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

Synthesis of Novel Fluoropicolinate Herbicides by Cascade Cyclization of Fluoroalkyl Alkynylimines

The cascade cyclization of fluoroalkyl alkynylimines with primary amines has been modified to allow the synthesis of 4-amino-5-fluoropicolinates. Use of <i>N</i>-trityl and acetal protecting groups in the cyclization precursor led to 5-fluoropyridines that were easily deprotected to picolinaldehyde derivatives for further elaboration to structures of interest as potential herbicides. This method provided access to picolinic acids with alkyl or aryl substituents at the 6-position that were previously inaccessible via cross-coupling chemistry

Computational and Experimental Studies of Regioselective S_NAr Halide Exchange (Halex) Reactions of Pentachloropyridine

The Halex reaction of pentachloropyridine with fluoride ion was studied experimentally and computationally with a modified ab initio G3MP2B3 method. The G3 procedure was altered, as the anionic transition state optimizations failed due to the lack of diffuse functions in the small 6-31G* basis set. Experimental Halex regioselectivities were consistent with kinetic control at the 4-position. The reverse Halex reaction of fluoropyridines with chloride sources was demonstrated using precipitation of LiF in DMSO as a driving force. Reverse Halex regioselectivity at the 4-position was predicted by computations and was consistent with kinetic control. Scrambling of halide ions between chlorofluoropyridines was catalyzed by <i>n</i>-Bu₄PCl, and the products of these reactions were shown to result from a combination of kinetic and thermodynamic control. Comparison of the C–F and C–Cl homolytic bond dissociation energies suggests that an important thermodynamic factor which controls regioselectivity in this system is the weak C2–Cl bond. The differences between Δ<i>H</i>° values of chlorofluoropyridines can be explained by a combination of three factors: (1) the number of fluorine atoms in the molecule, (2) the number of fluorine atoms at the C2 and C6 positions, and (3) the number of pairs of fluorine atoms which are ortho to one another

Aqueous Suzuki Coupling Reactions of Basic Nitrogen-Containing Substrates in the Absence of Added Base and Ligand: Observation of High Yields under Acidic Conditions

A series of aqueous heterogeneous Suzuki coupling reactions of substrates containing basic nitrogen centers with phenylboronic acid in the absence of added base and ligand is presented. High yields of products were obtained by employing aryl bromides containing aliphatic 1°, 2°, and 3° amine substituents, and good to high yields were obtained by employing a variety of substituted bromopyridines. In the former series, the pH of the aqueous phase changed from basic to acidic during the course of the reaction, while in the latter series the aqueous phase was on the acidic side of the pH scale throughout the entire course of reaction. A mechanistic interpretation for these observations, which generally preserves the oxo palladium catalytic cycle widely accepted in the literature, is presented

NMR Chemical Shifts of Trace Impurities: Industrially Preferred Solvents Used in Process and Green Chemistry

The ¹H and ¹³C NMR chemical shifts of 48 industrially preferred solvents in six commonly used deuterated NMR solvents (CDCl₃, acetone-<i>d</i>₆, DMSO-<i>d</i>₆, acetonitrile-<i>d</i>₃, methanol-<i>d</i>₄, and D₂O) are reported. This work supplements the compilation of NMR data published by Gottlieb, Kotlyar, and Nudelman (J. Org. Chem. 1997, 62, 7512) by providing spectral parameters for solvents that were not commonly utilized at the time of their original report. Data are specifically included for solvents, such as 2-Me-THF, <i>n</i>-heptane, and <i>iso</i>-propyl acetate, which are being used more frequently as the chemical industry aims to adopt greener, safer, and more sustainable solvents. These spectral tables simplify the identification of these solvents as impurities in NMR spectra following their use in synthesis and workup protocols