Theoretical Study On Iron(?) Tandem Catalyzed Polysubstituted Amines Alkylation Of ?-phenylstyrene

Alkene compounds have the advantages of cheap and easy availability,simple synthesis steps,and efficient utilization of atoms.They are important raw materials and intermediates in organic synthesis,and their catalytic transformations have always attracted attention.Among them,the reaction that catalyzes the C-H bond functionalization of alkenes and retains the double bond is widely used in the synthesis of natural molecules,drugs,etc.Compared with the addition reaction of alkenes,this kind of C-H bond substitution reaction preserves the unsaturation of alkenes in the products,which provides the possibility of tandem reactions.Aza-Prins,an important name reaction in organic synthesis,can retain the carbon-carbon double bond of alkene during amine alkylation,which makes the tandem polysubstituted amines alkylation of alkenes feasible.The C-H bond conversion strategy of alkenes can be well used in the synthesis of unsaturated nitrogen heterocyclic natural molecular compounds.It is very important to devote to the development of multiple C-H substitution reactions in simple alkenes to obtain complex unsaturated components.In this paper,density functional theory calculations have been performed to investigate the reaction mechanism on polysubstituted amines alkylation of ?-phenylstyrene catalyzed by Fe(OTf)3.Bis(tosylamido)methane is activated by Fe(OTf)3 to form tosylformaldimine and its Fe(OTf)3-adduct,electrophile R1 attacks the atomic C1 in ?-phenylstyrene to form allylamide.Considering the competition between N1 and C2 sites in allylamide,we performed electrostatic potential analysis and natural population analysis and further predicted two competitive reaction pathways.According to the calculation results,N1 is a more vulnerable site to electrophilic attack than C2.In addition,we analyzed the activation energy barriers and reaction energies of the entire reaction,and the results showed that the optimal path for this reaction consists of five components:(1)Tosylformaldimine and its Fe(OTf)3-adduct is released from bis(tosylamido)methane;(2)Intermolecular aza-Prins reaction between Fe(OTf)3-tosylformaldimine and ?-phenylstyrene to form allylamide;(3)Condensation of allylamide and Fe(OTf)3-tosylformaldimine;(4)The condensation product completes the homologation reaction;(5)Hexahydropyrimidine derivatives is synthesized through intramolecular reaction.In addition,we also give two parts of the possible reaction pathway for the conversion of 1,3-diamine derivatives to hexahydropyrimidine derivatives: condensation and cyclization reactions.This work will provide insight into transition metal tandem-catalyzed polysubstituted amines alkylation of alkenes with retained double bonds.