Reviews and Accounts ARKIVOC 2013 (i) 154-174
4. Amination Yin et al. developed a general and efficient method to convert pyridine N-oxides to 2aminopyridines 23 in a one-pot process in high yields and high regioselectivity. The process used commercially available reagents t-BuNH2 and Ts2O and showed good functional group compatibility (Scheme 9).15 The use of t-BuNH2 was critical for shutting down side reactions such as dimerization and tosylation of the product as well as suppressing the reaction between the amine and the activating reagent Ts2O. TFA treatment of the crude reaction mixture effectively removed the t-Bu group.
Scheme 9
Londregan et al. reported a general and facile one-pot amination procedure for the synthesis of 2-aminopyridines from the corresponding pyridine N-oxides as a mild altermative to SNAr chemistry. The authors found that the phosphonium salt PyBroP (bromotripyrrolidinophosphonium hexafluorophosphate) functioned as a general and mild N-oxide activator for the regioselective addition of amine nucleophiles. In this reaction, unhindered- aliphatic amines participated most effectively in the transformation, but aminations using heterocycles, such as imidazoles and pyrazoles, unexpectedly proceeded (Scheme 10).16 The mechanism of the reaction is shown in Scheme 11. The reaction proceeded via the activated pyridine complex 24. Subsequent basic rearomatization 25 afforded the desired 2-aminopyridine 23 and phosphoryltripyrrolidine 26, the only significant organic byproduct of the reaction. Recently, the same group also found that reactions could be expanded into broader classes of nucleophiles (such as phenol, sulfonamide, malonate, pyridone, thiol) after minimal reaction
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