Functionalization Of C-H Bond With Organozinc Reagents

The functionalization of C-H bond is one of the hot topics in organic chemistry,and it has the advantages of environment protection and atom economy.On the other hand,organozinc reagents have good stability and excellent functional group compatibility.However there have fewer reports about using organozinc reagents in metal-free catalyzed C-H bond activation reactions.It is of great value and significance to develop a transition metalfree-catalyzed C-H bond functionalization reaction using organozinc reagents.The oxidative coupling reaction of tetrahydroisoquinoline with aryl zinc reagent was studied.The reaction conditions were optimized and the reaction activity of the organic zinc reagent was investigated.It was found that the aryl zinc reagents prepared by the reaction of halogenated aromatic hydrocarbons with magnesium,zinc chloride and lithium chloride had higher activity and smoothly reacted with 2-phenyltetrahydroisoquinoline providing the desired products in higher yields.In this thesis,organozinc reagents containing a variety of sensitive substituents was prepared,and then C-H functionalization was carried out with2-phenyltetrahydroisoquinoline in the presence of PIFA,the yields of the product was53%-86%.The compatibility of the reaction with the reactive functional group was investigated,and the scope of the tetrahydroisoquinoline derivatives was investigated p-methoxyphenyl protected tetrahydroisoquinoline derivatives can react well with aryl zinc reagents under similar conditions.For tetrahydroisoquinolines protected with benzyl and p-methoxybenzyl groups,a higher temperature and the solvent 1,2-dichloroethene were required.The oxidation of THIQs with N-benzyl protecting grops with PIFA was conducted in DCE within 2 hours at 80?,and subsequent reaction with aryl zinc reagents at room temperature afforded the conesponding products.The C-H bond functionalization of isochroman and benzylic ethers with organozinc reagents was studied.It was found that in the presence of DDQ,isochroman reacted with various aryl zinc reagents,affording the conesponding C-H bond functionalization products in64%-94%yields.In addition,the reaction of isochroman with benzyl and alkyl zinc reagents was studied,and the direct coupling reaction of C(sp~3)-H with these functionalization organiczinc reagents were successfully achieved in the yields of 36%-81%.Finally,the compatibility of the C-H bond with an ester group was studied.Both the tetrahydrocisoquinolines and the isochroman were able to react an organozinc reagent bearing an ester group.The corresponding products were obtained in the yields of 33%-68%.In this paper,a catalyst-free C-H bond functionalization of tetrahydroisoquinoline derivatives and isochroman with organozinc reagents were developed,and a series of organic compounds with potential bioactivity were prepared.The reaction could be performed under mid conditions,and this transformation has excellent compatibility with various sensitive functional groups such as an ester group.