Studies On Preparation And Synthetic Applications Of 3-diazoindolin-2-imines

Indole and its derivatives play an important role in drug chemistry and material chemistry.Therefore,the synthesis of indoles has been the frontier and hot field in organic synthesis chemistry.3-Diazoindolin-2-imines are a new type of diazo reagents developed by our research group.3-Diazoindolin-2-imines can be used as metal-carbenes precursors.We can synthesize various indole ring compounds succinctly and efficiently by using 3-diazoindolin-2-imines as the substrate.In this article,the preparation and application in the construction of indole ring compounds of 3-diazoindolin-2-imines were studied,the main contents and results are as follows:1.A practical and simple method for the preparation of 3-diazoindolin-2-imines was developed.3-Diazoindolin-2-imines were constructed from indoles and sulfonylazides via an electronically matched 1,3-dipolar cycloaddition with wide substrate scope.The startingmaterials were easily accessible and the operation of this reaction was very easy.This reaction was catalyst-free and the reaction conditions were mild.Moreover,the reaction can be expanded to the gram level with high yield,the separation of 3-diazoindolin-2-imines was very convenient.2.A new method was developed for the synthesis of 2,3-diaminindoles with the reaction of 3-diazoindolin-2-imines and secondary amines using rhodium(?)catalyst.In this reaction,3-diazoindolin-2-imines reacted with rhodium catalyst to form a-amidino rhodium carbene intermediate.The insertion of a-amidino rhodium carbene into the N-H bond of secondary amines resulted in the formation of 2,3-diaminindoles.Under the action of oxygen,some of the 2,3-diaminoindoles could transform into imidazo[4,5-b]indoles by oxygen-oxide coupling/desulfonyl reactions.3.A rhodium(II)-catalyzed reaction of 3-diazoindolin-2-imines and tertiary amines was developed and the selectivity of the reaction was related to the type of tertiary amine.When the tertiary amine was allylamine,the reaction was formed by rhodium carbeen formation,C-N coupling and 1,2 or 2,3-migration cascade process,which afforded 3-aryl-2-aminoindoles,3-allyl-3-amino-2-iminoindolines in good yield.When the tertiary amine was proparylamine,the reaction underwent a rhodium carbene formation,C-N coupling and 6-endo-dig cyclization process,which afforded tetrahydro-[1,4]diazepino[2,3-b]indoles in good yield.4.A new method was developed for the synthesis of 5H-pyrazino[2,3-b]indoles through the rhodium(II)-catalyzed reaction of 3-diazoindolin-2-imines and primary amines.Firstly,the rhodium carbene was formed.Then,the rhodium carbene reacted with primary amine enamines to form 2,3-diaminindoles.Finaly,2,3-diaminindoles were transformed into 5H-pyrazino[2,3-b]indoles.5.A rhodium catalyzed formal cycloaddition of 3-diazoindolin-2-imines with a series of 3-(bromoalkyl)-indole compounds was studied.It was found that the 3-diazoindolin-2-imines generated rhodium carbenes reacted with 3-(2-bromoethyl)-indoles,3-(3-bromopropyl)-indoles,3-(4-bromobutyl)-indoles.to form seven-membered rings,eight-membered rings,nine-membered rings by formal[4+3]cycloaddition,formal[5+3]cycloaddition,formal[6+3]cycloaddition,this reaction involved a cascade 3-rhodo-indolin-2-imines formation/C-C coupling and intramolecular SN2 reaction.Respectively,the reaction provided a new method for the synthesis of 5H-azepino[2,3-b:4,5-b]diindoles,azocino[2,3-b:4,5-b']diindoles,5H-azonino[2,3-b:4,5-b']diindoles.6.A new method was developed for the synthesis of spiro[indoline-3,2'-oxazolidin]-2-imines with the reaction of 3-diazoindolin-2-imines and 2-(phenylamino)ethanols using Cu catalyst.The reaction proceeded via copper carbene formation,C-N coupling and C-O coupling cascade process to afford spiro[indoline-3,2'-oxazolidin]-2-imines.The sulfonyl group of spiro[indoline-3,2'-oxazolidin]-2-imines could be readily removed by treating with NaOH to provide spiro[indoline-3,2'-oxazolidin]-2-ketones.When the optically pure chiral 2-(phenylamino)ethanols was used as the substrate,the reaction had a high diastereoselectivity.7.A copper-catalyzed reactions of 3-diazoindolin-2-imines and tryptophols was studied.The reaction involved copper carbene formation,C-C coupling and C-O coupling cascade process,which afforded spiro[indoline-3,1'-pyrano[3,4-b]indol]-2-imines.This reaction provided a simple and efficient way to construct new indole heterocycles.