Synthesis Of Indolines Via Intramolecular Unactivated C_sp³-H Bonds Amination

N-heterocycles,are structural motifs that are found in a number of biologically active molecules,has attracted great attention in organic synthesis.Construction of N-heterocycles via C-N bond formation has always attracted great attention in organic synthesis.Ullman reaction and Buchwald-Hartwig amination have been well disclosed to synthesis of N-heterocycles via Csp2-N bond formation.Other than traditional nucleophilic substitutions,the intramolecular Csp3-H bond amination as one of straightforward process for the synthesis of saturated N-heterocycles.The strategy based on the transition-metal catalyzed C-N bond formation has been well established from noble metal to cheap metal.More recently,transition-metal free catalytic system has been proven to be an alternative of these transition-metal mediated reactions.However,there were still remains challenging such as low selectivity,limited feasibility and poor practicability.In this thesis,two efficient methods for the synthesis of indolines through the intramolecular unactivated Csp3-H amination are developed which used iodine as mediating reagent or the copper salt.These two works focuse on the Csp3-H functionalization and provid new way for synthesis of N-heterocycles.The details are as follows:1.An efficient approach of intramolecular unactivated Csp3-H amination for the production of indolines with iodine is disclosed.The advantages of this work are as following:(1)Unactivated Csp3-H bonds rather than Csp2-H bonds were found preferable for the amidation,giving rise to indolines selectively but not carbazoles,offerring a new way to synthesize C-7 arylated indolines.(2)A patent class of indolines could be obtained in high yield.As reported by reference,only a trace amount of product was observed(<1%).(3)Anhydrolycorinone and oxoassoanine derivative have been synthesized from indolines,which have been obtained via iodine system.(4)The gram-scale reactions of two functional indolines were conducted successfully implied that this method could be a good prospect in application.This transition-metal free method provides an efficient straightforward strategy for the synthesis of N-heterocyclic compounds.2.A new copper-catalyzed intramolecular unactivated Csp3-H amination methodology is described.The advantages of this work are as following:(1)It shows good catalytic efficiency in the direct Csp3-N bond formation with various substrates via noble metal free.(2)The catalytic system has special site-selective ability and shows high preference for unactivated Csp3-H functionalization over Csp2-H functionalization,the secondary Csp3-H bond was preferable leading to C-N bond formation.(3)The mechanism was gained more profound knowledge via advanced technology,such as NMR,XPS and Theoretical calculation by Gaussian 03.(4)This transformation can be finished within one hour.Thus,the approach provides a quick and easy strategy for the synthesis of indolines.