Study On Transition-Metal-Catalyzed C(sp~3)-H Bond Amination Reactions

Transition metal catalyzed reaction is one of the very effective synthesis method tosynthesize natural organic molecules and a variety of drug molecules, as well as an importantresearch area in organic synthesis chemistry. The activation and functionalization of C–H bondwhich catalyzed by transition metal meet the requirements of the core content of greenchemistry-“atom economy” and exhibit superior competitiveness; Simultaneously, theactivation and functionalization of C–H bond provide new ideas for strategy of retrosyntheticanalysis in traditional organic synthesis, which become the research focus in organicmethodology in recent years.Amine compounds are common in natural products with biological activity andartificially-synthesized compounds,90%of drugs contain one nitrogen atom at least, and theformation of carbon-nitrogen bond is related to about every six reaction in pharmaceuticalindustry. Therefore, develop synthesis method for transforming carbon-hydrogen bonds intocarbon-nitrogen bond directly and meet the requires of green chemistry and atom economy isan important research direction, and is of great significance in pharmaceutical and the otherindustries.Benzylamine is an important structural unit in many drugs, however, it is difficult to obtainit from simple raw materials directly according to viewpoint of synthesis. The rapiddevelopment of the direct amination of benzyl hydrocarbon is benefited from the discovery ofmetal nitrene. The selectivity of amination is greatly improved due to using nitrene stabilizedby metal as nitrogen source, which compares to the high activity free nitrene. In these reactions,the selectivity of benzyl secondary carbon is greater than that of primary carbon which isdetermined by electronic factors. Therefore, to achieve high selective amination of benzylmethyl of toluene derivatives, especially, to achieve selective amination which the selectivity ofbenzyl primary carbon if greater than that of secondary carbon is a challenging research topic,and is also an important application topic for the development and utilization of toluene, xyleneand other basic chemical raw materials.Aim at this project, we detailed analyse the internal relations between the activity andselectivity of the reaction. And based on the achievement of direct amination of aromatichydrocarbon in our previous work, selective amination which the selectivity of benzylsecondary carbon is greater than that of primary carbon is achieved by choosingN-fluorobenzeneimide(NFSI) with large volume and moderate reactivity as nitrogen sourceand using inexpensive copper catalyst. And the direct amination of C–H bond of benzyl oftoluene derivatives is developed. The diamination of the xylene, trimethylbenzene and the other multi-methyl benzene is realized for the first time, and open up a new way for directamination of C–H bond with high efficiency and high selectivity.On the basis of the high selective amination of the above toluene derivatives C(sp~3)–Hbond, in this thesis, palladium catalyzed methyl ketone carbonyl α-C(sp~3)–H bond and thefirst example of high efficient amination of N-fluorobenzeneimide are achieved, and the directamination reaction of acetone is also successfully expanded.