The Chemical Catalysis Program supports Professor Adam R. Johnson at Harvey Mudd College who will examine enantioselective hydroamination catalysis and stereoselective polymerization of lactide, which are two areas of significant current interest. The proposed research will examine the hydroamination reaction, which is the addition of a nitrogen-hydrogen bond across a carbon-carbon multiple bond. The highly atom-economical method produces substituted amines that are valuable synthetic targets. A number of metals catalyze this reaction but there are no general methods for it. The asymmetric hydroamination of aminoallenes using titanium complexes of bidentate aminoalcohol ligands gives good regioselectivity, but poor stereoselectivity. The corresponding tantalum complexes have recently been shown to be more stereoselective. The PI and his coworkers will synthesize novel chiral ligands tethered to a chiral amino-alcohol and rapidly screen them, synthesize and study titanium and tantalum complexes with these chiral ligands, and perform catalytic hydroaminations with tethered and untethered ligands. The chiral amino-alcohol complexes will also be used to polymerize the biologically derived monomer, lactide. As a biodegradable polymer based on a renewable feedstock, the development of efficient catalysts for the synthesis of polylactide with varying tacticity is of great importance. If successful, both areas of research will have a transformative impact.
With the support of the Chemical Catalysis Program in the Chemistry Division at the National Science Foundation, Dr. Adam R. Johnson's continued research on hydroamination will have an impact on teaching at the frontiers of organometallic chemistry and will extend to a wide community of inorganic chemistry educators. The results from this research will affect Professor Johnson's teaching of inorganic and organometallic chemistry at Harvey Mudd College and his participation in the NSF-funded VIPEr project (www.ionicviper.org), an on online teaching and networking site for inorganic chemistry. Undergraduate students will have an opportunity to examine modern problems in synthetic organometallic chemistry, synthesize and purify the ligands and complexes, grow crystals, and perform the catalytic reactions. Students will gain experience in creative problem solving and teamwork, and will present their research results both locally and at a national American Chemical Society Meeting.
Hydroamination is the addition of an N-H bond across a carbon-carbon double or triple bond to produce, in our case, a cyclic nitrogen compound that could be potentially useful for pharmaceutical applications. The reaction has high atomic efficiency; every atom in the starting material is conserved in the product. Because the reaction does not occur spontaneously, we require the synthesis of a catalyst to enable the reaction to occur. The catalyst is a metal complex consisting of a titanium or tantalum metal center with a small molecule, called a ligand, attached to it. We design the ligand to affect the selectivity of the reaction. The goal is to achieve the highest enantioselectivity, which means that the catalyst is able to select for one possible isomer over the other by lowering the activation energy of one of the two possible reactions. Previous work has been done by our group using titanium and tantalum metal centers with a wide variety of ligands, more than 30. Trends in our previous data suggest that larger ligands would increase selectivity because larger groups may restrict the movement of the reaction and cause the formation of only one isomer of the final cyclic product. Therefore we aimed to created larger ligands by adding larger groups to our normal starting materials to produce the ligands that we would then attach to the metal. For purification of the ligands we primarily used a column with a solvent system of ethyl acetate, hexanes, and triethylamine. The column was successful in separating naphthalene, which is a common byproduct in our reactions, from the desired product. After carrying out the hydroamination reaction we calculated the enantioselectivity using a technique known as GC-MS. With our new ligands we achieved around 50% enantioselectivity, which is one of our best results. Current work in the laboratory is aimed at changing the shape of the ligand. High level calculations have suggested that if our ligand was a different shape, we would get even higer enantioselectivity.
