Mild Addition of Nucleophiles to Pyridine-N-Oxides

Abstract

A general and facile one-pot procedure for the synthesis of 2-substituted pyridines from the corresponding pyridine-N-oxides and nucleophiles is presented as a mild alternative to S(N)Ar chemistry. A variety of nucleophiles and heterocyclic-N-oxides participate effectively in this transformation, which uses the phosphonium salt, PyBroP, as a means of substrate activation.

Synthesis and Characterization of a Tetrapodal NO44–Ligand and Its Transition Metal Complexes

“…Retrosynthetically, the most direct way to achieve oxygen donors at positions matching those of the pyridine nitrogen atoms in PY5Me 2 is to connect two malonate functional groups to the central pyridine. A review of potential routes revealed three methods most amenable to this aim: (i) activation of pyridine-N-oxide with the phosphonium salt PyBroP, 27 (ii) synthesis of a linear 1,5-dicarbonyl precursor with subsequent oxidation to a pyridine ring, 28 or (iii) a copper-catalyzed Ullman-type reaction with 2,6-dibromopyridine. 29 Although we were able to add a single malonate unit to pyridine-N-oxide with PyBroP, a second addition was not observed upon further reaction of the monosubstituted pyridine-N-oxide intermediate under the same conditions.…”

Regioselective Reaction of HeterocyclicN-Oxides, an Acyl Chloride, and Cyclic Thioethers

“…We initially examined eucalyptol which gave the product in 26% isolated yield (entry 5). We also examined a series of acyclic ethers with different steric demands (entries [6][7][8][9]. From this study, diisopropyl ether emerged as the most effective solvent which was easy to handle at the operating temperature of the reaction (entry 9; 53%).…”

“…Using the strained cyclohexene sulfide (entry 1) and thiirane (entry 2), the product from the transformation was the 4-nitrobenzoate 3. With less strained 5-and 6-membered ring sulfides as substrates the product was the corresponding chloride 4 (entries [5][6][7][8]. Using thietane as the substrate gave mixtures of both the 4-nitrobenzoate 3 and the chloride product 4, the ratio of which could be altered by changing the reaction temperature (entries 3 and 4).…”

Construction of pyrazolo[3,4-b]pyridines and pyrazolo[4,3-c]pyridines by ring closure of 3-acylpyridine N-oxide tosylhydrazones

“…13,24–27 One possible way to eliminate this requirement is to take advantage of the electrophilic 2-position of a suitably activated pyridine N -oxide using a strategy (Scheme 2) similar to the Reissert-Henze reaction, 28 an approach which has been employed in the preparation of 2-aminopyridines 29–32 via intermolecular amination of pyridine N -oxide, and also has recently been used to functionalize the 2-position of pyridine through the N -oxide with oxygen, sulfur and carbon nucleophiles. 33 Since the introduction of a halogen to the 2-position of pyridine typically requires prior formation of the N -oxide, 13 this method would also eliminate a step in the formation of 1 and thus be a more efficient route to these compounds.…”