Synthesis of novel chiral P-Phos derivative for asymmetric catalysis and development of air-stable and recyclable chiral catalyst systems

Abstract

The air-stable Ir/(R)-P-Phos/THF system for asymmetric hydrogenation of a variety of quinolines has been investigated and 2-methyl quinoline shows the highest ee value of 91%. This catalyst system can give the same results without using glovebox and degased THF. The Ir/(R)-P-Phos and Ir/(R)-MeO-BIPHEP catalysts can also be immobilized in polyethylene glycol dimethyl ether (MW = 500) for the effective asymmetric hydrogenation of 2-methyl quinoline over 5 cycles with ee up to 86% and 84%, respectively, and the operation can be carried out with non-degased hexane and without the use of glovebox. The air sensitive Ir/(R)-BINAPO/THF and Ir/(S)-H8-BINAPO/THF systems can also be applied for asymmetric hydrogenation of quinolines with high ee value. In addition, Ir/(R)-BINAPO and Ir/(S)-H8-BINAPO catalyst systems can be immobilized in polyethylene glycol dimethyl ether (MW = 500) for effective asymmetric hydrogenation of 2-methyl quinoline with similar enantioselectivities. However, the results on recycling are not satisfactory. We have also extended the application of Ru(R-P-Phos)Cl2(DMF)n catalyst in room temperature ionic liquids (BMImBF4 and BMImPF6) with methanol as co-solvent for asymmetric hydrogenation of alpha keto-esters with enantioselectivities up to 93% while for beta keto-esters with enantioselectivities up to 99%. Finally, a new chiral ortho phenyl substituted P-Phos (2,2',6,6'-tetramethoxy-5,5'-diphenyl-4,4'-bis(diphenylphosphino)-3,3'-bipyridine, o-Ph-P-Phos) has been synthesized and its application in asymmetric catalysis has been investigated in comparison with P-Phos. The results show that the phenyl ring at the ortho position have significant effect on the enantioselectivity of the asymmetric catalysis. The catalytic reactions included (1) iridium catalyzed asymmetric hydrogenation of 2-methyl quinoline with 37% ee (91% ee for P-Phos); (2) palladium catalyzed asymmetric allylic substitution of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate with 16% ee (78% for P-Phos); (3) rhodium catalyzed asymmetric hydrogenation of enamides with o-Ph-P-Phos performs better than P-Phos with ee up to 65%; and, (4) asymmetric hydrogenation of beta enamidophosphonate with 15% ee while no expected conversion was detected by using P-Phos. The result of MM2 calculation shows that the torsion angle for the new ligand is 85o while for P-Phos is 75o.