Through independent research and development and technical know-how accumulation, Bellen has mastered metal catalysis and ligand screening technology, and established a catalyst and ligand library to screen the best catalysts and ligands for carbon-carbon, carbon-oxygen and carbon-nitrogen coupling reactions, including high-pressure asymmetric hydrogenation reaction catalytic screening and catalytic coupling reaction. We continue to enrich the number of catalysts and ligands for various reactions, accumulate practical experiences, and have widely applied metal catalysis and ligand screening technology to the process development of customers' drug molecules. Some cases are listed as follows:

• Asymmetric reduction reaction: In the process development of a drug synthesis, the Rh-catalyzed asymmetric reduction double bond reaction was used to construct β-methyl-α-phenylalanine, achieved high stereospecific ivity, and loading was reduced from the initial 2% to 0.2% by screening the catalyst equivalents, effectively reduced overall project cost.
• Suzuki-Miyaura cross-coupling reaction: In the process development of an intermediate for a new drug, through the screening of palladium catalysts (6 types of zero-valent palladium and 18 types of divalent palladium) and ligands (150 types of ligands), the technical team successfully overcame various problems in the original process, including dehalogenation, poor stability, low yield, and low production efficiency due to column chromatography, and increased the yield from 36% to over 90%, improved production efficiency and reduced raw material cost.
• Noyori asymmetric hydrogenation reaction: In the process development of a small molecule drug target compound, we achieved asymmetric reduction of cyclic β-ketoacids by Noyori asymmetric hydrogenation reaction and successfully achieved steric control of two chiral centers simultaneously by asymmetric reduction and dynamic thermodynamic principles. In this process, the optimal combination was found by high throughput of Ru catalysts and ligand screening, which finally avoided the expensive SFC separation that had to be used in the original process and improved yield by 200%, greatly reduced manufacturing cost and improved efficiency.