The Oxidative Coupling Reaction Of N,N-disubstituted Hydrazine And Borate Ester Promoted By MnO₂

Hydrazine derivatives have been received extensive attention because of their wide applications in organic synthesis and industry.The targeted trisubstituted hydrazine is challenging to be precisely prepared because of either the similar reactivity or the relatively low activity of the two nitrogens in hydrazine precursor.The former would lead to severe regioselectivity issue while the latter would require harsh reaction conditions.The development of new methods toward their synthesis is of great interest from both theoretical and practical perspectives.A Mn O₂-promoted oxidative coupling process between N,N-disubstituted hydrazine and boronic ester is reported.Mechanistically,1,1-Diazene species is firstly generated on oxidation of hydrazine substrate with Mn O₂ and then interacts with boronic ester to form an intermediate boron-ate complex,which is followed by a migration from boron to nitrogen to forge the C-N bond.More importantly,this method can be applicable to a wide range of boronic esters,and thus various N-alkylations and N-arylations can be readily achieved,which would be otherwise very difficult for the precedent approaches.Mechanistically,the success of this process may attribute to the facile generation of 1,1-diazene and formation of boron-ate complex as well as the feasible 1,2-migration.This method was compatible with 1^o-and 2^o-alkyl boronic esters,it shows that the oxidative coupling process obviously outcompetes the conventional two-step N-alkylation approach which generally require condensation of hydrazines and carbonyls and subsequent reduction by hydride agent.This reaction can also be applied to asymmetric synthesis.A mixture of two diastereomers in a ratio of 1:1 can be obtained by reacting the chiral substrate hydrazine with a racemic borate compound,which can be separated by silica gel column chromatography.This indicates that the reaction is feasible for preparing hydrazine derivatives with a single configuration.Not only that,the formation of3-hydrazineylpropanenitrile and 3-hydrazineylpropanoate products indicate that the reaction would serve as a supplementary to the aza-Michael addition of hydrazine.Interestingly,N,N-disubstituted hydrazine can also react with boronic esters with carbonyl structure to obtain the final coupling product without a condensation reaction to form imines which shows that the reaction has achieved high selectivity during the formation of the product and further confirms the compatibility with carbonyl borate.This method is applicable to the synthesis of structural complex molecules which contain estrone skeleton,indicating the potential access to structural complex drugs or natural products.In general,this reaction can be used to prepare challenging N,N-trisubstituted hydrazine derivatives under mild conditions in an easy-to-operate and simple way.And since hydrazine and borate substrates are readily available on the market or synthetically,we believe that this reaction route can be applied to many research work.