Highly Efficient Chiral Spiro Iridium Catalysts And Their Applications In The Hydrogenation Of Ketones

Catalytic asymmetric hydrogenation is one of the most efficient and convenient methods for the preparation of chiral compounds, such as pharmaceuticals and agricultural chemicals. This highly efficient method has received intensive study over the past decades, and a number of highly efficient chiral ligands and catalysts for this transformation have been developed. However, extremely efficient chiral ligands and catalysts are still scarce, and the design and synthesis of new efficient chiral ligands and catalysts continue to be of great importance.In this dissertation, we designed and synthesized a new type of chiral spiro pyridine aminophosphine ligands (abbreviated to SpiroPAPs) bearing a pyridine moiety on the amino group of the ligands based on our developed chiral spiro aminophosphines. And the iridium complexes of SpiroPAPs were successfully used in the hydrogenation of simple ketones andβ-keto esters, and excellent results had been achieved.The SpiroPAP ligands were synthesized from chiral spiro aminophosphines. After reacted with a series of picolinaldehydes in the presence of NaBH(OAc)3 as a reducing reagent, chiral spiro aminophosphines were successfully transferred to SpiroPAPs with excellent yields.In the hydrogenation of simple ketones, the iridium complex of (R)-3i was found to be the most effective chiral catalyst. High enantioselectivities (up to 99.9% ee) and turnover numbers (up to 4,550,000) were obtained for a wide range of aryl alkyl ketones. This represents the best result achieved so far for the catalytic asymmetric hydrogenation of simple ketones.The iridium complex of (R)-3i was also highly efficient for the asymmetric hydrogenation ofβ-keto esters. Under the optimized reaction conditions, a series ofβ-arylβ-keto esters were hydrogenated to the corresponding chiralβ-hydroxy esters in high yields with up to 99.8% ee. The turnover numbers of the hydrogenations was also as high as 930,000. This is the best result achieved to date for the catalytic asymmetric hydrogenation of (3-keto esters.In this dissertation, ten spiro chiral pyridine aminophosphine ligands were synthesized and confirmed by 1H NMR,31P NMR,13C NMR, HRMS analysis. And one iridium complex bearing chiral pyridine aminophosphine ligand was determined by X-ray diffraction analysis.