AmericanChemicalSociety.com

The catalyzed addition of amines to unsaturated carbon-carbon bonds, the so-called hydroamination, offers a waste-free, highly atom-efficient and green pathway to produce nitrogen-containing compounds, such as amines, enamines and imines, which are valuable and industrially important bulk chemicals, specialty chemicals and pharmaceuticals. There have been significant research efforts to develop various transition metal-based catalyst systems (early transition metals of group 3-5 including the lanthanides, actinides, and late transition metals of group 8-12) over the last two decades. This research program primarily aims to develop main group metal-based catalysts with the benefit to utilize significantly less toxic elements for this industrial relevant catalytic transformation. However, significant challenges represent the labile metal-ligand interactions of main group metals; in particular facile Schlenk-type ligand redistribution processes that can potentially thwart efforts to perform enantioselective transformations. An important initial goal was therefore to develop a catalyst system that can resist such ligand exchange processes.

During this funding period Dr. Xiaoming Zhang has successfully investigated a series of magnesium complexes, e.g. 1 and 2, supported by potentially tri- or tetradentate triphenylsilyl-substituted phenoxyamine ligands (Scheme 1).

Scheme 1. Synthesis of triphenylsilyl-substituted aminophenolate magnesium complexes.

Figure 1. ORTEP diagram of the molecular structure of magnesium complex 1.

The X-ray crystallographic analysis of complex 1 confirmed a monomeric structure in which only one of the amine sidearms is bound to the four-coordinate magnesium atom (Figure 1). The free and coordinated sidearms in 1 undergo an exchange process at 25 °C in solution, while the phenoxydiamine complex 2 on the other hand shows no sign of fluxionality. Both complexes were shown to be competent catalysts in the cyclization of aminoalkenes, with complex 1 exhibiting the best catalytic activity (Scheme 2). Both triphenylsilyl-substituted complexes display zero order rate dependence on substrate concentration and first order rate dependence on catalyst concentration. Exchange of the triphenylsilyl substituent in the catalyst by a sterically less shielding tert-butyl group significantly reduced catalytic activity and resulted in a second order rate dependence on substrate concentration. Apparently, the increased steric bulk of the triphenylsilyl substituent ortho to the phenol oxygen in complexes 1 and 2 reduces the risk of ligand redistribution processes via bridging phenolate species and thereby improves catalytic activity. Indeed, no Schlenk-type ligand redistributions were observed and the catalytic active magnesium species was stable after prolonged heating to 120 °C according to a NMR spectroscopic study. Thus, complexes 1 and 2 represent important milestones in our effort to develop environmentally benign chiral alkaline-earth metal-based catalysts for enantioselective hyroamination reactions that allow the atom-economical synthesis of nitrogen-containing fine chemicals and pharmaceuticals.

Scheme 2. Catalytic hydroamination/cyclization of aminoalkenes using an aminophenolate magnesium complex.

Further studies are also aimed to develop catalysts based on heavier alkaline-earth metals, e.g. calcium, which are expected to possess even higher catalytic activity.

In a second approach to main group metal hydroamination catalysts we are investigating the chemistry and catalytic activity of diamidobinaphthyl dilithium complexes as hydroamination catalysts. Preliminary work had shown that proline-modified diamidobinaphthyl dilithium salts are viable catalysts in the hydroamination/cyclization of aminoalkenes at ambient temperatures with high enantiomeric excess (up to 85%; Eq. 1). These preliminary studies suggested that the close proximity and proper geometry of the two lithium atoms plays a pivotal role for good catalyst performance. Catalyst systems lacking the chelating donor arms attached to the diamidobinaphthyl ligand backbone displayed significantly diminished catalytic activity and selectivity. An important aspect of this research program was therefore to investigate the influence of different chelating donor arms on the behavior if this catalyst system.

A number of novel diamidobinaphthyl dilithium complexes incorporating various amino (Figure 2) and ether (not shown) groups in the chelating side arm have been prepared and crystallographically characterized by Lisa Hurd. The structures of theses species significantly depends on the steric demand of the donor functionality. Sterically demanding piperidine or diethylamino groups lead to monomeric diamidobinaphthyl dilithium compounds in the solid state. A slightly reduced steric demand of a dimethylamino group leads to a homochiral dimer in case of the enantiopure complex, while the racemic compound forms an one-of-a-kind heterochiral cyclic hexamer .

Figure 2. Structural diversity in amino-functionalized diamidobinaphthyl dilithium complexes.

Current investigations focus on the structure and aggregation state of these species in solution and their catalytic performance in asymmetric hydroamination reactions. These studies should provide crucial information on the presumably bimetallic reaction mechanism (Scheme 3).

Scheme 3. Proposed bimetallic mechanism for the hydroamination/cyclization of aminoalkenes utilizing diamidobinaphthyl dilithium catalysts.