pyrrolidines (80% de) and 2,6-cis-disubstituted piperidines (99% de) with using the corresponding α-methyl aminodiene precursors. Formation of 2-(prop-1-enyl)piperidine with the chiral C1-symmetric precatalyst (S)-Me₂Si(OHF)(CpR*)SmN(TMS)₂ (OHF = η⁵-octahydrofluorenyl; Cp = η⁵-C₅H₃; R* = (-)-menthyl) proceeds with up to 69% ee.