Asymmetric Catalytic Substitution Of Sulfonamide Groups

In recent years, asymmetric catalysis has become one of research focuses in organic synthetic chemistry and catalytic science. Asymmetric enamine catalysis is used to realize theα-functionalization of carbonyl compounds in organic synthesis. About the cleavage of carbon–nitrogen bonds in asymmetric reaction, more papers have covered nucleophilic addition of carbon–nitrogen double bonds, such as Mannich reaction. However, there is little coverage of asymmetric nucleophilic substitutions of the cleavage of carbon–nitrogen single bonds in the literature. In the reaction mechanism of unimolecular nucleophilic substitution (SN1), it can produce carbocations which can easily lead to the racemization of the products. So, it is of great significance to study the asymmetric SN1 type reaction.To study the asymmetric SN1 type reaction and explore the application of the cleavage of carbon– nitrogen bond in organic synthesis from a new view, we developed a highly enantioselective SN1 type reaction with tosyl-activated benzhydrylamine compounds as electrophiles, which could generate stable carbocations in situ. In the reaction, it could control the attack direction of the enamine intermediate through the modification of the catalyst and the tuning of steric and electronic effects of the activating groups attached to the nitrogen atom.A number of studies indicate that under acidic conditions the carbon– nitrogen bond cleavage can be realized with tosyl-activated benzhydrylamine compounds as substrate which can give stable carbocations. Therefore, the reaction can take place under a mild condition.The asymmetric SN1 type reaction has been developed via carbon– nitrogen bond cleavage to afford carbocations and efficiently synthesize optically active cyclohexanone derivatives. Then, the absolute configuration of the products has been determined by the X-ray diffraction. This method has advantages such as the catalyst can be easily prepared and the experiment is easy to operate. Furthermore, some aldehydes with prochiral center could give products in good to excellent yields. This method can play a vital role in developing more asymmetric reactions via carbon– nitrogen bond cleavage.To study the reaction mechanism, the reactive intermediates have been detected by high resolution mass spectrometer (ESI/HRMS). Mechanistic studies suggested that first, the substrate (ketone) coupled with the catalyst to give iminium ions, which could be easily changed into the enamine tautomer. Next, the enamine intermediate acting as a nucleophile attacked the carbocation which is generated in situ from tosyl-activated benzhydrylamine compounds. At last, in the presence of water, the product was formed, and the catalyst was released to participate in the next catalytic cycle.