Rerouting nucleophilic substitution from the 4-position to the 2- or 6-position of 2,4-dihalopyridines and 2,4,6-trihalopyridines: the solution to a long-standing problem.

2,4-Difluoro-, 2,4,6-trifluoro-, and 2,3,4,6-tetrafluoropyridine undergo nucleophilic substitution preferentially if not exclusively at the 4-position. However, after the introduction of a trialkylsilyl group at C-3 or C-5, the halogen at the 6-(2-)position is displaced selectively. This synthetically valuable regiocontrol can also be realized with other halopyridines such as 2,4-dichloro- and 2,4,6-trichloropyridine.

[1]  M. Schlosser,et al.  Recommendable Routes to Trifluoromethyl‐Substituted Pyridine‐ and Quinolinecarboxylic Acids , 2003 .

[2]  M. Schlosser,et al.  Creating Structural Manifolds from a Common Precursor: Basicity Gradient‐Driven Isomerization of Halopyridines , 2002 .

[3]  M. Schlosser,et al.  Regiochemical Flexibility: The Optional Functionalization of 2,3,5‐Trihalopyridines at the 4‐ or 6‐Position , 2001 .

[4]  M. Schlosser,et al.  Strategies for the Selective Functionalization of Dichloropyridines at Various Sites , 2001 .

[5]  V. I. Krasnov,et al.  Perfluorozinc aromatics by direct insertion of zinc into C–F or C–Cl bonds , 2000 .

[6]  Sergey S. Laev,et al.  Reductive dehalogenation of polyfluoroarenes by zinc in aqueous ammonia , 1997 .

[7]  W. Jondi,et al.  Reaction of octafluorotoluene, 3,5-dichlorotrifluoropyridine, 3-chlorotetrafluoro-yridine and tetrafluoropyrimidine with alkali-metal oximates , 1996 .

[8]  W. Jondi,et al.  Reaction of pentafluoropyridine with lithium hydrazonides; competing monosubstitution at the 2- and 4-positions , 1996 .

[9]  M. Mittelbach.  An Easy and Convenient Synthesis of 6-Methyl-4(1H )-pyridone-3-carboxylic Acid , 1988 .

[10]  V. M. Vlasov,et al.  Interaction of pentafluoropyridine with 4-nitrophenol and pentafluorophenol in the presence of potassium fluoride and 18-crown-6-ether , 1982 .

[11]  I. Collins,et al.  Polyhalogeno-aromatic compounds. Part XVI. The preparation and reactions of polyhalogenophenyl- and polyhalogenopyridyl-hydrazines , 1971 .

[12]  R. Banks,et al.  93. Heterocyclic polyfluoro-compounds. Part IV. Nucleophilic substitution in pentafluoropyridine: the preparation and properties of some 4-substituted 2,3,5,6-tetrafluoropyridines , 1965 .

[13]  R. Chambers,et al.  926. Polyfluoroheterocyclic compounds. Part V. Catalytic reduction of perfluoro- and chlorofluoro-pyridines and the preparation of polyfluoropyridinecarboxylic acids , 1965 .

[14]  C. Tamborski,et al.  Preparation and Reactions of Hydrazino Perfluoroaromatic Compounds , 1964 .

[15]  R. Chambers,et al.  722. Polyfluoro-heterocyclic compounds. Part II. Nucleophilic substitution in pentafluoropyridine , 1964 .

[16]  A. Parkinson,et al.  966. Polyfluoroarenes. Part V. Pentafluorophenylhydrazine and the pentafluorophenyl radical , 1962 .

[17]  M. Stacey,et al.  350. Aromatic polyfluoro-compounds. Part IV. The reaction of aromatic polyfluoro-compounds with nitrogen-containing bases , 1960 .

[18]  O. Seide,et al.  Über den Oxydationsverlauf bei primären Hydrazinen. I. Mitteilung: Die Umsetzung primärer aromatischer Hydrazine mit Schwermetallsalzen , 1933 .