Transition-Metal-Catalyzed Transformation of Sulfonates via S–O Bond Cleavage: Synthesis of Alkyl Aryl Ether and Diaryl Ether

Abstract

The catalytic conversion of sulfonates, a versatile class of pharmaceutical intermediates, is usually based on C−O bond cleavage. In this paper, however, we discover a rare transformation of sulfonates via S−O bond cleavage catalyzed by transition metal, through which alkyl sulfonates could undergo an intramolecular desulfitative C−O coupling to form aryl alkyl ethers in the presence of a nickel catalyst. Meanwhile, aryl sulfonates perform similarly to give diaryl ethers catalyzed by a palladium complex. This transformation could tolerate a wide range of functionalities. Controlled experiments reveal that the 2-pyridyl group is necessary to promote the reaction as designed. Crossover experiments proved that this transformation might proceed partly in an intermolecular pathway.

Ni-catalyzed C–S bond construction and cleavage

“…104 In 2019, Lian's research group used a nickel-catalyzed system to achieve the intramolecular removal of SO 2 from 2-pyridyl sulfonate for the preparation of a series of 2-pyridyl alkyl ethers. 105 In this reaction, the cleavage of the S-O bond was catalyzed by nickel, and the aryl alkyl ether was obtained by reductive elimination. Notably, this method could also be applied to Pd catalysts.…”

Nickel-Catalyzed Intramolecular Desulfitative C—N Coupling: A Synthesis of Aromatic Amines

“…Subsequently, Yorimitsu and Wei both independently reported nickel-catalyzed intramolecular CC coupling reactions of sulfones via SO 2 extrusion . Recently, we reported both nickel- and palladium-catalyzed intramolecular desulfitative CO couplings of sulfonates . Despite these efforts, there are still no examples of transition metal-catalyzed intramolecular CN bond forming reactions by SO 2 extrusion .…”

“…11 Recently, we reported both nickel-and palladium-catalyzed intramolecular desulfitative CO couplings of sulfonates. 12 Despite these efforts, there are still no examples of transition metal-catalyzed intramolecular CN bond forming reactions by SO 2 extrusion. 13 Herein, we report the first example of such a transformation.…”

“…Inspired by many of the inter- and intramolecular desulfitative coupling reactions, we initiated our study with a substrate containing a pyridyl group as a potential directing group. − Importantly, pyridines are pivotal in medicinal chemistry. Our initial investigation employed 4-(pyridin-2-ylsulfonyl)­morpholine ( 1a ) as the substrate, 10 mol % Ni­(COD) 2 as the catalyst, 1.5 equiv of KO t Bu as the base, and xylene as the solvent at 140 °C (Table ).…”

Sulfone-Mediated SNAr Reaction as a Powerful Tool for the Synthesis of 4-Quinolinyl Ethers and More—Application to the Synthesis of HCV NS3/4a Protease Inhibitor BI 201420

“…The S N Ar reaction of 4-chloroquinoline with alcohol is usually sluggish, especially when reacting with 2° or 3° alcohol, and byproducts are produced significantly under harsh conditions. Transition-metal-catalyzed aryl ether formation has been a rapidly developing area in recent years, , but application to 4-quinoline ethers has been very rare, probably partly because quinoline-promoted ligand exchange can destroy some catalyst complexes. So far, the most frequently employed method in drug discovery is via alkylation of 4-hydroxyquinolines (S N 2 approach, Scheme ), but it has the following limitation and drawbacks.…”