Base-catalyzed aryl halide isomerization enables the 4-selective substitution of 3-bromopyridines

Abstract

The base-catalyzed isomerization of simple aryl halides is presented and utilized to achieve the 4-selective etherification, hydroxylation and amination of 3-bromopyridines. Mechanistic studies support isomerization of 3-bromopyridines to 4-bromopyridines proceeds...

Nucleophilic C–H Etherification of Heteroarenes Enabled by Base-Catalyzed Halogen Transfer

“…Merging halogen transfer with a substitution reaction is a critical design feature for an overall high-yielding and selective C–H functionalization reaction . In the absence of a thermodynamic driving force, aromatic halogen transfer is expected to be reversible and unselective while generating N -heteroaryl halides that are prone to undesired side reactions. − A separate challenge for the proposed method is identification of an aryl halide that efficiently transfers a halogen to transient N -heteroaryl anions but does not decompose or undergo nucleophilic substitution under basic conditions.…”

Migratory Aryl Cross-Coupling

“…10 Major contributions were also made by Bandar and coworkers through their investigation of base-mediated "halogen dance" transformations of electron-poor arenes. 11 Further, elegant work by Yamaguchi on aryl ester electrophiles 12 and by Martin with stoichiometric nickel complexes 13 have advanced the concept of metal migration on aromatic rings, and Spokoyny has reported an intriguing cross-coupling of carborane bromides involving a metal "cage-walking" process. 14 Nonetheless, the ideal method would be able to directly engage the traditional reactants of cross-coupling, i.e., aryl halides and nucleophiles, and operate catalytically under mild conditions.…”

K2CO3/18-Crown-6-Catalyzed Selective H/D Exchange of Heteroarenes with Bromide as a Removable Directing Group

“…For comparison, the reaction with KO t -Bu was also tested (Table , entry 9). Despite the achievement of a high atom % deuterium incorporation, an unacceptable low yield was observed due to debromination, a common side reaction under strong base conditions . Replacement of 18-crown-6 with other crown ethers afforded only 13% and 25% deuterium incorporation (Table , entries 10 and 11).…”

“…Despite the achievement of a high atom % deuterium incorporation, an unacceptable low yield was observed due to debromination, a common side reaction under strong base conditions. 16 Replacement of 18-crown-6 with other crown ethers afforded only 13% and 25% deuterium incorporation (Table 1, entries 10 and 11). While 1,10-phenanthroline, 2,2′biimidazole, and cyclohexane-1,2-diol can promote KOt-Buinvolved reactions via the coordination of potassium cation, they are totally ineffective in this K 2 CO 3 -catalyzed H/D exchange reaction (Table 1, entries 12−14).…”