Heterocyclic aromatic hydrocarbons are widely present in various functional molecules such as medicines, pesticides and natural products. Structural modification and functional conversion of heteroatoms in heterocyclic aromatic hydrocarbons are hot topics in the field of organic synthesis. For example, the hetero atom nitrogen contained in the ruthenium and pyrrole structure can be reacted with a ketone compound to form an N,O-acetal structure. However, how to control the stereoselectivity in the synthesis of N, O-acetal compounds is a very challenging subject. To date, asymmetric synthesis of N,O-acetal compounds has been reported in a small number of successful applications in the field of transition metal and chiral phosphonic acid catalysis.

The nitrogen heterocyclic carbene (NHC) catalyst has developed rapidly in the past two decades. It has a unique activation mode and strong catalytic performance, and has become one of the most mature and reliable methods in the field of asymmetric catalysis. In previous work, NHC catalysts were mainly used to activate carbon atoms in carbonyl and imine molecules (Fig. 1a); there have been few reports on the activation and asymmetric transformation of heteroatoms in compounds. Recently, Professor Jin Zhichao of the State Key Laboratory of Green Pesticides and Agricultural Bioengineering of Guizhou University and the Key Laboratory of the Ministry of Education reported the electrophilic activation of aromatic N atoms catalyzed by NHC.

The authors used 吲哚-2-carbaldehyde as the starting substrate and first formed acylazolium intermediate I under oxidizing conditions with NHC catalyst. The NH group in the intermediate I aromatic ring system protonates under the action of a base to form aza-fulvene intermediate II. Subsequent intermediate II acts as a nucleophile with a [3+2] cyclization reaction with an electron-poor ketone substrate to form an N,O-acetal product (Fig. 1b).

The reaction substrate has good universality, and the nucleophilic substrate can be expanded into a plurality of substituted types of indole-2-carbaldehyde and pyrrole-2-carbaldehyde, and the electrophilic substrate can include various types of substituted isatin and α- The ketoester has a reaction yield of up to 99%, and most of the chiral N,O-acetal products prepared can obtain an er value of >95:5. Part of the reaction and product structure are shown in the figure below (Figure 2).