Kinetic resolution of aminoalkenes by asymmetric hydroamination: a mechanistic study

The kinetic resolution of chiral aminoalkenes by hydroamination-cyclization was studied by using 3,3'-bis(triarylsilyl)-substituted binaphtholate rare-earth-metal complexes. The resolution of 1-arylaminopentenes proceeds with high efficiency and high trans-diastereoselectivity, whereas the resolution process of 1-alkylaminopentenes suffers from decreasing resolution efficiency with increasing steric demand of the aliphatic substituent. Kinetic studies of the matching and mismatching substrate-catalyst pair by using enantiopure substrates and either the (R)- or (S)-binaphtholate catalysts revealed that the difference in resolution efficiency stems from a shift of the Curtin-Hammett pre-equilibrium. Although 1-arylaminopentenes favor the matching substrate-catalyst complex, preference for the mismatching substrate-catalyst complex for 1-alkylaminopentenes diminishes resolution efficiency. Nevertheless, the relative cyclization rate for the two diastereomeric substrate-catalyst complexes remains in a typical range of 7-10:1. Plausible attractive pi interactions between the aryl substituent and either the metal center or the aromatic system of the bis(triarylsilyl)-substituted binaphtholate ligand may explain increased stability of the matching substrate-catalyst complex. Incidentally, the methoxymethyl (MOM)-substituted aminopentene 3 g also exhibited a strong preference for the matching substrate-catalyst complex, possibly due to the chelating nature of the MOM substituent. The proximity of the stereocenter to the amino group in the aminoalkene substrate was crucial to achieve good kinetic resolution efficiency. The more remote beta-phenyl substituent in 2-phenylpent-4-en-1-amine (5) resulted in diminished discrimination of the substrate enantiomers with respect to the relative rate of cyclization of the two substrate-catalyst complexes and a Curtin-Hammett pre-equilibrium close to unity.