Copper-catalyzed Hydrogen Transfer Of Nitrogen Heterocyclic Compounds

In this paper,the research progress of oxazaborolidine,the application and research progress of tetrahydroquinoline compounds are reviewed.We have designed a method for transfer hydrogenation reduction of quinoline compounds and other N-Heteroaromatics using oxazaborolidine complex as the hydrogen source.The conditions of hydrogen source,catalyst,solvent,temperature and reaction time were screened by using 2-methylquinoline as template substrate,and the optimal condition was obtained.Ethanolamine was used as the hydrogen source precursor.The ratio of ethanolamine to borane tetrahydrofuran complex is 1:2.Copper perchlorate hexahydrate(20 mol%)was used as the catalyst.The reaction time is 24 hours and the reaction temperature is 40?.The yield of 2-methyl-1,2,3,4-tetrahydroquinoline was as high as 94%.Then,a series of substrates were selected to examine the universality of this method.The experimental results show that the method has good universality for substrates with electron-withdrawing groups,electron-donating substrates and large sterically hindered groups.This transfer hydrogenation process achieves high yields for more than 30 substrates,According to the designed experimental and deuterated experimental results,the structure of oxazaborolidine was confirmed and the plausible e mechanism was proposed.An enlarging experiment was carried out to verify that the method is not limited to the milligram-level reaction and is equally applicable to the gram-level reaction.This method was successfully applied to the synthesis of natural products(±)-Angustureine and(±)-Galipinine.The natural product molecules with medicinal effects were synthesized in three steps with high yield.It is verified that this transfer hydrogenation reduction method has potential value.The possibility of this method for asymmetric transfer hydrogenation was studied.The optimal condition is that the hydrogen source precursor is(1S,2R)-(-)-cis-l-amino-2-nonanol,the catalyst is copper Cu(ClO4)2·6H2O(20 mol%),the solvent is ethyl acetate,and the reaction temperature is room temperature.The yield was 83.3%and the ee of the product was 21.7%.The feasibility of asymmetric transfer hydrogenation in this method was confirmed.This method expands the application of the CBS,so that oxazaborolidine is not limited to the asymmetric hydrogenated reducing ketone compounds and the Diels-Alder reaction.The inexpensive copper-catalyzed transfer hydrogenation to quinoline compounds and other N-Heteroaromatics has been successfully achieved.