Asymmetric Hydroamination

Amine synthesis is industrially important, from the energy-intensive but highly impactful production of ammonia, to pharmaceutical molecules. Commercial amine manufacturing often involves multistep processes to build C–N bonds, whereas the addition reaction of amines and olefins can provide new amines in a single step. Additional efficiencies may be realized with control over proximal or vicinal stereocenters. A number of challenges face hydroamination catalysis, both in terms of understanding mechanism of highly efficient catalysts and developing new stereocontrol.

ToRM-based Catalysts

ToTMgMe
ToTMgMe

We have studied a steries of oxazoline-based catalysts for the hydroamination of aminoalkene, using group 2 element-, rare earth element-, and group 4 metal-based catalysts. Monoanionic tris(oxazolinyl)borate ligands, such as ToM and ToT, give catalytically active group 2 catalysts. Through kinetic studies, the magnesium catalyst ToMMgMe provides a key mechanistic insight that two equivalents of aminoalkene for cyclization. Catalytic activity decreases with rare earth element-based ToMY(CH2SiMe3)2THF, and the group 4 complex ToMZr(NMe2)3 does not show catalytic conversion.

{PhB(OxR)2Cp}M-based Catalysts

{PhB(OxMe2)2Cp}Zr(NMe2)2
{PhB(OxMe2)2Cp}Zr(NMe2)2

Substitution of one oxazoline in the tris(oxazolinyl)borate ligands with a C5H4 group gives the dianionic ligand class {PhB(OxR)2Cp}. Catalysts supported by these ligands show a number of interesting features. Zirconium compounds catalyze hydroamination at room temperature and even down to -30 °C. Optically active derivatives, such as {PhB(OxiPr,Me2)2Cp}Zr(NMe2)2 provide five membered and seven membered cyclic amines with high enantioselectivity (up to 99%!) Interestingly, deuterium-substituted aminoalkenes (D2NR) undergo hydroamination with higher enantioselectivity than the unlabeled isotopomers (H2NR). Remarkably, the yttrium-based catalyst {PhB(OxtBu)2Cp}Y(CH2SiMe3)2 gives the mirror image product from the zirconium catalyst {PhB(OxtBu)2Cp}Zr(NMe2)2 supported by the identical ligand!