The hydroamination and hydroaminoalkylation are two atom-economical processes for the synthesis of industrially and pharmaceutically valuable amines. In the hydroamination reaction an amine N-H bond is added across an unsaturated carbon-carbon bond, while the hydroaminoalkylation involves the activation of a C-H bond that is located next to an amino group, followed by addition to an unsaturated carbon-carbon bond. Both transformations involve similar substrates and can proceed concurrently.
A particular challenge has been the development of chiral catalysts that can perform these valuable transformations stereo- and chemoselectively.
The Hultzsch group has developed a series of binaphtholate tantalum and niobium complexes that efficiently and selectively catalyze either of these two processes, depending on the nature of the catalyst and substrate used in the transformation. The asymmetric hydroaminoalkylation of N-methylaniline derivatives with simple alkenes can be achieved most efficiently using niobium-based catalysts in enantioselectivities of up to 80% ee. Tantalum complexes on the other hand were shown to facilitate the asymmetric hydroamination/cyclization of aminoalkenes exclusively in up to 81% ee and no hydroaminoalkylation by-products were observed in these reactions.