N-Boryl Pyridyl Anion Chemistry.

ConspectusPyridine is a crucial heterocyclic compound in organic chemistry. Typically, the pyridine motif behaves as an N-nucleophile and an electron-deficient aromatic ring. Transforming the pyridine ring into an electron-rich system that exhibits reactivity contrary to classical expectations could unveil new opportunities in pyridine chemistry. This Account describes an approach to the umpolung reactivity of the pyridine ring through the formation of an unprecedented N-boryl pyridyl anion (N-BPA) intermediate that enables new catalysis and transformations.In 2017, we discovered that 4-phenylpyridine acts as an efficient catalyst for the borylation of iodo- and bromoarenes using diboron(4) compounds. Mechanistic studies revealed that the in situ formation of an N-BPA intermediate in the pyridine/diboron(4)/methoxide reaction system is a pivotal step in this transformation. Further investigations showed that N-BPA exhibits dual reactivities as both a strong electron donor and a potent nucleophile. This unique reactivity profile has unveiled novel pathways for redox catalysis, pyridine derivatizations, and umpolung transformations.Based on the electron-donor characteristic of the N-boryl pyridyl anion, we have developed a redox catalytic system mediated by a pyridine catalyst. In the pyridine/diboron(4)/base reaction system, the in situ formation of N-BPA followed by single electron transfer (SET) to a substrate with regeneration of the pyridine molecule establishes a redox catalytic cycle. This approach enables the single-electron reduction of a variety of substrates employing 4-phenylpyridine as a catalyst and diboron(4) as the electron source. Upon visible-light excitation, this intermediate transitions into its excited state, exhibiting significantly enhanced reductivity. This enables the establishment of a modular photoredox system consisting of various pyridine/diboron(4)/base combinations that allow for fine-tuning of its redox property. Using this strategy, we performed a series of challenging single-electron reduction reactions, including the single -electron reduction of nonactivated chloro- and fluoroarenes, and Birch reduction of arenes.The nucleophilic character of the N-boryl pyridyl anion was effectively harnessed to facilitate pyridine derivatization and umpolung transformations. By directly quenching the in situ-generated N-BPA with a proton source, we developed a practical approach to N-H-1,4-dihydropyridines (DHPs). Bimolecular nucleophilic substitution reaction between N-BPA and an alkyl bromide produced a 4-alkyl-1,4-DHP, which subsequently releases an alkyl radical under photoredox conditions. This process enabled a catalytic transformation of alkyl bromides into alkyl radicals. Employing 4-trifluoromethylpyridine in this chemistry, the resulting N-BPA intermediate undergoes elimination of fluoride to yield a 4-pyridyldifluoromethyl nucleophile, which then reacts with electrophiles to realize a defluorinative functionalization reaction to forge pyridyldifluoromethyl compounds. Alternatively, when 4-perfluoroalkylthiopyridine was employed, a similar elimination process occurred to form a perfluoroalkyl anion, demonstrating a novel nucleophilic perfluoroalkylation reagent that offers distinct advantages over traditional reagents.The reactivities of the N-boryl pyridyl anion described in this Account provide new insights into pyridine chemistry. We anticipate that these findings will inspire further exploration of novel reactivities and mechanisms in pyridine and related heterocyclic chemistry.