New Type Of Cyanation Of Indoles And Asymmetric Hydrogenation Of Acetopheneneo

Aromatic nitrile is an important class of organic synthesis,and it is widely used in many chemicals such as dyes,herbicides,drugs and materials.Indole is a common scaffold in medicinal chemistry.Among them,3-substituted indole plays an important role in the synthesis of various bioactive molecules,3-cyanoindole is a key intermediate in the synthesis of antibacterial,antiviral and cytotoxic natural products such as nortopsentins.Therefore,it is very important to introduce a cyano functional group into the oxime moiety.At present,there are many methods for obtaining cyano groups.With the development of cyanidation reaction,direct cyanation of transition metal-catalyzed aryl C-H bonds has become the most attractive method for synthesizing aryl nitriles.In addition,chiral compounds play an increasingly important role in chemicals such as pharmaceuticals.With the development of chiral compound synthesis methods,the asymmetric reaction catalyzed by asymmetric metal-ligand complexes has become the most popular.A method of synthesizing an asymmetric compound.In the asymmetric catalytic work,the asymmetric hydrogenation of ketone compounds has become the most effective method for the synthesis of chiral alcohol intermediates.In this paper,we used C-H cyanidation method to achieve the preparation of phthalonitrile,and explored the asymmetric hydrogenation of ketone catalyzed by Ru-ligand.The main research contents are as follows:(1)Based on the previous work,this paper uses a non-toxic and friendly electrophilic cyanating reagent N-cyanosuccinimide to achieve direct hydrazine and pyrrole substrate using Lewis acid catalysts.The yield of the cyanation reaction is up to 97%.A series of ruthenium substrates and pyrrole substrates can be smoothly reacted to form 3-cyanoguanidine and 2-cyanopyrrole with excellent regioselectivity.It is worth mentioning that this scheme shows high reactivity to free hydrazine.The reaction system was successfully applied to the gram-level reaction of the two substrates,and the yield was 80% or more.Through the nuclear magnetic experiment and learning from the work of the predecessors,the possible reaction mechanism of the reaction system was explored.(2)According to Noyori's work,the asymmetric complexes of metal-bisphosphine ligand-benzimidazole diazonium ligand complexes can effectively regulate the asymmetric hydrogenation of ketones.We designed and synthesized a series of different Ru-bisphosphine ligand-benzimidazole ligand complexes and their reactivity in asymmetric hydrogenation of ketones were investigated.After screening,the C3 compound performed well,and a series of different types of acetophenone derivatives were tested using C3 compounds,and the reactivity was able to reach intermediate levels.