Etherification of Functionalized Phenols with Chloroheteroarenes at Low Palladium Loading: Theoretical Assessment of the Role of Triphosphane Ligands in CO Reductive Elimination

Abstract

The present study highlights the potential of robust tridentate ferrocenylphosphanes with controlled conformation as catalytic auxiliaries in C À O bond formation reactions. Air-stable palladium triphosphane systems are efficient for selective heteroaryl ether synthesis by using as little as 0.2 mol% of catalyst. These findings represent an economically attractive and clean etherification of functionalized phenols, electron-rich, electron-poor and para-, metaor ortho-substituted substrates, with heteroaryl chlorides, including pyridines, hydroxylated pyridine, pyrimidines and thiazole. The etherification tolerates very important functions in various positions, such as cyano, methoxy, amino, and fluoro groups, which is useful to synthesize bioactive molecules. DFT studies furthermore demonstrate that triphosphane ligands open up various new pathways for the C À O reductive elimination involving the third phosphane group. In particular, the rate for one of these new pathways is calculated to be about 1000 times faster than for reductive elimination from a complex with a similar ferrocenyl ligand, but without a phosphane group on the bottom Cp-ring. Coordination of the third phosphane group to the palladium(II) center is calculated to stabilize the transition state in this new pathway, thereby enhancing the reductive elimination rate.

Hexaphosphine: A Multifaceted Ligand for Transition Metal Coordination

“…[35] Cationic palladium complex5, [{Pd(η 3allyl)} 2 1][FeCl 4 ], was obtained from a mixture of 1 (10.2 mg, 7.90 ϫ 10 -3 mmol) and [{PdCl(η 3 -allyl)} 2 ] (3.0 mg, 8.20 ϫ 10 -3 mmol) in the presence of an excess of FeCl 2 solvated in dichloromethane (1.…”

Thioetherification of Chloroheteroarenes: A Binuclear Catalyst Promotes Wide Scope and High Functional‐Group Tolerance

“…In recent studies, high TONs have been reported for a range of coupling reactions that have used ferrocenylpolyphosphane supporting ligands. By combining the robustness and air tolerance of the ferrocene platform with the polydentate chelating properties of the phosphorus donors,19 palladium‐catalyzed CC cross‐couplings reactions,20 the direct CH functionalization of heteroaromatic compounds,21 and CO bond formation have been successful 22. We examined their performance for the CS coupling of heteroarylchlorides with functionalized thiophenols, which have remained underexplored substrates.…”

Amine, Phenol, Alcohol, and Thiol Arylation

“…In 2011, Platon et al reported -in an experimental-theoretical paper -on the etherification of functionalized phenols (containing cyano, methoxy, amino, and fluoro groups) with chloroheteroarenes and air-stable palladium triphosphane systems at a loading as low as 0.2 mol% [70]. Palladium allyl chloride dimer complex was used as the precatalyst.…”

“…15 The best-performing ligands in the fenol arylation study byPlaton et al [70a] 16. The arylation of triazol-1-yloxy and triazol-1-yl heterocycles with aryl boronic acids by a group at Wyeth[70].…”