Novel Chiral P,N Ligands Rong-phos:study On Iridium Catalytic Asymmetric Hydrogenation Reactions

Numerous chiral ligands bearing various coordination groups and skeletons have been developed during the last half century.The application of these ligands in catalytic asymmetric reactions led to significant progress in asymmetric synthesis of natural and pharmaceutical compounds.Central chirality is an important chiral element used in the design of chiral ligands and catalysis.Mostly,the attention of organic chemists is focused on the development of chiral ligands with stable central chiral centers,such as carbon,phosphorus and sulfur.However,the application of N-centered chirality in chiral ligand has been rarely reported due to its flexibility.We demonstrate that the design,synthesis and application of a class of simple P,N-ligands(Rong-Phos)with flexible N-centered chirality and their derived iridium complexes with fixed N-centered chirality.Both fixed configurations of the N-stereogenic center of the iridium complexes could be selectively formed from the same chiral ligand with iridium precursors under different coordination conditions.This pair of diastereoisomeric iridium complexes showed good performance in the enantiodivergent asymmetric hydrogenation of exocyclic ?,?-unsaturated lactams.These results indicate that the chirality of nitrogen center plays an important role in enantio-inducing control.The research contents mainly include the following four parts: 1.The design and synthesis of a new type of chiral P,N ligandsWe developed a new type of chiral P,N ligands(Rong-Phos)with flexible nitrogen-centered chirality.Based on reported works,the Rong-Phos can be easily synthesized in 3 steps in good yields from readily available starting materials.In view of the simple structure,air stability,operational simplicity,and wide structural diversity from readily available starting materials,this type of chiral P,N ligands can be expected to find wide applications in the transition metal catalyzed asymmetric reactions.2.The design and synthesis of the N-Centered Chirality of Iridium ComplexesWe have put forward the concept of N-centered chirality-flexible nitrogen ligands to emphasize the importance of N-centered chirality in the design of chiral ligands.The central chirality of nitrogen could be induced by its inherent carbon chiral center via coordination with iridium.We found a pair of diastereoisomers which have fixed nitrogen-centered chirality of opposite configurations could be formed via switching the coordination conditions.3.Enantio-divergent hydrogenation of Exocyclic ?,?-Unsaturated Lactams Enabled by Switching the N-Centered Chirality of Iridium Complexes.A pair of chiral iridium complexes with opposite nitrogen-centered chirality efficiently catalyzed the asymmetric hydrogenation of exocyclic ?,?-unsaturated lactams,giving corresponding products with opposite configurations with high enantioselectivities.It is the first reported case that the nitrogen-centered chirality controls the configurations of products in enantioselective catalysis.Computational results showed that hydrogen-bonding interaction between N-H of ligand and carbonyl group of the substrate played very important role in the enantio-inducing process.4.Rong-Phos/Iridium(I)-Catalyzed Asymmetric Hydrogenation of Exocyclic ?,?-Alkylidene Carbonyl CompoundsCyclic carbonyl compounds with ?-chiral carbon centers are of great interest in pharmaceutical sciences and asymmetric synthesis.A new type of chiral iridium complexes were prepared and they were able to successfully hydrogenate the challenging six-and seven-membered ?-alkylidene carbonyls with excellent enantioselectivities.The excellent catalytic performance was also extended to the hydrogenation of some other mediumsized cyclic ?,?-unsaturated carbonyls.