Study On Cobalt-Catalyzed Asymmetric Hydroamination And Hydroaromatization Of Alkenes

Alkenes are important industrial products that can be synthesized by simple steps or obtained directly from abundant petroleum.Whereas the unique advantages of radical reaction,such as mild conditions and good compatibility of functional groups.Recently,transition metal-catalyzed alkene radical reactions have been widely developed,which provides an efficient and alternative way for the synthesis of high-value compounds such as pharmaceutical preparations and functional polymers.Cobalt is a kind of catalyst with abundant reserves,cheap,easy availability,abundant valence and excellent biocompatibility.In recent years,cobalt-catalyzed hydrogen atom transfer(HAT)reactions have developed into a versatile platform for the hydrogen functionalization of olefins with excellent chemical,regioselectivity,and functional group tolerance.The radical addition/atom transfer reaction of olefins with a variety of radical match molecules containing C=C/X can be realized by using high-valence cobalt hydrogen mediated HAT reaction.Recently,the coupling reaction of radicals with nucleophiles has also been reported,which has aroused great interest in the highly challenging asymmetric reaction.So far,several efficient intramolecular asymmetric hydrogen functionalization reactions have been reported.In this paper,through the continuous in-depth understanding of such reaction mechanisms,the efficient asymmetric hydroamination and hydroaromatization of olefins with nucleophilic reagents have been created by using ligand design and its coordinated regulation with nucleophilic reagents and oxidants,which provides a new strategy for the construction of C-N and C-C bonds with high enantioselectivity.The specific research contents are as follows:1)Nitrogen containing organic compounds was widely used in pharmaceutical molecules,natural products and organic materials.Hydroamination of olefins is one of the most direct and effective methods to synthesize nitrogen-containing organic compounds.In order to solve the difficulty of stereochemical control of radical hydroamination reaction,this chapter use salen-supported cobalt complex as catalyst,1,1,3,3-tetramethyldisiloxane as hydrogen donor,and N-fluorodiphenyl sulfonimide(NFSI)as both oxidant and nitrogen source,enabling universal radical hydroamination of olefins.This method has excellent substrate application range,including non-activated olefin,aryl ethylene andα,β-unsaturated carbonyl compounds can react smoothly.Asymmetric hydroamination of olefins was carried out using chiral cobalt(salen)catalyst,a series of chiral amines were synthesized with excellent yields and good enantioselectivity.This is the first case of efficient cobalt hydrogen HAT mediated intermolecular asymmetric hydrogen functionalization of olefins.2)The optically active nitrogen heterocyclic skeleton widely exists in natural products and drug molecules.This paper used salen cobalt as catalyst,phenyl silane as hydrogen donor,and N-fluorodiphenyl sulfonimide(NFSI)as oxidant to achieve asymmetric hydroamination of non-activated amino alkenes(up to 99%yield,up to92%ee)under mild conditions.This method effectively overcomes the competitive reaction of two different nitrogen nucleophiles,and at the same time,a series of chiral five-member nitrogen heterocyclic compounds are synthesized with excellent yield and moderate to good enantioselectivity by using nitrogen source design.Mechanistic studies reveal that the key nucleophilic substitution step effectively controls the stereochemistry of the reaction,laying the foundation for the asymmetric control of cobalt hydrogen-catalyzed alkene reactions with nucleophiles.3)Hydroaromatization of(hetero)aromatics with olefins is one of the most simple and efficient methods to construct complex carbon skeletons.Among them,the asymmetric hydroaromatization of indole has attracted much attention due to the importance of indole skeleton in drug molecules.Whereas the problem that the asymmetric hydroaromatization of olefins with indole derivatives often requires the assistance of directing groups,we used the cobalt hydrogen mediated oxidation HAT strategy,using tertbutylbenzoateperoxide(TBPB)and dimethylphenylsilane as oxidants and hydrogen donors,respectively,to realize the asymmetric hydroaromatization of styrene derivatives with indole derivatives without the participation of directing groups.A series of 1,1-di(hetero)aryl alkanes with high enantiomeric excesses(up to 98%yield,up to 99%ee)were synthesized by extending them to other electron rich aromatic hydrocarbons.This is the first case of asymmetric hydrocarbonation of olefins initiated by cobalt hydrogen HAT,which provides an efficient and simple method for the synthesis of chiral(hetero)aromatic compounds with medicinal value.In a word,the asymmetric hydrogen functionalization of olefins with nitrogen nucleophile reagents and carbon nucleophile reagents was realized by Co H-HAT process with cheap and low-toxic metal cobalt as catalyst,under the control of salen ligand and oxidant.The mechanism study showed that the reaction experienced a novel S_N2 like process of alkyl cobalt(IV)cationic intermediate and nucleophiles,which laid a solid foundation for the development of asymmetric coupling reaction of alkyl radicals with various nucleophiles.