Asymmetric Construction Of Continuous Chiral All-carbon Quaternary Carbon Centers Via NHC-catalyzed [3+2] Cyclizations

Indole spiro compounds are ubiquitous core structures in many natural products and drug molecules,and often have important biological activities.Among them,the construction of indole spiro compounds with multiple stereocenters is known as a major synthetic challenge in natural product and drug synthesis.Therefore,great efforts have been devoted to developing novel and efficient strategies to synthesize such compounds with high enantioselectivity.In recent years,nitrogen-heterocyclic carbene(NHC)organocatalysis has received great attention.Asymmetric synthesis of numerous carbocyclic and heterocyclic compounds can be achieved through NHC-catalyzed asymmetric cyclization reactions.Based on the unique catalytic activation characteristics of NHC,we investigated the construction of spirocyclic indolones with two consecutive chiral quaternary carbon centers using NHCcatalyzed [3+2] cyclization.The content of this paper mainly includes the following aspects:In the first part,the development history of nitrogen-heterocyclic carbene is described,and the research progress in the synthesis of indole-based organic frameworks catalyzed by NHC in the past decade is summarized and analyzed,and a comprehensive overview of NHC in the preparation of biologically active indole-based compounds is presented.for outstanding contributions in the NHC,and discusses the current limitations and future prospects of the NHC.The second part describes two strategies for the rapid construction of quaternary carbon chiral centers by NHC-catalyzed cyclization reactions.The efficient asymmetric construction of all-carbon chiral quaternary carbon centers is a long-standing challenge in organic chemistry.In this regard,our research work is divided into two parts,one part is the efficient asymmetric construction of bis-spirocyclic indolones by the [3+2] cyclization reaction between alkenals and isoindigo catalyzed by nitrogen heterocyclic carbene;Part of it is the efficient asymmetric synthesis of bis-spiro-indolinone by the [3+2] cyclization between α-bromocinnamaldehyde and bis-indolinone catalyzed by nitrogen-heterocyclic carbene.These two parts of work use chiral nitrogen heterocyclic carbene as a catalyst to realize the efficient asymmetric construction of two consecutive chiral quaternary carbon centers through two different reaction pathways through the activation of different aldehydes.