@article {46995, title = {Highly enantioselective synthesis of sitagliptin}, journal = {Asian Journal of Organic Chemistry}, volume = {9}, year = {2020}, month = {FEB}, pages = {189-191}, type = {Article}, abstract = {

A highly enantioselective synthesis of sitagliptin, a potent DPP-4 inhibitor, is reported. Explicitly identified chiral FerroLANE ligands in the presence of rhodium catalyze the asymmetric hydrogenation of an enamine to yield sitagliptin with excellent enantioselectivity (98\% ee). The process was scaled up to 5 g and the final product was isolated as a phosphate salt with \>99\% ee.

}, keywords = {asymmetric hydrogenation, catalysis, FerroLANE ligands, Rhodium, sitagliptin}, issn = {2193-5807}, doi = {10.1002/ajoc.201900709, Early Access Date = JAN 2020}, author = {Khopade, V. Kishor and Sen, Anirban and Birajdar, Rajkumar S. and Paulbudhe, Uday P. and Kavale, Dattatry S. and Shinde, Prashant S. and Mhaske, Santosh B. and Chikkali, Samir H.} } @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.} } @article {49335, title = {Thermally stable P-chiral supramolecular phosphines, their self-assembly and implication in Rh-catalyzed asymmetric hydrogenation}, journal = {Chemistry-A European Journal}, volume = {30}, year = {2024}, month = {AUG }, type = {Article}, abstract = {

P-chiral supramolecular phosphine ligands are crucial for asymmetric transformations, but their synthesis is tedious. We report a one-step synthesis of thermally stable P-chiral supramolecular phosphines and their performance in the asymmetric hydrogenation of functionalized alkenes. A rational designing and synthesis of (R, R)-QuinoxP* ligated palladium complex (Pd-2) in excellent yield is reported. This Pd-2 catalyzed a direct P-C coupling of 2,3-dihydro-1-H-phosphindole (A1)/1,2,3,4-tetrahydrophosphindoline (A2) with 1-(3-iodophenyl)urea (B1)/2-iodo /6-hydroxy pyridine (B2) and,produced corresponding ligands L1-L3. The P-C coupling between A1 and B2 produced 6-(2,3-dihydro-1H-phosphindol-1-yl)pyridine-2(1H)-one (L2) with an excellent enantiomeric excess of up to 99 \%. L2 was found to be remarkably stable even at 150 degrees C and did not oxidize/hydrolyze for at least 24 hours in open air. Such thermal stability and an impediment to oxidation are unprecedented. L2 self-assembled and produced L2-C1 (Pt), L2-C2(Pd), and L2-C3(Rh) assemblies. The utility of the self-assembled P-chiral ligand was demonstrated in the Rh-catalyzed asymmetric hydrogenation (AH) of functionalized olefins. The L2-C3 catalyzed AH of functionalized alkenes and delivered chiral products with excellent enantioselectivity of \>99 \%. A small library of 16 substrates was subjected to AH using L2-C3 to produce chiral compounds with excellent conversion and ee.

}, keywords = {asymmetric hydrogenation, Asymmetric phosphination, P-chiral phosphine, Self-assembly, Supramolecular phosphine}, issn = {0947-6539}, doi = {10.1002/chem.202401077}, author = {Chandanshive, Amol C. and Gonnade, Rajesh G. and Chikkali, Samir H.} } @article {49782, title = {Direct synthesis of phosphine-phosphite ligand and its implication in asymmetric hydrogenation of functionalized olefins}, journal = {Chemistryselect}, volume = {11}, year = {2026}, month = {FEB }, pages = {e07548}, type = {Article}, abstract = {

Phosphine-phosphite (P-OP) ligands constitute a privileged class of chiral ligands in asymmetric catalysis owing to their modular structures and tunable steric and electronic properties. Herein, we report a direct, one-pot, synthesis of a new flexible P-OP ligand (L) derived from BINOL-PCl and its in situ complexation with rhodium (Rh) for catalytic evaluation. The resulting Rh/L system efficiently hydrogenates a diverse library of 19 functionalized olefins under mild conditions, delivering moderate to excellent enantioselectivities, with ee values reaching up to 99\%. Several of the hydrogenated products correspond to valuable chiral building blocks relevant to pharmaceutical synthesis, underscoring the practical utility of flexible P-OP ligand architectures in asymmetric hydrogenation.

}, keywords = {asymmetric hydrogenation, functionalized alkene, ligand design, metal catalyzed, phosphine-phosphite}, issn = {2365-6549}, doi = {10.1002/slct.202507548}, author = {Chandanshive, Amol C. and Khopade, Kishor V. and Chikkali, Samir H.} }