Study On Friedel-Crafts Alkylation Reaction Of N,O-Acetals With Indoles

In the field of modern organic synthesis,scientists have been pursuing efficient and concise chemical synthesis methods to build the core skeleton of natural products.Among these methods,N-acyliminium ion have a wide range of applications for the construction of carbon-carbon bonds and carbon hybrid bonds.As an important active intermediate,N-acyliminium ion is involved in nucleophilic substitution reaction in the synthesis and application of many complex natural products.At the same time,as part of the essential amino acid(tryptophan),indole skeleton is not only found in numerous natural product molecules and alkaloids,but also a key structural component of many value-added chemicals.Therefore,it is of great significance to develop an efficient and simple method of organic synthesis based on N-acyliminium ion activated indole skeleton.The Paper designed and synthesized six different types of N,O-acetal: N,O-acetal 2-6,N,O-Acetal 2-16,N,O-Acetal 3-5,N,O-Acetal 3-17,N,O-Acetal 4-10,N,O-Acetal 4-21.The following Friedel–Crafts alkylation reactions were investigated catalyzed by lewis acid(silver hexafluoroantimonate)at room temperature.1.Reactants: N,O-acetal(1eq.)and indole(1eq.),catalyst: silver hexafluoroantimonate,Solvent: dichloroethane,the reaction was carried out at room temperature for 12 hours.The asymmetric Friedel-Crafts alkylation reactions of 2-6 and 2-16 with indoles were explored.25 substrates were screened,the selectivity ranged from 65:35 to 99:1,and the yields ranged from 30% to 94%.2.Reactants: N,O-acetal(1eq.)and indole(1eq.),catalyst: silver hexafluoroantimonate(0.1eq.),solvent: dichloroethane,the reaction was carried out at room temperature for 12 hours.The asymmetric Friedel-Crafts alkylation reactions of 3-5 and 3-17 with indoles were explored.11 substrates were screened,the selectivity ranged from 91:9 to 99:1,and the yields ranged from 49% to 90%.3.Reactants: N,O-acetal(1eq.)and indole(1eq.),catalyst: silver hexafluoroantimonate(0.2eq.),solvent: dichloroethane,the reaction was carried out at room temperature for 12 hours.The asymmetric Friedel-Crafts alkylation reactions of 4-10 and 4-21 with indoles were explored.10 substrates were screened,the selectivity ranged from 54:46 to 99:1,and the yields ranged from 53% to 82%.In conclusion,under the catalysis of silver hexafluoroantimonate at room temperature,different types of N,O-acetal formed N-acyliminium ion intermediates have a wide range of suitability for the activation of different types of indole,and the yield and selectivity of the reaction are also pretty.