Nickel- and Palladium-Catalyzed Coupling of Aryl Fluorosulfonates with Aryl Boronic Acids Enabled by Sulfuryl Fluoride

Herein are reported examples of the nickel- and palladium-catalyzed cross-coupling of aryl fluorosulfonates and aryl boronic acids. These reactions occur in good to excellent yields under mild conditions with excellent functional group compatibility employing either Pd­(OAc)₂ and inexpensive PPh₃ or the inexpensive and readily available NiCl₂(PCy₃)₂. Importantly, the in situ conversion of phenol derivatives to the corresponding aryl fluorosulfonate by reaction with sulfuryl fluoride and a base and subsequent cross-coupling to form biaryls in a single pot are described. The combination of inexpensive sulfuryl fluoride and efficient catalysts reported in these methodologies will enable economical Suzuki coupling of phenols in pharmaceutical and agrochemical processes

Reductive Elimination from Phosphine-Ligated Alkylpalladium(II) Amido Complexes To Form sp³ Carbon–Nitrogen Bonds

We report the formation of phosphine-ligated alkylpalladium­(II) amido complexes that undergo reductive elimination to form alkyl-nitrogen bonds and a combined experimental and computational investigation of the factors controlling the rates of these reactions. The free-energy barriers to reductive elimination from <i>t</i>-Bu₃P-ligated complexes were significantly lower (ca. 3 kcal/mol) than those previously reported from NHC-ligated complexes. The rates of reactions from complexes containing a series of electronically and sterically varied anilido ligands showed that the reductive elimination is slower from complexes of less electron-rich or more sterically hindered anilido ligands than from those containing more electron-rich and less hindered anilido ligands. Reductive elimination of alkylamines also occurred from complexes bearing bidentate P,O ligands. The rates of reactions of these four-coordinate complexes were slower than those for reactions of the three-coordinate, <i>t</i>-Bu₃P-ligated complexes. The calculated pathway for reductive elimination from rigid, 2-methoxyarylphosphine-ligated complexes does not involve initial dissociation of the oxygen. Instead, reductive elimination is calculated to occur directly from the four-coordinate complex in concert with a lengthening of the Pd–O bond. To investigate this effect experimentally, a four-coordinate Pd­(II) anilido complex containing a flexible, aliphatic linker between the P and O atoms was synthesized. Reductive elimination from this complex was faster than that from the analogous complex containing the more rigid, aryl linker. The flexible linker enables full dissociation of the ether ligand during reductive elimination, leading to the faster reaction of this complex

Reductive Elimination from Phosphine-Ligated Alkylpalladium(II) Amido Complexes To Form sp³ Carbon–Nitrogen Bonds

We report the formation of phosphine-ligated alkylpalladium­(II) amido complexes that undergo reductive elimination to form alkyl-nitrogen bonds and a combined experimental and computational investigation of the factors controlling the rates of these reactions. The free-energy barriers to reductive elimination from <i>t</i>-Bu₃P-ligated complexes were significantly lower (ca. 3 kcal/mol) than those previously reported from NHC-ligated complexes. The rates of reactions from complexes containing a series of electronically and sterically varied anilido ligands showed that the reductive elimination is slower from complexes of less electron-rich or more sterically hindered anilido ligands than from those containing more electron-rich and less hindered anilido ligands. Reductive elimination of alkylamines also occurred from complexes bearing bidentate P,O ligands. The rates of reactions of these four-coordinate complexes were slower than those for reactions of the three-coordinate, <i>t</i>-Bu₃P-ligated complexes. The calculated pathway for reductive elimination from rigid, 2-methoxyarylphosphine-ligated complexes does not involve initial dissociation of the oxygen. Instead, reductive elimination is calculated to occur directly from the four-coordinate complex in concert with a lengthening of the Pd–O bond. To investigate this effect experimentally, a four-coordinate Pd­(II) anilido complex containing a flexible, aliphatic linker between the P and O atoms was synthesized. Reductive elimination from this complex was faster than that from the analogous complex containing the more rigid, aryl linker. The flexible linker enables full dissociation of the ether ligand during reductive elimination, leading to the faster reaction of this complex

Reductive Elimination from Phosphine-Ligated Alkylpalladium(II) Amido Complexes To Form sp³ Carbon–Nitrogen Bonds

We report the formation of phosphine-ligated alkylpalladium­(II) amido complexes that undergo reductive elimination to form alkyl-nitrogen bonds and a combined experimental and computational investigation of the factors controlling the rates of these reactions. The free-energy barriers to reductive elimination from <i>t</i>-Bu₃P-ligated complexes were significantly lower (ca. 3 kcal/mol) than those previously reported from NHC-ligated complexes. The rates of reactions from complexes containing a series of electronically and sterically varied anilido ligands showed that the reductive elimination is slower from complexes of less electron-rich or more sterically hindered anilido ligands than from those containing more electron-rich and less hindered anilido ligands. Reductive elimination of alkylamines also occurred from complexes bearing bidentate P,O ligands. The rates of reactions of these four-coordinate complexes were slower than those for reactions of the three-coordinate, <i>t</i>-Bu₃P-ligated complexes. The calculated pathway for reductive elimination from rigid, 2-methoxyarylphosphine-ligated complexes does not involve initial dissociation of the oxygen. Instead, reductive elimination is calculated to occur directly from the four-coordinate complex in concert with a lengthening of the Pd–O bond. To investigate this effect experimentally, a four-coordinate Pd­(II) anilido complex containing a flexible, aliphatic linker between the P and O atoms was synthesized. Reductive elimination from this complex was faster than that from the analogous complex containing the more rigid, aryl linker. The flexible linker enables full dissociation of the ether ligand during reductive elimination, leading to the faster reaction of this complex

Reductive Elimination from Phosphine-Ligated Alkylpalladium(II) Amido Complexes To Form sp³ Carbon–Nitrogen Bonds

We report the formation of phosphine-ligated alkylpalladium­(II) amido complexes that undergo reductive elimination to form alkyl-nitrogen bonds and a combined experimental and computational investigation of the factors controlling the rates of these reactions. The free-energy barriers to reductive elimination from <i>t</i>-Bu₃P-ligated complexes were significantly lower (ca. 3 kcal/mol) than those previously reported from NHC-ligated complexes. The rates of reactions from complexes containing a series of electronically and sterically varied anilido ligands showed that the reductive elimination is slower from complexes of less electron-rich or more sterically hindered anilido ligands than from those containing more electron-rich and less hindered anilido ligands. Reductive elimination of alkylamines also occurred from complexes bearing bidentate P,O ligands. The rates of reactions of these four-coordinate complexes were slower than those for reactions of the three-coordinate, <i>t</i>-Bu₃P-ligated complexes. The calculated pathway for reductive elimination from rigid, 2-methoxyarylphosphine-ligated complexes does not involve initial dissociation of the oxygen. Instead, reductive elimination is calculated to occur directly from the four-coordinate complex in concert with a lengthening of the Pd–O bond. To investigate this effect experimentally, a four-coordinate Pd­(II) anilido complex containing a flexible, aliphatic linker between the P and O atoms was synthesized. Reductive elimination from this complex was faster than that from the analogous complex containing the more rigid, aryl linker. The flexible linker enables full dissociation of the ether ligand during reductive elimination, leading to the faster reaction of this complex

Nucleophilic Deoxyfluorination of Phenols via Aryl Fluorosulfonate Intermediates

This report describes a method for the deoxyfluorination of phenols with sulfuryl fluoride (SO₂F₂) and tetramethylammonium fluoride (NMe₄F) via aryl fluorosulfonate (ArOFs) intermediates. We first demonstrate that the reaction of ArOFs with NMe₄F proceeds under mild conditions (often at room temperature) to afford a broad range of electronically diverse and functional group-rich aryl fluoride products. This transformation was then translated to a one-pot conversion of phenols to aryl fluorides using the combination of SO₂F₂ and NMe₄F. Ab initio calculations suggest that carbon–fluorine bond formation proceeds via a concerted transition state rather than a discrete Meisenheimer intermediate

Developing Efficient Nucleophilic Fluorination Methods and Application to Substituted Picolinate Esters

This report describes nucleophilic fluorination of 3 and 5-substituted picolinate ester substrates using potassium fluoride in combination with additive promoters. Agents such as tributylmethylammonium or tetraphenylphosphonium chloride were among the best additives investigated giving improved fluorination yields. Additionally, the choice of additive promoters could influence the potential formation of new impurities such as alkyl ester exchange. Other parameters explored in this study include additive stoichiometry, temperature influence on additive degradation, solvent selection, product isolation by solvent extraction, and demonstration of additive recycling