Asymmetric Friedel-crafts Alkylation Reactions Of N-Boc-propargyl Imines With Indoles

Structural reaction of C-C bond is the most common reaction in organic synthesis,Friedel-Crafts reaction is one of the most effective methods connected with the aromatic C-C bond.And the construction of indole heteroatom polycyclic structure exists widely in natural products with biological activity and drug molecules and thus the synthesis containing indole polycyclic structure is very important for the research and development of chiral drug potential.In this thesis,we expound that organocatalytic asymmetric Friedel-Crafts alkylation reaction of propargyl imine in situ generation from C-alkynyl N-Boc-protected N,O-acetals with indole by chiral phosphoric acids catalysts,and synthesis of a class of indoles derivatives with multiple functional groups.In the first part of this thesis,Friedel-Crafts reaction is described as well as a detailed description of relevant reports on the Friedel-Crafts reaction that catalyzed by organic small molecules in recent years.This part mainly introduces the different electrophilic receptor.The second part introduces the chiral phosphoric acids catalyze asymmetric Friedel-Crafts alkylation reaction between propargyl imine in situ generation from C-alkynyl N-Boc-protected N,O-acetals and indole.We achieve excellent yield(81%)and high enantioselectivity(up to 87%ee),when the reaction proceeded in acetonitrile with 5 mol%catalyst and 4A molecular sieve as additive and reaction of 6h at room temperature.In summary,we have explored a reasonable method to get the asymmetric Friedel-Crafts alkylation reaction between propargyl imine in situ generation from C-alkynyl N-Boc-protected N,O-acetals and indole derivatives,which provides a new synthetic method for the syntheis of chiral indole derivatives with multiple functional groups.