Regioselective Amination On The ?,? And ?-positions Of Amides

C-N bonds are widely found in natural products and drug molecules.In organic synthesis,C-H amination and coupling reactions are used to efficiently construct C-N bonds.The existing problems of coupling reactions are the prefunctionalization of the substrate,high reaction temperature and too many by-products.The study on direct C-H amination will improve those problems,the direct C-H amination reaction has the advantages of wide application of substrates,high atomic economy and simple operation.Diazene dicarboxylates,as amination reagents,are widely used in amination reaction due to their cheapness,safe operation and stability in the air.In this paper,diazene dicarboxylates were used as the nitrogen source.Under different catalytic conditions,the regioselective C-H amination reactions on the?,?and?-positions of amides were studied.The first part:the amination reagents were classified according to the sp² and sp³hybrid forms of nitrogen atom,and the reactions touching upon these amidation reagents are summarized.The second part:?-amination reaction of amides with diazene dicarboxylates are studied when Pd?OAc?₂ as catalyst,AgOTf and PivOH as additive,and toluene as solvent.The yield is up to 95%at the optimal conditions.In addition,the amination products are used to synthesize corresponding?-amino acid ester at refluxed HCl/MeOH solution.The third part:the regioselective amination of?,?-unsaturated amides diazene dicarboxylates are realized at different catalytic reaction conditions.?-Amidation products are obtained at the function of zinc salt and N,N-diisopropyl ethylamine.Moreover,?-amination products are gained with excellent yield and regioselectivity in silver salts and tetramethylguanidine conditions.Then,the?-amination products are converted to?-amino acid ester,which provides a new method for the synthesis of such compounds.In summary,we have developed a versatile system for?,?and?-amination reactions of amides.This affords straightforward and effective method for the construction of the?and?-amino acid esters,which will significantly contribute to the direct synthesis of such compounds.