Synthesis Of Chiral Amines Via Rh-catalyzed Asymmetric Hydrogenation

Chiral amines, which widely exist in natural products and phamarciuticals, are important intermediates and building blocks in organic chemistry. They can be used as chiral auxiliaries, chiral catalysts and drug synthons. Of particular interest for the synthesis of chiral amines is asymmetric hydrogenation for the virtue of high efficiency, atom economy, and cost effectiveness of the methodology. Today, thousands of efficient chiral phosphorus ligands with diverse structures have been developed, and their applications in trasition metal catalyzed asymmetric hydrogenation have been extensively utilized in both academic research and industry. Catalytic enantioselective hydrogenation of dehydroamino acid, enamines and imines with chiral transition metal complexes bearing chiral ligands was found to be one of the most efficient and convenient methods for the preparation of chiral amines and their derivatives. Despite the impressive progress has been achieved in this area, highly enantioselective hydrogenation of some functionalized enamide and unprotected β-enamine acid derivatives remains a challenging task.Herein, rhodium catalyzed asymmetric hydrogenation of three new kinds of substrates was conducted, giving the corresponding chiral amine derivatives in high yields and enantioselecties. The research contents are as follows:1. The highly enantioselective Rh-catalyzed hydrogenation of β-nitro enamide for direct synthesis of enantiomerically pure β-nitro amines, which are versatile precursors in chemical synthesis. Meanwhile, the transformation of β-nitro amine into diamine was conducted by nitro reduction in good yield without loss of enantiopurity.2. Asymmetric hydrogenation of cyclic dienamides catalyzed by Rh-DuanPhos has been developed, which provides a accessible method for the synthesis of chiral cyclic allylic amines in excellent enantioselectivities (up to 99%ee); In the presence of the Crabtree’s catalyst, the product could be further hydrogenated, affording cyclohexane derivatives with high yield and d.r. value. Epoxidation of the hydrogenation product was also performed and then opened the ring by NaN3, affording product with three contiguous stereogenic centers in excellent enantio-and diastereoselectivities (97%ee, dr:>98:2).3. The enantioselective Rh-TaniaPhos catalyzed asymmetric hydrogenation of unprotected β-enamine phosphonates to free β-amino phosphonates with 80%-86%ee and high conversions (>99%conversion). The resulting chiral free β-amino phosphonates and their derivatives are important intermediates in biochemistry and pharmaceuticals.