@article {47899, title = {Mechanistically guided one pot synthesis of phosphine-phosphite and its implication in asymmetric hydrogenation}, journal = {European Journal of Organic Chemistry}, volume = {2022}, year = {2022}, month = {JAN}, pages = {e202101447}, type = {Article}, abstract = {

Although hybrid bidentate ligands are known to yield highly enantioselective products in asymmetric hydrogenation (AH), synthesis of these ligands is an arduous process. Herein, a one pot, atom-economic synthesis of a hybrid phosphine-phosphite (L1) is reported. After understanding the reactivity difference between an 0-nucleophile versus C-nucleophile, one pot synthesis of Senphos (L1) was achieved (72\%). When L1 was treated with [Rh], P-31 NMR revealed bidentate coordination to Rh. Senphos, in the presence of rhodium, catalyzes the AH of Methyl-2-acetamido-3-phenylacrylate and discloses an unprecedented turn over frequency of 2289, along with excellent enantio-selectivity (92\%). The generality is demonstrated by hydrogenating an array of alkenes. The AH operates under mild conditions of 1-2 bar H-2 pressure, at room temperature. The practical relevance of Ll is demonstrated by scaling-up the reaction to 1 g and by synthesizing DOPA, a drug widely employed for the treatment of Parkinson{\textquoteright}s disease. Computational insights indicate that the R isomer is preferred by 3.8 kcal/mol over the S isomer.

}, keywords = {asymmetric hydrogenation, catalysis, DOPA synthesis, One pot synthesis, Phosphine-phosphite ligand}, issn = {1434-193X}, doi = {10.1002/ejoc.202101447}, author = {Sen, Anirban and Kumar, Rohit and Pandey, Swechchha and Raj, K. Vipin and Kumar, Pawan and Vanka, Kumar and Chikkali, Samir H.} }