A New Modular Phosphite‐Pyridine Ligand Library for Asymmetric Pd‐Catalyzed Allylic Substitution Reactions: A Study of the Key Pd‐π‐Allyl Intermediates

Abstract

A library of phosphite-pyridine ligands L1-L12 a-g has been successfully applied for the first time in the Pd-catalyzed allylic substitution reactions of several di- and trisubstituted substrates by using a wide range of C, N and O nucleophiles, among which are the little studied α-substituted malonates, β-diketones, and alkyl alcohols. The highly modular nature of this ligand library enables the substituents/configuration at the ligand backbone, and the substituents/configurations at the biaryl phosphite moiety to be easily and systematically varied. We found that the introduction of an enantiopure biaryl phosphite moiety played an essential role in increasing the versatility of the Pd-catalytic systems. Enantioselectivities were therefore high for several hindered and unhindered di- and trisubstituted substrates by using a wide range of C, N and O nucleophiles. Of particular note were the high enantioselectivities (up to>99% ee) and high activities obtained for the trisubstituted substrates S6 and S7, which compare favorably with the best that have been reported in the literature. We have also extended the use of these new catalytic systems in alternative environmentally friendly solvents such as propylene carbonate and ionic liquids. Studies on the Pd-π-allyl intermediates provide a deeper understanding of the effect of ligand parameters on the origin of enantioselectivity.

Adaptable P–X Biaryl Phosphite/Phosphoroamidite‐Containing Ligands for Asymmetric Hydrogenation and C–X Bond‐Forming Reactions: Ligand Libraries with Exceptionally Wide Substrate Scope

“…We next decided to take one further step in the design of new ligand libraries using phosphite–pyridines L36 – L47 12 and phosphite–amine L48 – L53 13 ligand libraries (Figure ), which incorporated the advantages of the heterodonor, the robustness of the pyridine/amine moieties, and the extra control provided by the flexibility of the chiral pocket through the presence of a biaryl phosphite group.…”

“…We next decided to synthesize and screen a library of 84 potential new phosphite–pyridine ligands ( L36 – L47c – g , j – k ; Figure ) 12a. These ligands incorporate the advantages of the heterodonor, the robustness of the pyridine moiety, and the extra control of the chiral pocket through the presence of biaryl phosphite groups.…”

“…By a systematic variation of the substituents at the ligand backbone (R 1 and R 2 , ligands L36 – L42 ), the configuration of the carbon next to the phosphite moiety (ligands L36 – L42 vs. L44 – L47 ), and the substituents and configurations in the biaryl phosphite moiety ( c – g , j – k ), we could achieve high enantioselectivities and activities in several di‐ and trisubstituted substrates by using a wide range of C‐, N‐ and O‐nucleophiles, including the less studied α‐substituted malonates, β‐diketones and alkyl alcohols (Figure ). 12a…”

Comparative Study of Novel Phosphordiamidite and Phosphite Ligands Used in Alkene Hydroformylation; Synthesis, Characterization, Metalation, and Catalytic Evaluation

“…To expand upon this research, it is of interest to incorporate other donating groups that can act as hemilabile ligands such as pyridyl groups . Similar heterodonor P,N ligand have been used successfully in Pd‐catalyzd Suzuiki–Miyayra coupling, asymmetric Pd‐catalyzed allylic alkylation reactions, Cu‐catalyzed asymmetric conjugate 1,4‐additions, and Ir‐ or Rh‐catalyzed alkene hydrogenations,, , but very few have been studied in Rh‐catalyzed hydroformylation reactions . These catalysts are more complicated than the mixed P‐donor/ether ligands that we previously studied because the pyridyl group is more likely to competitively bind to the catalytically active Rh I metal centers .…”

Development of a Novel Multifunctional N,P Ligand for Highly Enantioselective Palladium‐Catalyzed Asymmetric Allylic Etherification of Alcohols and Silanols

“…[4a, 6] Notably, in 2008, Chan and co-workers reported a palladium-catalyzed asymmetric allylic etherification of 1,3-diphenyl-2-propenyl acetate with alcohols in moderate to high yields (58-98 %) and good to excellent levels of enantioselectivity (83-96 %ee) by using the (S, p R)-FerroNPS ligand. [7] Meanwhile, the research groups of Hou, Ding, Fukuzawa, Du, and others [8] have also demonstrated independently that various bidentate phosphine or phosphite ligands associated with palladium centers afford chiral allylic ethers in moderate to good levels of enantioselectivity and diastereoselectivity. However, this useful process to provide chiral allylic ethers still needs substantial improvement in its level of enantioselectivity and chemical yield to be more practical.…”