2-Fluoropyridine-5-boronic Acid

Technical Specifications

Product Description & Scientific Applications

2-Fluoropyridine-5-boronic Acid (6-fluoropyridine-3-boronic acid, 6-fluoro-3-pyridinylboronic acid, 2-fluoro-5-pyridylboronic acid) is an electron-deficient heteroaryl boronic acid generally used as a fluorinated pyridyl building block in medicinal-chemistry, agrochemical, and fine-chemical synthesis. The boronic-acid group is away from the nitrogen, so the compound is relatively less prone to undergo rapid protodeboronation than other compounds featuring the 2-pyridylboronic-acid motif.

This compound may contain small amounts of the cyclic anhydride (boroxine); which have a minor impact on the yield of its subsequent reactions.

Applications and Reactions

• Hydroxydeboronation to fluorohydroxypyridines: aqueous hydrogen peroxide or mCPBA replaces the B(OH)2 group with hydroxyl and retains the C–F bond, giving 2-fluoro-5-hydroxypyridine (6-fluoropyridin-3-ol). Rault and co-workers reported this transformation for halopyridinylboronic acids and esters under mild conditions, regioselectively and without N-oxide formation.
• Suzuki–Miyaura coupling: couples with aryl, heteroaryl, vinyl, and alkenyl electrophiles to give 2-fluoro-5-aryl-, 2-fluoro-5-heteroaryl-, and alkenyl-substituted pyridines. As with other pyridylboronic acids, the pyridine nitrogen can interact with transition-metal catalysts, so palladium source, ligand, base, solvent, and coupling partner strongly affect performance.
• Aromatic SNAr at the 2-position: the ring nitrogen activates the C–F bond at C2 toward aromatic nucleophilic substitution. Amines, alkoxides, phenoxides, thiolates, amides, hydrazines, and stabilised carbanions can displace fluoride under suitable conditions, giving 2-amino-, 2-alkoxy-, 2-thio-, and 2-carbon-substituted pyridines from the coupled product.
• Protected and masked boron variants: the pinacol ester is commercially available (CAS 444120-95-0). Molander and co-workers reported potassium 6-fluoropyridin-3-yltrifluoroborate as a bench-stable Suzuki partner; in their substrate scope, it coupled more efficiently with 4-chlorobenzonitrile than with 4-bromobenzonitrile.

Further Reading

For boronic acids, boronic esters, protodeboronation, boroxine content, and Suzuki–Miyaura reagent selection, see NorrChemica's Lab Journal guide: Choosing Your Boron Source for Suzuki–Miyaura Coupling.

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